presentation on memory loss

Understanding aging brains, how to improve memory and when to seek help

Scientists have identified ways to minimize age-related changes and improve everyday memory function.

• Older Adults and Aging
• Learning and Memory

Memory and aging

Losing keys, misplacing a wallet, or forgetting someone’s name are common experiences. But for people nearing or over age 65, such memory lapses can be frightening. They wonder if they have Alzheimer’s disease or another type of dementia. Developing Alzheimer’s is a widespread fear of older adults.

The good news is that Alzheimer’s disease is not a normal part of aging. Most older adults don’t get Alzheimer’s! Fewer than 1 in 5 people age 65+ and less than half of those age 85+ have the disease. However, it is important to understand that our brains change over time, and it is helpful to be able to distinguish normal changes from those that require medical and psychological attention.

What brain changes are normal for older adults?

Although new neurons develop throughout our lives, our brains reach their maximum size during our early twenties and then begin very slowly to decline in volume. Blood flow to the brain also decreases over time. The good news is that many studies have shown that the brain remains capable of regrowth and of learning and retaining new facts and skills throughout life, especially for people who get regular exercise and frequent intellectual stimulation. Although there are tremendous differences among individuals, some cognitive abilities continue to improve well into older age, some are constant, and some decline.

Some types of memory improve or stay the same

A type of memory called semantic memory continues to improve for many older adults. Semantic memory is the ability to recall concepts and general facts that are not related to specific experiences. For example, understanding the concept that clocks are used to tell time is a simple example of semantic memory. This type of memory also includes vocabulary and knowledge of language. In addition, procedural memory, your memory of how to do things, such as how to tell time by reading the numbers on a clock, typically stays the same.

Some types of memory decline somewhat

Do you sometimes arrive at the grocery store and have trouble remembering what you are there to get? Do you occasionally have trouble remembering where you left your car in the parking lot? Or do you have difficulty remembering appointments such as what time you’re supposed to meet your neighbor for coffee? Episodic memory, which captures the “what,” “where,” and “when” of our daily lives, is to blame. Both episodic and longer term memory decline somewhat over time.

Other types of brain functions that decrease slightly or slow down include:

• information processing and learning something new
• doing more than one task at a time and shifting focus between tasks

Possible causes of memory problems

If you or a loved one is having memory problems that are more bothersome than you would normally expect, don’t assume that Alzheimer’s or another form of dementia is the culprit. Glitches in memory can be caused by many physical and psychological conditions that are reversible. Identify and treat the condition, and your memory will improve! For example, the following common conditions can lead to memory problems:

• Dehydration
• Medication side effects
• Poor nutrition
• Psychological stress
• Thyroid imbalance

It is important to discuss these and other possible causes of memory problems with your medical doctor and to have a complete medical workup. Also, ask to see a psychologist for a complete neuropsychological evaluation to rule out anxiety, depression, or other psychological stresses and to test for cognitive changes.

Tips for maintaining and improving your memory

Here is good news about our aging brains. Scientists have identified ways to minimize age-related changes and improve everyday memory function. Here are some of their tips:

Socialize. Participation in social and community activities improves mood and memory function.

Get moving.  Physical activities and exercise, such as brisk walking, help boost and maintain brain function.

Train your brain. Using mnemonic strategies to remember names improves learning and memory. (Mnemonics are tricks and techniques for remembering information that is difficult to recall: An example is the mnemonic “Richard of York Gave Battle in Vain” to remember the first letters of the colors of the rainbow in order of their wave lengths: red, orange, yellow, green, blue, indigo, and violet.)

Don’t buy into ageist stereotypes about memory decline. Studies have shown that having positive beliefs about aging can improve memory performance in older adults.

It’s difficult to gain knowledge if you can’t see or hear well.  Make sure you wear your prescription glasses or hearing aids if you have them. And have your eyes and hearing tested regularly.

Keep a sense of control and confidence in your memory. Don’t assume that little memory lapses mean you have dementia. Use memory aids to gain and maintain confidence (see Memory Aids on next page).

Avoid distractions that divert your attention. Distractions can range from trying to do several things at once to loud noises in the background. Even your thoughts can distract your attention. For example, if you’re preoccupied with a stressful job or home environment and you’re not paying attention when your friend gives you directions to her new home, you will not be able to recall how to get there.

Memory aids

Keep “to do” lists.

Keep “to do” lists and put them where you will see them often. Mark off items as you accomplish them.

Establish a routine

Establish a routine and follow it. For example, if you take your medicines at the same times every day, you are more likely to remember them.

Don’t rush. Give yourself time to memorize a new name or recall an old one.

Everything in its place

Keep everything in its place: If you always put your reading glasses in the same place, you will always know where they are. Put items that you don’t want to forget in a place where you will see them when you need to. For example, hang your keys by the exit door you use most often.

Use associations

Use associations. For example, picture an apple on top of a gate to recall Mrs. Applegate’s name.

Tag new information

Tag new information by relating it to something that you already know and that is easy to recall. Let’s say you are in your car on the way to the hardware store and you have forgotten to make a list of the five items you need. While you still remember them, relate each item to one of five pieces of furniture in your family room: a shiny new hammer on top of the TV, a role of duct tape on the seat of your favorite chair, and so on. When you get to the store, visualize the five pieces of furniture and their five items.

Keep a calendar

Keep a paper or electronic calendar of important dates. Make sure to check it a couple of times a day.

When to seek professional help

Here is an important tip: Normal memory problems do not affect your everyday living. If you forget where you put your keys, you probably just need to get better organized. However, if you forget what keys are used for or how to unlock doors, you should see a psychologist for a complete assessment and/or speak with your primary health care provider. This type of memory problem is not a normal part of aging.

Other tip-offs that a memory problem may require professional attention include:

• Forgetting how to carry out everyday tasks, such as handling money or paying bills
• Not being able to learn new things, such as how to operate a new microwave or to take an alternate route to the grocery store
• Not recalling the names of loved ones

The memory glitches that occur normally during older age are subtle and do not have to interfere with daily life. In fact, you can easily adapt to them by making lists, establishing routines, using associations, and employing other memory aids.

Alzheimer’s Disease Education and Referral Center P.O. Box 8250 Silver Spring, MD 20907-8250 (800) 438-4380

Alzheimer’s Association 225 N. Michigan Avenue, Suite 1700 Chicago, IL 60611-7633 (800) 272-3900

Eldercare Locator (800) 677-1116

Find a Psychologist

APA Office on Aging Web site

This fact sheet was developed by the APA Office on Aging and Committee on Aging, in cooperation with Elizabeth Vierck, health writer.

Recommended Reading

• Memoria y Envejecimiento (PDF, 240KB)

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Memory loss and dementia

Memory loss is a distressing part of dementia, both for the person with the condition and for the people around them.

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• The emotional impact of living with memory loss
• Therapy and approaches for memory loss support
• Memory loss and dementia – useful organisations

Supporting a person with memory loss

How does memory loss affect a person with dementia.

People with dementia often experience memory loss . This is because dementia is caused by damage to the brain, and this damage can affect areas of the brain involved in creating and retrieving memories.

For a person with dementia, memory problems will become more persistent and will begin to affect everyday life. This can be difficult to cope with, both for the person themselves and for the people around them.

However, there are ways to help a person with dementia manage their memory problems and stay independent for longer. 

Read our free booklet

For straightforward advice and practical tips written directly for the person with memory loss, get a copy of our free booklet called The Memory Handbook.

What does memory loss look like in a person with dementia ?

Memory loss can be a symptom of any type of dementia. For people with Alzheimer’s disease , it is often among the very first signs.

Memory can be affected in different ways. These include:

• not being able to create new memories – this means that recent events are not ‘recorded’ in the person’s memory and so cannot be recalled later. For example, the person may forget a conversation they have just had.
• taking longer to retrieve information – this means that, even though the person is still able to recall things, this takes them much longer or they might need a prompt. For example, they might need more time to find the name for an object.
• not being able to retrieve information – this means that, even though the person may be able to create new memories, they are not able to access them when needed. For example, they may get lost in familiar surroundings or on journeys they have taken many times.

Memory loss affects everyone differently but many people with dementia experience some of the following:

• forgetting recent conversations or events (sometimes referred to as short-term memory loss)
• struggling to find the right word in a conversation
• forgetting names of people and objects
• losing or misplacing items (such as keys or glasses)
• getting lost in familiar surroundings or on familiar journeys
• forgetting how to carry out familiar tasks (such as making a cup of tea)
• forgetting appointments or anniversaries
• not being able to keep track of medication, and whether or when it has been taken
• struggling to recognise faces of people they know well.

These changes may be more visible to family and friends than to the person themselves.

For ideas on how to support someone with these memory problems, see ‘ Practical tips for supporting someone with memory loss ’.

Different types of memory problems

Older memories – which have been recalled or spoken about more often – are more firmly established than newer memories. This means that a person with dementia may forget recent events, but still be able to recall detailed memories from earlier life.

Dementia and the brain

Knowing more about the brain and how it can change can help to understand the symptoms of dementia. It can help a person with dementia to live well, or to support a person with dementia to live well.

In the same way, people with dementia may still be able to remember things that they have repeated many times in their life, such as a route to school. This also includes skills that involved a lot of practice, like playing a musical instrument or driving .

People with dementia may also be able to remember more emotional events such as weddings or birthday parties. This is because memory also has an emotional aspect to it. This emotional memory is usually affected much later on in dementia .

This means that a person with dementia may remember how they feel about an event even if they have forgotten the details of it. For example, they may not remember where they went on holiday, or that a friend came to visit, but they may still feel happy about it after.

This emotional memory can be triggered by senses, such as hearing a certain piece of music or smelling a certain fragrance. 

Listen to our helpsheet for a summary of the signs and symptoms of dementia.

Worried about memory problems?

If you or a loved one are experiencing memory loss, it could be a sign of something more serious. Our advice will help you understand your symptoms and get support.

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• Page last reviewed: 23 February 2021

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• Diseases & Conditions
• Mild cognitive impairment (MCI)

Mild cognitive impairment (MCI) is the stage between the expected decline in memory and thinking that happens with age and the more serious decline of dementia. MCI may include problems with memory, language or judgment.

People with MCI may be aware that their memory or mental function has "slipped." Family and close friends also may notice changes. But these changes aren't bad enough to impact daily life or affect usual activities.

MCI may increase the risk of dementia caused by Alzheimer's disease or other brain disorders. But some people with mild cognitive impairment might never get worse. And some eventually get better.

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The brain, like the rest of the body, changes with age. Many people notice they become more forgetful as they age. It may take longer to think of a word or to recall a person's name.

If concerns with mental function go beyond what's expected, the symptoms may be due to mild cognitive impairment (MCI). MCI may be the cause of changes in thinking if:

• You forget things more often.
• You miss appointments or social events.
• You lose your train of thought. Or you can't follow the plot of a book or movie.
• You have trouble following a conversation.
• You find it hard to make decisions, finish a task or follow instructions.
• You start to have trouble finding your way around places you know well.
• You begin to have poor judgment.
• Your family and friends notice any of these changes.

If you have MCI , you also may experience:

• Depression.
• A short temper and aggression.
• A lack of interest.

When to see a doctor

Talk to your health care provider if you or someone close to you notices you're having problems with memory or thinking. This may include trouble recalling recent events or having trouble thinking clearly.

• Changes in brain structure with MCI and Alzheimer's disease

Some changes in brain structure — such as the decrease in size of the brain's memory center (hippocampus) — are typical with aging. However, this reduction in size is greater in those with mild cognitive impairment and even more dramatic in people with Alzheimer's disease.

• Brain shrinkage in MCI and Alzheimer's disease

Dementia causes the brain to lose mass, especially in critical areas. Note the difference in size between a healthy brain (top), a mild cognitive impairment brain (middle) and an Alzheimer's disease brain (bottom).

There's no single cause of mild cognitive impairment (MCI), although MCI may be due to early Alzheimer's disease. There's no single outcome for the disorder. Symptoms of MCI may remain stable for years. Or MCI may progress to Alzheimer's disease dementia or another type of dementia. In some cases, MCI may improve over time.

MCI often involves the same types of brain changes seen in Alzheimer's disease or other forms of dementia. In MCI , those changes occur at a lesser degree. Some of these changes have been seen in autopsy studies of people with MCI .

These changes include:

• Clumps of beta-amyloid protein, called plaques, and tangles of tau proteins that are seen in Alzheimer's disease.
• Microscopic clumps of a protein called Lewy bodies. These clumps are associated with Parkinson's disease, dementia with Lewy bodies and some cases of Alzheimer's disease.
• Small strokes or reduced blood flow through brain blood vessels.

Brain-imaging studies show that the following changes may be associated with MCI :

• Decreased size of the hippocampus, a brain region important for memory.
• Increased size of the brain's fluid-filled spaces, known as ventricles.
• Reduced use of glucose in key brain regions. Glucose is the sugar that's the main source of energy for cells.

Risk factors

The strongest risk factors for MCI are:

• Increasing age.
• Having a form of a gene known as APOE e4 . This gene also is linked to Alzheimer's disease. But having the gene doesn't guarantee that you'll have a decline in thinking and memory.

Other medical conditions and lifestyle factors have been linked to an increased risk of changes in thinking, including:

• High blood pressure.
• High cholesterol.
• Obstructive sleep apnea.
• Lack of physical exercise.
• Low education level.
• Lack of mentally or socially stimulating activities.

Complications

People with MCI have an increased risk — but not a certainty — of developing dementia. Overall, about 1% to 3% of older adults develop dementia every year. Studies suggest that around 10% to 15% of people with MCI go on to develop dementia each year.

Mild cognitive impairment can't be prevented. But research has found some lifestyle factors may lower the risk of getting MCI . Studies show that these steps may help prevent MCI :

• Don't drink large amounts of alcohol.
• Limit exposure to air pollution.
• Reduce your risk of a head injury.
• Don't smoke.
• Manage health conditions such as diabetes, high blood pressure, obesity and depression.
• Practice good sleep hygiene and manage any sleep problems.
• Eat a healthy diet full of nutrients. Include fruits and vegetables and foods low in saturated fats.
• Stay social with friends and family.
• Exercise at a moderate to vigorous intensity most days of the week.
• Wear a hearing aid if you have hearing loss.
• Stimulate your mind with puzzles, games and memory training.

Mild cognitive impairment (MCI) care at Mayo Clinic

• Knopman DS, et al. Alzheimer disease. Nature Reviews. Disease Primers. 2021; doi:10.1038/s41572-021-00269-y.
• Jankovic J, et al., eds. Alzheimer disease and other dementias. In: Bradley and Daroff's Neurology in Clinical Practice. 8th ed. Elsevier; 2022. https://www.clinicalkey.com. Accessed Sept. 21, 2022.
• Zhuang L, et al. Cognitive assessment tools for mild cognitive impairment screening. Journal of Neurology. 2021; doi:10.1007/s00415-019-09506-7.
• What is mild cognitive impairment? National Institute on Aging. https://www.nia.nih.gov/health/what-mild-cognitive-impairment. Accessed Sept. 21, 2022.
• Mild cognitive impairment (MCI). Alzheimer's Association. https://www.alz.org/alzheimers-dementia/what-is-dementia/related_conditions/mild-cognitive-impairment. Accessed Sept. 21, 2022.
• Lewis JE, et al. The effects of twenty-one nutrients and phytonutrients on cognitive function: A narrative review. Journal of Clinical and Translational Research. 2021; doi:10.18053/jctres.07.202104.014.
• Kellerman RD, et al. Alzheimer's disease. In: Conn's Current Therapy 2022. Elsevier; 2022. https://www.clinicalkey.com. Accessed Sept. 21, 2022.
• Ferri FF. Mild cognitive impairment. In: Ferri's Clinical Advisor 2023. Elsevier; 2023. https://www.clinicalkey.com. Accessed Sept. 21, 2022.
• Petersen RC, et al. Practice guideline update summary: Mild cognitive impairment: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology. 2018; doi:10.1212/WNL.0000000000004826.
• Budson AE, et al. Subjective cognitive decline, mild cognitive impairment and dementia. In: Memory Loss, Alzheimer's Disease, and Dementia. 3rd ed. Elsevier; 2022. https://www.clinicalkey.com. Accessed Sept. 21, 2022.
• Cognitive impairment in older adults: Screening. U.S. Preventive Services Task Force recommendation statement. https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/cognitive-impairment-in-older-adults-screening. Accessed Sept. 21, 2022.
• Levenson JL, ed. Dementia. In: The American Psychiatric Association Publishing Textbook of Psychosomatic Medicine and Consultation-Liaison Psychiatry. 3rd ed. American Psychiatric Association Publishing; 2019. https://psychiatryonline.org. Accessed Sept. 21, 2022.
• Livingston G, et al. Dementia prevention, intervention, and care: 2020 report of the Lancet Commission. The Lancet. 2020; doi:10.1016/S0140-6736(20)30367-6.
• Cummings J, et al. Alzheimer's disease drug development pipeline: 2022. Alzheimer's and Dementia. 2022; doi:10.1002/trc2.12295.
• Memory, forgetfulness and aging: What's normal and what's not? National Institute on Aging. https://www.nia.nih.gov/health/memory-forgetfulness-and-aging-whats-normal-and-whats-not. Accessed Sept. 26, 2022.
• Ami T. Allscripts EPSi. Mayo Clinic. April 21, 2022.
• Alzheimer's disease research centers. National Institute on Aging. https://www.nia.nih.gov/health/alzheimers-disease-research-centers#minnesota. Accessed Sept. 26, 2022.
• About the Alzheimer's Consortium. Arizona Alzheimer's Consortium. https://azalz.org/about/#institutes. Accessed Sept. 26, 2022.
• Shi M, et al. Impact of anti-amyloid-β monoclonal antibodies on the pathology and clinical profile of Alzheimer's disease: A focus on aducanumab and lecanemab. Frontiers in Aging and Neuroscience. 2022; doi:10.3389/fnagi.2022.870517.
• Graff-Radford J (expert opinion). Mayo Clinic. Sept. 30, 2022.
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Memory loss and aging

Normal forgetfulness vs. dementia, symptoms of mild cognitive impairment (mci), when to see a doctor for memory loss, reversible causes of memory loss, compensating for memory loss, brain exercises to combat memory loss, age-related memory loss.

Worried about your forgetfulness? Learn what's normal when it comes to memory loss and aging, and how to recognize the signs of more serious problems.

We’ve all misplaced keys, blanked on someone’s name, or forgotten a phone number. When you’re young, you don’t tend to pay much attention to these lapses, but as you grow older, you may worry about what they mean. Perhaps you start to talk about a movie you saw recently when you realize you can’t remember the title. You’re giving directions to your house when you suddenly blank on a familiar street name. Or you find yourself standing in the middle of the kitchen wondering what you went in there for. Memory lapses can be frustrating, but most of the time they aren’t cause for concern. Age-related memory changes are not the same thing as dementia.

As you grow older, you experience physiological changes that can cause glitches in brain functions you’ve always taken for granted. It takes longer to learn and recall information. You’re not as quick as you used to be. In fact, you may mistake this slowing of your mental processes for true memory loss. But in most cases, if you give yourself time, the information will come to mind. So, while it’s true that certain brain changes are inevitable when it comes to aging, major memory problems are not one of them. That’s why it’s important to know the difference between normal age-related forgetfulness and the symptoms that may indicate a developing cognitive problem.

Age-related memory loss and the brain

The brain is capable of producing new brain cells at any age, so significant memory loss is not an inevitable result of aging. But just as it is with muscle strength, you have to use it or lose it. Your lifestyle, habits, and daily activities have a huge impact on the health of your brain. Whatever your age, there are many ways you can improve your cognitive skills , prevent memory loss, and protect your grey matter.

Furthermore, many mental abilities are largely unaffected by normal aging, such as:

• Your ability to do the things you’ve always done and continue to do often
• The wisdom and knowledge you’ve acquired from life experience
• Your innate common sense and your ability to form reasonable arguments and judgments

Three causes of age-related memory loss

• The hippocampus, a region of the brain involved in the formation and retrieval of memories, often deteriorates with age.
• Hormones and proteins that protect and repair brain cells and stimulate neural growth also decline with age.
• Older people often experience decreased blood flow to the brain , which can impair memory and lead to changes in cognitive skills.

For most people, occasional lapses in short-term memory are a normal part of the aging process, not a warning sign of serious mental deterioration or the onset of Alzheimer’s or another dementia.

The following types of memory lapses are normal among older adults and generally are not considered warning signs of dementia:

• Occasionally forgetting where you left things you use regularly, such as glasses or keys.
• Forgetting names of acquaintances or blocking one memory with a similar one, such as calling a grandson by your son’s name.
• Occasionally forgetting an appointment or walking into a room and forgetting why you entered.
• Becoming easily distracted or having trouble remembering what you’ve just read, or the details of a conversation.
• Not quite being able to retrieve information you have “on the tip of your tongue.”

Does your memory loss affect your ability to function?

The primary difference between age-related memory loss and dementia is that the former isn’t disabling. The memory lapses have little impact on your daily performance and ability to do what you want to do. Dementia, on the other hand, is marked by a persistent, disabling decline in two or more intellectual abilities such as memory, language, judgment, and abstract thinking.

When memory loss becomes so pervasive and severe that it disrupts your work, hobbies, social activities, and family relationships, you may be experiencing the warning signs of Alzheimer’s disease , or another disorder that causes dementia, or a condition that mimics dementia.

Mild cognitive impairment (MCI) is an intermediate stage between normal age-related cognitive changes and the more serious symptoms that indicate dementia.

MCI can involve problems with memory, language, thinking, and judgment that are greater than normal age-related changes, but the line between MCI and normal memory problems is not always a clear one. The difference is often one of degrees. For example, it’s normal as you age to have some problems remembering the names of people. However, it’s not normal to forget the names of your close family and friends and then still be unable to recall them after a period of time.

If you have mild cognitive impairment, you and your family or close friends will likely be aware of the decline in your memory or mental function. But, unlike people with full-blown dementia, you are still able to function in your daily life without relying on others.

[Read: Mild Cognitive Impairment (MCI)]

While many people with MCI eventually develop Alzheimer’s disease or another type of dementia, that doesn’t mean it’s inevitable. Some people with MCI plateau at a relatively mild stage of decline while others even return to normal. The course is difficult to predict, but in general, the greater the degree of memory impairment, the greater your risk of developing dementia some time in the future.

Symptoms of MCI 

Common symptoms include:

• Frequently losing or misplacing things.
• Frequently forgetting conversations, appointments, or events.
• Difficulty remembering the names of new acquaintances.
• Difficulty following the flow of a conversation.

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It’s time to consult a doctor when memory lapses become frequent enough or sufficiently noticeable to concern you or a family member. If you get to that point, make an appointment as soon as possible to talk with your primary physician and have a thorough physical examination. Even if you’re not displaying all the necessary symptoms to indicate dementia, now may be a good time to take steps to prevent a small problem becoming a larger one.

Your doctor can assess your personal risk factors, evaluate your symptoms, eliminate reversible causes of memory loss, and help you obtain appropriate care. Early diagnosis can treat reversible causes of memory loss, lessen decline in vascular dementia , or improve the quality of life in Alzheimer’s or other types of dementia.

What to expect at your doctor’s visit

The doctor will ask you a lot of questions about your memory, including:

• How long have you or others noticed a problem with your memory?
• What kinds of things have been difficult to remember?
• Did the difficulty come on gradually or suddenly?
• Are you having trouble doing ordinary things?

The doctor also will want to know what medications you’re taking, how you’ve been eating and sleeping, whether you’ve been depressed or stressed lately, and other questions about what’s been happening in your life. Chances are the doctor will also ask you or your partner to keep track of your symptoms and check back in a few months. If your memory problem needs more evaluation, your doctor may send you to a neuropsychologist.

It’s important to remember that memory loss doesn’t automatically mean that you have dementia. There are many other reasons why you may be experiencing cognitive problems, including stress, depression, and even vitamin deficiencies. That’s why it’s so important to go to a doctor to get an official diagnosis if you’re experiencing problems.

[Read: What’s Causing Your Memory Loss?]

Sometimes, even what looks like significant memory loss can be caused by treatable conditions and reversible external factors, such as:

Depression. Depression can mimic the signs of memory loss, making it hard for you to concentrate, stay organized, remember things, and get stuff done. Depression is a common problem in older adults —especially if you’re less social and active than you used to be or you’ve recently experienced a number of important losses or major life changes (retirement, a serious medical diagnosis, the loss of a loved one, moving out of your home).

Vitamin B12 deficiency. Vitamin B12 protects neurons and is vital to healthy brain functioning. In fact, a lack of B12 can cause permanent damage to the brain. Older people have a slower nutritional absorption rate, which can make it difficult for you to get the B12 your mind and body need. If you smoke or drink, you may be at particular risk. If you address a vitamin B12 deficiency early, you can reverse the associated memory problems. Treatment is available in the form of a monthly injection.

Thyroid problems. The thyroid gland controls metabolism: if your metabolism is too fast, you may feel confused, and if it’s too slow, you can feel sluggish and depressed. Thyroid problems can cause memory problems such as forgetfulness and difficulty concentrating. Medication can reverse the symptoms.

Alcohol abuse. Excessive alcohol intake is toxic to brain cells, and alcohol abuse leads to memory loss. Over time, alcohol abuse may also increase the risk of dementia. Because of the damaging effects of excessive drinking, experts advise limiting your daily intake to just 1-2 drinks.

Dehydration. Older adults are particularly susceptible to dehydration. Severe dehydration can cause confusion, drowsiness, memory loss, and other symptoms that look like dementia. It’s important to stay hydrated (aim for 6-8 drinks per day). Be particularly vigilant if you take diuretics or laxatives or suffer from diabetes, high blood sugar, or diarrhea.

Side effects of medication. Many prescribed and over-the-counter drugs or combinations of drugs can cause cognitive problems and memory loss as a side effect. This is especially common in older adults because they break down and absorb medication more slowly. Common medications that affect memory and brain function include sleeping pills, antihistamines, blood pressure and arthritis medication, muscle relaxants, anticholinergic drugs for urinary incontinence and gastrointestinal discomfort, antidepressants, anti-anxiety meds, and painkillers.

Are you taking three or more drugs?

As well as certain individual medications, taking too many medications can also create cognitive problems. A recent study found that the more medications you take, the higher your risk for brain atrophy. Researchers found that the loss of gray matter was most acute in people who took three or more different medications. If you are concerned about the medications you’re taking, talk to your doctor. But do NOT stop taking your medications without your doctor’s consent.

The same practices that contribute to healthy aging and physical vitality also contribute to a healthy memory. So, by taking steps early to prevent cognitive decline, you’ll also be improving all other aspects of your life as well.

[Read: Preventing Alzheimer’s Disease]

Stay social. People who aren’t socially engaged with family and friends are at higher risk for memory problems than people who have strong social ties. Quality face-to-face social interaction can greatly reduce stress and is powerful medicine for the brain, so schedule time with friends, join a book club, or visit the local senior center. And be sure to put your phone away and focus fully on the people you’re with if you want the full brain benefit.

Stop smoking. Smoking heightens the risk of vascular disorders that can cause stroke and constrict arteries that deliver oxygen to the brain. When you quit smoking , the brain quickly benefits from improved circulation.

Manage stress. Cortisol, the stress hormone, damages the brain over time and can lead to memory problems. But even before that happens, stress or anxiety can cause memory difficulties in the moment. When you’re stressed out or anxious, you’re more likely to suffer memory lapses and have trouble learning or concentrating. But simple stress management techniques can minimize these harmful effects.

Get enough sleep. Getting a good night’s sleep as you age is necessary for memory consolidation, the process of forming and storing new memories so you can retrieve them later. Sleep deprivation reduces the growth of new neurons in the hippocampus and causes problems with memory, concentration, and decision-making. It can even lead to depression—another memory killer.

Watch what you eat. Eat plenty of fruits and vegetables and drink green tea as these foods contain antioxidants in abundance, which can keep your brain cells from “rusting.” Foods rich in omega-3 fats (such as salmon, tuna, trout, walnuts, and flaxseed) are particularly good for your brain and memory. Eating too many calories, though, can increase your risk of developing memory loss or cognitive impairment.

Exercise regularly. Starting a regular exercise routine , including cardio and strength training, may reduce your risk of developing dementia by up to 50 percent. What’s more, exercise can also slow further deterioration in those who have already started to develop cognitive problems. Exercise protects against Alzheimer’s by stimulating the brain’s ability to maintain old connections as well as make new ones.

Walking: An easy way to fight memory loss

New research indicates that walking six to nine miles every week can prevent brain shrinkage and memory loss. According to the American Academy of Neurology, older adults who walked between six and nine miles per week had more gray matter in their brains nine years after the start of the study than people who didn’t walk as much.

Just as physical exercise can make and keep your body stronger, mental exercise can make your brain work better and lower your risk of mental decline. Try to find brain exercises that you find enjoyable. The more pleasurable an activity is to you, the more powerful its effect will be on your brain. You can make some activities more enjoyable by appealing to your senses—by playing music during the exercise, for example, or lighting a scented candle, or rewarding yourself after you’ve finished.

[Read: How to Improve Your Memory]

Here are some ideas for brain exercise, from light workouts to heavy lifting:

• Play games you are not already familiar with that involve strategy, like chess or bridge, and word games like Scrabble. Try crossword and other word puzzles, or number puzzles such as Sudoku.
• Read newspapers, magazines, and books that challenge you.
• Get in the habit of learning new things: games, recipes, driving routes, a musical instrument, a foreign language. Take a course in an unfamiliar subject that interests you. The more interested and engaged your brain, the more likely you’ll be to continue learning and the greater the benefits you’ll experience.
• Improve how well you do existing activities. If you already speak a foreign language, commit to improving your fluency. Or if you’re a keen golfer, aim to lower your handicap.
• Take on a project that involves design and planning, such as a new garden, a quilt, or a koi pond.

More Information

• Neurocognitive Disorders. (2013). In Diagnostic and Statistical Manual of Mental Disorders . American Psychiatric Association. Link
• American Psychiatric Association. (2013). Neurocognitive Disorders. In Diagnostic and Statistical Manual of Mental Disorders . American Psychiatric Association. Link
• National Institute on Aging. (2018). Understanding Memory Loss . National Institutes of Health. Link
• Livingston, G., Huntley, J., Sommerlad, A., Ames, D., Ballard, C., Banerjee, S., Brayne, C., Burns, A., Cohen-Mansfield, J., Cooper, C., Costafreda, S. G., Dias, A., Fox, N., Gitlin, L. N., Howard, R., Kales, H. C., Kivimäki, M., Larson, E. B., Ogunniyi, A., … Mukadam, N. (2020). Dementia prevention, intervention, and care: 2020 report of the Lancet Commission. The Lancet, 396(10248), 413–446. Link
• National Academies of Sciences, E. (2020). Social Isolation and Loneliness in Older Adults: Opportunities for the Health Care System. Link
• Morris, M. C., Tangney, C. C., Wang, Y., Sacks, F. M., Barnes, L. L., Bennett, D. A., & Aggarwal, N. T. (2015). MIND diet slows cognitive decline with aging. Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, 11(9), 1015–1022. Link
• McEvoy, C. T., Guyer, H., Langa, K. M., & Yaffe, K. (2017). Neuroprotective diets are associated with better cognitive function: The Health and Retirement Study. Journal of the American Geriatrics Society, 65(8), 1857–1862. Link

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Diagnosis and Management of Dementia: A Review

Zoe arvanitakis.

1 Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago, IL.

2 Dept of Neurological Sciences, Rush University Medical Center, Chicago, IL.

Raj C. Shah

3 Dept of Family Medicine, Rush University Medical Center, Chicago, IL.

David A. Bennett

Collection, management, analysis, and interpretation of the data: Dr. Arvanitakis.

Preparation, review, or approval of the manuscript: Drs. Arvanitakis, Shah, and Bennett.

Decision to submit the manuscript for publication: Drs. Arvanitakis and Bennett.

Associated Data

Worldwide, 47 million people live with dementia and, by 2050, the number is expected to increase to 131 million.

Observations

Dementia is an acquired loss of cognition in multiple cognitive domains sufficiently severe to affect social or occupational function. In the US, Alzheimer’s disease (AD) affects 5.8 million people. However, dementia is commonly associated with more than one neuropathology, usually AD with cerebrovascular pathology. Diagnosing dementia requires a history evaluating for cognitive decline and impairment in daily activities, with corroboration from a close friend or family member, in addition to a moderately extended mental status examination by a clinician to delineate impairments in memory, language, attention, visuospatial cognition such as spatial orientation, executive function, and mood. Brief cognitive impairment screening questionnaires can assist in initiating and organizing the cognitive assessment. However, if the assessment is inconclusive (e.g., symptoms present, but normal examination), neuropsychological testing can help with a diagnosis. Physical examination may help identify the etiology of dementia. For example, focal neurologic abnormalities suggest stroke. Brain neuroimaging may demonstrate structural changes including, but not limited to, focal atrophy, infarcts, and tumor, that may not be identified on physical examination. Additional evaluation with cerebrospinal fluid assays or genetic testing should be considered in atypical dementia cases, such as age of onset under 65 years, rapid symptom onset, and/or impairment in multiple cognitive domains but not episodic memory. For treatment, patients benefit from non-pharmacologic approaches, including cognitively engaging activities such as reading, physical exercise such as walking, and socialization such as family gatherings. Pharmacologic approaches can provide modest symptomatic relief. For AD, this includes an acetylcholinesterase inhibitor such as donepezil for mild-to-severe dementia, and memantine (used alone or as an add-on therapy) for moderate-to-severe dementia. Rivastigmine is approved for the symptomatic treatment of Parkinson’s disease dementia.

Conclusions and Relevance

AD currently affects 5.8 million persons in the US, and is a common cause of dementia which is usually accompanied by other neuropathology. Causes of dementia can be diagnosed by medical history, cognitive and physical examination, laboratory testing, and brain imaging. Management should include both non-pharmacologic and pharmacologic approaches.

INTRODUCTION

Dementia is a common public health problem. 1 Worldwide, approximately 47 million people have dementia and this number is expected to increase to 131 million by 2050. 1 Reductions in age-adjusted incidence of dementia have occurred in the United States (US) and other developed countries over the last 20 years, perhaps associated with increasing formal educational attainment. However, without improved treatments or preventive therapy, the adverse consequences of dementia will continue to increase. 2

In the US, the prevalence of dementia is 15% in people older than 68 years. 3 Dementia is most commonly attributed to Alzheimer’s disease (AD), with over five million people currently affected by AD, and 13.8 million are projected to be affected by the year 2050. 4 AD is the 6 th leading cause of death, and the 5 th leading cause among persons older than 65 years. 5 , 6 This review summarizes diagnosis and management of dementia, defined as significant cognitive impairment in two or more cognitive domains.

We conducted a literature search in PubMed, using the search terms “dementia and (diagnosis or management)” in the title field. The following inclusion criteria were applied: a publication date from November 19, 2013 to June 29, 2019; English language; female or male sex; and “aged, 65 + years” (to exclude studies about less common causes of dementia). Original research studies with sample sizes less than 100 persons were excluded.

OBSERVATIONS

The search yielded 200 articles published in the past five and a half years. We excluded 37 studies with fewer than 100 persons, 52 on topics not relevant to this review, 41 about non-US public policy or practice, 20 about caregivers, 7 about pathology, 5 about medical record documentation or coding, and 11 that were not original research. The remaining 27 articles of original research, including 22 observational studies and 5 randomized clinical trials, informed this review.

Risk factors and Neuropathology

Aging is an important risk factor for all-cause dementia. AD affects 5–10% of people older than 65 years, and 50% of those 85 years old. 7 Non-modifiable risk factors for AD include female sex, Black race, Hispanic ethnicity, and genetic factors such as the apolipoprotein E ( APOE) gene. 8 – 13 Modifiable risk factors for all-cause dementia include hypertension and diabetes, diet, and limited cognitive, physical, and social activities. 14 – 18 Pathologically, “mixed dementia” is the most common form of dementia, found in 46% of persons with clinically diagnosed AD, and most commonly consisting of AD neurodegeneration and cerebrovascular disease. 19 Other neurodegenerative pathologies such as Lewy body disease (pathologically confirmed in 17% of cases) and frontotemporal lobar degeneration (in <5% of cases) are less frequent. 19 – 25

Definition and Characterization

Dementia is defined by chronic, acquired loss of two or more cognitive abilities caused by brain disease or injury ( Box 1 ). This definition has been used in clinical practice for decades, although recent changes in the Diagnostic Statistical Manual, 5 th Edition, have moved away from using the term dementia and have recognized that dementia can be present with impairment in a single domain (i.e. by this definition, a patient with a severe expressive aphasia could be classified as having dementia). 26 , 27 Memory requires the recording, storage, and retrieval of information. The most common clinical presentation of AD is a slow onset and gradually progressive loss of memory, typically with inability to learn new information and particularly autobiographical information, such as recent events in ones’ life. This is because AD preferentially affects brain networks involved in episodic memory. Examples of episodic memory loss include forgetting appointments, to pay bills or to take medication. Typically, a person with AD repeats questions and conversations. The memory loss is often accompanied by subjective memory complaints. Difficulty recalling names which are recalled later, is common in aging but is not a typical early sign of dementia. Mild cognitive impairment (MCI) is defined by performance that is lower than normal on objective neuropsychological testing of cognition, but with maintained daily functions (e.g., maintained abilities to function within society such as for daily activities at work, home, and in social settings, and maintained activities of daily living such as for personal care) and therefore not consistent with dementia ( Box 1 ). 28 MCI can be categorized into “amnestic” MCI, in which reduced performance on memory is the key finding, versus “non-amnestic” MCI, in which reduced cognitive performance is in a non-memory domain such as language. MCI can also be characterized into “single domain” versus “multi-domain” MCI, in which multiple cognitive performance measures are impaired. MCI does not always progress to dementia, and a patient’s cognitive status may become normal or fluctuate between MCI, normal cognition, and dementia. Fluctuations in cognition are also present in some conditions including neurodegenerative diseases (such as in early stages of Lewy body disease), cerebrovascular disease (e.g., intermittent small strokes), and psychiatric conditions (e.g., depression, anxiety), and with medications affecting cognition (e.g., opioids), and variability in cognitive test results.

Dementia is a clinical syndrome with variable manifestations ( Table 1 ), which help attribute the cause of dementia and guide management. While research studies have defined a “preclinical” AD, 27 , 29 in clinical care, AD is not diagnosed before symptom onset. Differentiating AD from other causes of dementia is easiest in the early stage of illness, as dementias in the late stage look similar ( Table 2 ). 30 – 34

Manifestations of dementia *

Clinical and pathologic characteristics differentiating select causes of dementia

Because mixed dementia is common, the evaluation focuses on identifying conditions likely to contribute to dementia ( Box 1 and Table 2 ). Cerebrovascular disease is the most frequent co-morbid condition with AD, and evidence of cerebrovascular disease does not reduce the likelihood of AD. However, approximately five percent of people with dementia show evidence of only cerebrovascular disease. After AD, the most common neurodegenerative dementias are Lewy body disease, characterized by chronic REM behavior disorder with early visuospatial impairment and parkinsonism, 21 , 22 , 32 , 33 and frontotemporal dementia, characterized by a behavioral variant (the most common presentation is disinhibition) or less often, a language impairment variant (such as a semantic dementia, in which the meaning of the patient’s speech is unclear; Table 2 ). 23 , 34

Diagnosis and Management

Clinical evaluations, differential diagnosis, and management of dementia most commonly occur in the primary care setting, with appropriate specialist input as needed.

Clinical Evaluation for Diagnosis

The 2014 US Preventive Services Task Force indicated that there was insufficient evidence to evaluate the balance of benefits and harms for universal screening for cognitive impairment using formal screening instruments in community-dwelling adults age 65 years and older. 35 While the Task Force concluded that adequate evidence existed for some screening tools that have sufficiently high sensitivity and specificity for identifying dementia, there is no published evidence of the effect of screening on decision making or planning by patients, clinicians, or caregivers. 35 However, report of memory complaints 36 – 38 or rapidly-progressive cognitive problems over several months may indicate an underlying medical condition that warrants further evaluation with cognitive, laboratory, and other tests. 39 – 40

Evaluation of possible dementia requires a brief medical history and a cognitive and neurologic examination ( Box 2 ). The history remains the most important diagnostic tool and should be obtained from both the patient and a close family member or friend. While some patients complain of forgetfulness, others are unable to recall details of their history and in some instances have anosognosia (i.e., lack of insight into one’s disease). One clue that a patient has a memory problem occurs when the person accompanying them provides the medical history. The history should characterize the nature, magnitude, and course of cognitive changes. The nature refers to the cognitive domains affected. Is there loss of episodic memory (e.g., what the patient did that morning, yesterday, and last week), or language abilities (e.g., word finding difficulties with circumlocutions)? The magnitude refers to the severity: does the cognitive loss affect daily functions, such as the patient’s ability to manage her own affairs (e.g., does she get lost while driving, not pay her bills, forget to take medications)? Is the course with an insidious onset and a slow progression (as in neurodegeneration) or a rapid onset and fluctuating and stepwise progression (as in cerebrovascular disease)? The history should focus on medical conditions that could affect cognition including vascular disease risk factors (such as hypertension and diabetes), existing brain conditions (such as stroke, Parkinson’s Disease, head trauma), and use of medications that can impair cognition (e.g., sleep aids and anxiolytics such as benzodiazepines; analgesics such as codeine containing agents; anticholinergics such as tricyclic antidepressants and bladder antimuscarinics). 41 , 42 A family history might identify young-onset dementia (onset in persons younger than 65 years) in first-degree relatives, suggesting one of the rare inherited genetic forms of dementia.

The cognitive examination identifies the presence, severity, and nature of cognitive impairment (e.g., memory versus language), and should consider cultural, linguistic, educational, and other factors such as anxiety and sleep deprivation. One commonly used screening tool is the Montreal Cognitive Assessment (MoCA; range 0–30, follow-up evaluation to screening recommended if score <24/30). The MoCA requires about 10 minutes to administer and is useful in early detection of cognitive impairment, including MCI with executive dysfunction. 43 The Mini-Mental State Exam was developed more than 4 decades ago. It is less sensitive to the presence of MCI and less thoroughly evaluates the domains of executive function, higher-level language skills, and complex visuospatial processing. 43 – 47

The neurologic examination evaluates for objective evidence of neurocognitive problems such as aphasia, apraxia, and agnosia. Unusual behaviors, such as disinhibition with hyperorality or hypersexuality, suggest a frontotemporal dementia, which comprises a group of uncommon conditions associated with neuronal loss beginning in the frontal and/or temporal regions of the brain while other areas are relatively spared. The examination may demonstrate focal neurologic signs or parkinsonism (e.g., as typically seen in the early stages of Lewy body disease). The routine evaluation also includes physical examination to identify systemic vascular disease and systemic signs which may be pertinent to rarer causes of dementia (e.g., golden-brown eye discoloration [Kayser-Fleischer rings] of Wilson’s disease).

The routine work-up typically includes a limited number of blood tests (e.g., B12 and TSH) and neuroimaging to identify cortical and hippocampal atrophy (as seen in AD), or neuropathology including potentially treatable causes of dementia (e.g., resectable tumor, or normal pressure hydrocephalus which may be shunted), using brain imaging with either MRI or CT ( Box 2 ). 48 – 53 Additional evaluation is sometimes warranted. For example, in highly-educated and highly-functioning individuals, a compelling history of cognitive decline (e.g., no longer able to perform a complex task which could easily be done a year ago, such as filling a tax return or working at a cognitively demanding job such as doctor or lawyer), can suggest dementia despite the presence of “normal” function on a brief, screening cognitive test. In this instance, referral for detailed neuropsychological testing should be considered to assess a broader range of cognitive abilities (e.g., memory, executive function, language, attention, visuospatial abilities) with increased levels of difficulty. 54

If the etiology of dementia is unclear after a brief history and examination, additional history and examination, and select blood, neurologic and medical tests should be considered ( Box 2 ).

Recent biomedical advances have led to additional tests that may be helpful in the differential diagnosis of dementia, in particular disease biomarkers which are still commonly used in research. 55 For a patient whose presentation is not consistent with AD (commonly called “atypical dementia”; see Supplemental Materials , eTable 1 ) and for patients in whom diagnostic certainty is low, clinicians may consider specialist referral and additional testing. Functional neuroimaging 56 such as positron emission tomography (PET) 57 can show changes suggestive of AD, usually asymmetric, bilateral temporal-parietal hypometabolism with routine tracers such as fluorodeoxyglucose (FDG) which has a sensitivity of 91% and a specificity of 85% for AD. 58 – 59 FDG PET, covered by health insurance for suspected frontotemporal dementia, may differentiate this etiology from AD, facilitating diagnosis of this less common cause of dementia. For patients with frontotemporal dementia, FDG PET typically shows decreased, asymmetric frontal lobe hypometabolism in the behavioral variant, and anterior temporal lobe hypometabolism in the language (semantic) variant. 60 Amyloid PET can also be used in patients with cognitive impairment who are evaluated for AD or other causes of cognitive decline. 58 – 59 , 61 In a recent observational, multisite, longitudinal study of Medicare beneficiaries, amyloid PET results were associated with change in management plans in more than 60% of patients, compared to pre-PET scan. Change in management plans consisted of change in AD medication or other medication therapy, and changes in counseling about safety and future planning. 62 However, there is no evidence that PET scan changes clinical outcomes. Functional neuroimaging with tau radioligands are only appropriate for research purposes. 63

Cerebrospinal fluid (CSF) testing may be considered to obtain evidence of AD (low amyloid and high tau levels), other neurodegenerative disease (e.g., elevated protein 14–3-3 for Creutzfeldt-Jakob disease) or other etiologies (e.g., positive cultures in infection, oligoclonal bands in demyelination; improved gait after high volume CSF removal in normal pressure hydrocephalus). 64 – 68 Genetic testing may be reasonable, usually for young patients with a history of first-degree relatives with young-onset dementia (e.g., parents or siblings with dementia in their fourth or fifth decade of life). Rare autosomal dominant forms of dementia (e.g., presenilin gene mutations) warrant genetic counseling to determine whether other family members need to be screened. 69 Assessment for the APOE genotype is not recommended for routine evaluation of AD because most people with AD dementia do not have either the protective ε2 allele or the ε4 allele (associated with increased risk) and, more importantly, because currently, medical management would not be altered by the test results. 8 Additional neurologic work-up, such as for amyotrophic lateral sclerosis and medical work-up, such as for cardiac, metabolic, and other etiologies, may be considered with particular attention to ruling out reversible causes of cognitive impairment such as psychiatric disorders (depression) and thyroid dysfunction (see Supplemental Materials , eTable 2 ). 70

The overall goals are to reduce suffering caused by the cognitive and accompanying symptoms (e.g., in mood and behavior), while delaying progressive cognitive decline. Both non-pharmacologic and pharmacologic approaches are used to achieve the overall goals.

Non-pharmacologic management

For complex manifestations of dementia, referrals to specialists, such as clinician managers (e.g., geriatric nurse practitioners), social workers, occupational or speech therapists, and others may be helpful. Evidence primarily from observational studies and a few randomized controlled trials suggest potential benefits of select non-pharmacologic approaches in dementia ( Box 3 ). Although data demonstrating benefit are limited, they are inexpensive and generally safe. Cognitive training and activities such as reading and playing cognitively engaging games (e.g., chess, bridge) may help maintain cognition and function, as shown in randomized trials. 71 – 73 However, frustration and stress from challenging tasks should be avoided. Music or art therapy, and other experiential approaches, may help maintain cognition or improve quality of life. 74 Because old memories of childhood are preserved the longest, reminiscence therapy, consisting of psychotherapy using the personal history of an individuals’ early-life stories and events, may improve psychological well-being. 75

Physical exercise, both aerobic (e.g., walking, swimming) and non-aerobic/conditioning (e.g., weights), improves cardiovascular health through benefits on blood pressure and stroke risk, and randomized trials suggest these interventions may positively affect cognitive and physical function. 76 – 78 But, not all randomized trials have shown benefits from exercise for cognition. 79 – 80 In a randomized clinical trial, a comprehensive sleep education training program reduced night-time awakenings, total time awake at night, and depressive symptoms over 6 months. 81 Social activities may be beneficial, including participating in birthday parties, holidays, support groups with cognitively impaired individuals, and interacting with trained pets (e.g., dog therapy). Eating a brain-healthy diet (e.g., nuts, berries, leafy greens, fish) or a Mediterranean diet is also suggested. 82 – 85 A randomized clinical trial found that a combined diet, exercise, cognitive training, and vascular risk monitoring intervention improved cognition in people at-risk for cognitive decline. 86 However, patients with moderate-to-severe dementia have difficulty participating in cognitive, physical, and social activities, and activities should be limited when patients can no longer participate safely and productively.

Day care centers and assisted living facilities may also be helpful for either the patient or caregiver, but may not delay nursing home admission. 87 A randomized trial of staff and persons in residential care facilities showed that a clinical protocol for behavioral and psychological symptoms of dementia used by staff, improved patients’ behavioral symptoms and staff stress. 86 In the terminal phase of dementia, palliative care may be helpful.

Clinical attention for the caregiver, often a close relative, is important. While efforts continue to effectively deliver primary care for dementia, 88 caregiver education and interventions may improve outcomes for patients with dementia, and inexpensive and useful information is available (See Supplemental Materials , eTable 3 ). Safety, including for the patient’s mental, physical, and financial well-being, should be monitored by the caregiver, with attention to home safety, such as risk of kitchen fires which may be associated with patient burns. 89 Other home safety measures include controlling medication intake, limiting access to firearms and other weapons, and monitoring for elder abuse. Safety outside the home includes at work, where the caregiver may facilitate the patient cutting back or stopping work, for instance if managing machinery or making decisions regarding a company’s finances. Also, driving may need to be modified, including limiting driving to neighborhood and daytime driving to prevent getting lost. While no single test is associated with better driving safety, driving ability should be re-assessed periodically and cessation recommended based on dementia severity, to prevent accidents and injuries. 90 The caregiver can assist in planning for health care and finances as soon as possible in the course of the illness, to determine advanced directives before late-stage dementia. 91 Educating the family on effective communication with a person with dementia, who eventually develop aphasia, is important. Similarly, family should be educated on promoting psychological health and socially adaptive behaviors (e.g., simple and clear instructions to encourage cooperation with activities to address physical and mental health needs, without inciting agitation or aggression).

Behavioral problems, such as physical aggression, are a main cause of emergency room visits and institutionalization, and are associated with poor outcomes for patients (e.g., psychological and medical complications) and families. 92 , 93 Caregiver interventions may prevent patient institutionalization. For example, the family can learn to recognize fear, frustration, and anger (e.g., yelling, lashing out), and address signs of aggression (e.g., by redirecting the patients’ attention to something they enjoy), potentially preventing negative outcomes. 94

An important consideration for families with a member who has dementia, is the high burden of caregiving. 95 This burden may be physical/medical (e.g., neglect of caregiver’s own health, with potential medical complications), emotional and psychological (stress, burnout, depression), and/or financial. Prevention, early recognition, and treatment of these issues (e.g., referrals to social work for additional support), are integral to an effective management plan. A randomized trial demonstrated that delivering caregiver assistance in-person versus by telephone only, both improved care quality and without differences in effectiveness. 96

Pharmacologic management

Table 3 shows the Food and Drug Administration (FDA) approved drugs for AD dementia. Five drugs, four of which are currently available for prescription, yield modest symptomatic benefit for cognitive symptoms. Acetylcholinesterase inhibitors were the first drugs approved in the US for AD. These drugs inhibit the brain acetylcholinesterase enzyme, thereby promoting relative increases in acetylcholine abundance at the synaptic cleft for cholinergic neurotransmission. In a meta-analysis review of 10 randomized, double blind, placebo controlled trials each with a six month duration of drug exposure, acetylcholinesterase inhibitors were associated with 2.4 points slower decline (95%CI −2.7 to −2.0; p<0.00001) in a research measure of cognition spanning 70 points. 97 This is equivalent to about 6 months of decline from natural history studies of AD dementia, but the magnitude of the clinically relevant benefit is uncertain. 35 Also, modest improvements were observed in activities of daily living and behaviors. The efficacy of anticholinesterase inhibitors is similar among the individual drugs (donepezil, rivastigmine, galantamine). 96 Given the modest benefits and known risks, clinicians should engage in shared decision making regarding the initiation of an acetylcholinesterase inhibitor for the symptomatic treatment of AD dementia. 90

Approved * pharmacologic treatments for dementia attributed to AD

Each drug shown in Table 3 is available for use orally, and one is also available for transdermal use (rivastigmine). A slow titration dosing regimen over 4–8 weeks is recommended to reach the target dose and minimize adverse effects for all of the drugs. Some drugs are used at different maintenance doses depending on effects/adverse effects. For example, donepezil maintenance can be at 5 mg (e.g., if higher dose is associated with poor tolerability), 10mg (typical target), or 23 mg (rarely used), once daily. Despite a slow titration, adverse effects, such as gastrointestinal (e.g., nausea, vomiting, and diarrhea; in about 5 percent of users) may occur ( Table 3 ). Adverse effects may be higher than previously recognized. 98 If encountered, dosage may be lowered (e.g., from 10 mg of donepezil to 5 mg), either temporarily (e.g., days to weeks) before re-escalating more slowly and monitoring for recurrence of adverse effects (family instructed to call clinician if adverse effects). Alternatively, the drug can be discontinued and a different drug can be prescribed even in the same class (another acetylcholinesterase inhibitor), given that adverse effects vary among same-class drugs. 99 Approximately 5 percent of patients discontinue the drug due to adverse effects. If tolerated, annual brief assessments using the history (e.g., progression of cognitive problems, new cognitive problems, functional status) and a brief cognitive test can be used in the absence of new problems. Often, clinicians cannot appreciate a benefit and must rely on caregiver reports. A good response to a drug would result in the caregiver noticing a slight improvement in day-to-day life (e.g., improved ability to function at home). Routine cognitive tests such as the MoCA, 43 can be used to monitor disease course on treatment, and to identify unexpected trends such as rapid decline which would prompt consideration for a medical evaluation (e.g., for systemic infection). However, benefits are typically not seen on such routine tests. Monitoring requires periodic re-evaluation of cognition, function, neuropsychiatric and behavioral symptoms, and medication reconciliation. 100 – 103

As neurodegeneration in AD progresses, further cognitive and functional decline invariably occur, and consideration should be given in the moderate-to-severe stages of dementia for adding memantine ( Table 3 ). Memantine can also be used as a first-line drug, for instance when a patient with moderate dementia presents for a first evaluation but is not taking any medication for cognition. Another use is for patients who cannot tolerate an acetylcholinesterase inhibitor. Adverse effects of memantine include headaches and constipation.

Aside from AD, few other dementia etiologies have approved pharmacologic treatments for cognitive symptoms, and no disease specific treatments exist for Lewy body disease or frontotemporal dementia. In addition to AD, rivastigmine has also received approval for Parkinson disease dementia. There are currently no FDA-approved drugs for MCI, 104 and studies of acetylcholinesterase inhibitors failed to show benefit in this population. 105 At this time, more than 100 drugs are being investigated for dementia and cognition, and include potential disease modifying agents. 106 – 107

Medical management should address common causes of cognitive impairment and dementia, including polypharmacy which affects a third of persons older than 60 years. 108 – 109 Special considerations may be appropriate for patients with medical comorbidities (e.g., kidney dysfunction). Another approach in dementia management is reducing brain ischemia and stroke risk by treating vascular risk factors (hypertension, diabetes, hyperlipidemia) and consideration of the risk-benefit ratio for anti-thrombotics and anticoagulants (if prior stroke or atrial fibrillation are present). A recent randomized clinical trial of dementia prevention showed that intensive blood pressure lowering in persons with hypertension (comparing a target systolic blood pressure below 120mmHg, to a pressure between 120–140mmHg) did not reduce risk of dementia, but did reduce the combined rate of MCI or probable dementia in a post-hoc analysis. 110

Dementia is often accompanied by neuropsychiatric and behavioral problems. About 95% of patients have at least mild symptoms, most commonly apathy (83%) and depression (63%). 111 Approved treatments do not exist for these non-cognitive manifestations in the setting of dementia. For depression, a low dose antidepressant can be tried such as with a selective serotonin-reuptake inhibitor (e.g., escitalopram). Management of agitation and aggression can be challenging. Conventional antipsychotics such as haloperidol, should be avoided. 112 Newer generation “atypical” antipsychotics such as risperidone and quetiapine fumarate, should be avoided if possible, given their association with serious risks, especially in older patients. 113 Specifically, death, cardiac effects such as heart failure, and stroke, have resulted in a black box warning. Therefore, antipsychotics should only be used in controlled environments (e.g., under close medical supervision) and for a limited time only (e.g., a few weeks) when all other non-pharmacologic approaches have failed or the patient’s behavior poses a substantial threat to themselves or others. 112

CONCLUSIONS

AD currently affects 5.8 million persons in the US, and is a common cause of dementia which is usually accompanied by other neuropathology. The cause of dementia can be diagnosed by medical history, cognitive and physical examination, laboratory testing, and brain imaging. Management should include both non-pharmacologic approaches with cognitive, physical, and social activities, and pharmacologic approaches such as with an acetylcholinesterase inhibitor for AD, although efficacy of treatments remains limited.

Supplementary Material

Supplemental material, acknowledgements.

This study was supported by the National Institutes of Health, grant numbers P30 AG010161, R01 AG040039, R01 NS084965, and RF1 AG059621; the Health Resources and Services Administration for HRSA-15-057; and the Illinois Department of Public Health. The study funders had no role in the design or conduct of the study; collection, management, analysis, or interpretation of the data; preparation, review, or approval of the manuscript, or decision to submit the manuscript for publication.

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Case Report of a 63-Year-Old Patient With Alzheimer Disease and a Novel Presenilin 2 Mutation

Wells, Jennie L. BSc, MSc, MD, FACP, FRCPC, CCRP *,† ; Pasternak, Stephen H. MD, PhD, FRCPC †,‡,§

* Department of Medicine, Division of Geriatric Medicine, Schulich School of Medicine and Dentistry, Western University

† St. Joseph’s Health Care London—Parkwood Institute

‡ Molecular Medicine Research Group, Robarts Research Institute

§ Department of Clinical Neurological Sciences, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada

The authors declare no conflicts of interest.

Reprints: Jennie L. Wells, BSc, MSc, MD, FACP, FRCPC, CCRP, Department of Medicine, Division of Geriatric Medicine, St. Joseph’s Health Care London—Parkwood Institute, Room A2-129, P.O. Box 5777 STN B, London, ON, Canada N6A 4V2 (e-mail: [email protected] ).

This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0/

Early onset Alzheimer disease (EOAD) is a neurodegenerative dementing disorder that is relatively rare (<1% of all Alzheimer cases). Various genetic mutations of the presenilin 1 ( PSEN1 ) and presenilin 2 ( PSEN2 ) as well as the amyloid precursor protein (APP) gene have been implicated. Mutations of PSEN1 and PSEN2 alter γ-secretase enzyme that cleaves APP resulting in increase in the relative amount of the more amyloidogenic Aβ42 that is produced. 1

PSEN2 has been less studied than PSEN1 and fewer mutations are known. Here, we report a case of a 63-year-old woman (at the time of death) with the clinical history consistent with Alzheimer D, an autopsy with brain histopathology supporting Alzheimer disease (AD), congophylic angiopathy, and Lewy Body pathology, and whose medical genetic testing reveals a novel PSEN2 mutation of adenosine replacing cytosine at codon 222, nucleotide position 665 (lysine replacing threonine) that has never been previously reported. This suggests that genetic testing may be useful in older patients with mixed pathology.

CASE REPORT

The patient was referred to our specialty memory clinic at the age of 58 with a 2-year history of repetitiveness, memory loss, and executive function loss. Magnetic resonance imaging scan at age 58 revealed mild generalized cortical atrophy. She is white with 2 years of postsecondary education. Retirement at age 48 from employment as a manager in telecommunications company was because family finances allowed and not because of cognitive challenges with work. Progressive cognitive decline was evident by the report of deficits in instrumental activities of daily living performance over the past 9 months before her initial consultation in the memory clinic. Word finding and literacy skills were noted to have deteriorated in the preceding 6 months according to her spouse. Examples of functional losses were being slower in processing and carrying out instructions, not knowing how to turn off the stove, and becoming unable to assist in boat docking which was the couple’s pastime. She stopped driving a motor vehicle about 6 months before her memory clinic consultation. Her past medical history was relevant for hypercholesterolemia and vitamin D deficiency. She had no surgical history. She had no history of smoking, alcohol, or other drug misuse. Laboratory screening was normal. There was no first-degree family history of presenile dementia. Neurocognitive assessment at the first clinic visit revealed a Mini Mental State Examination (MMSE) score of 14/30; poor verbal fluency (patient was able to produce only 5 animal names and 1 F-word in 1 min) as well as poor visuospatial and executive skills ( Fig. 1 ). She had fluent speech without semantic deficits. Her neurological examination was pertinent for normal muscle tone and power, mild ideomotor apraxia on performing commands for motor tasks with no suggestion of cerebellar dysfunction, normal gait, no frontal release signs. Her speech was fluent with obvious word finding difficulties but with no phonemic or semantic paraphrasic errors. Her general physical examination was unremarkable without evidence of presenile cataracts. She had normal hearing. There was no evidence of depression or psychotic symptoms.

At the time of the initial assessment, her mother was deceased at age 79 after a hip fracture with a history long-term smoking and idiopathic pulmonary fibrosis. Her family believes that there is possible German and Danish descent on her father’s side. Her father was alive and well at age 80 at the time of her presentation with a history coronary artery disease. He is still alive and well with no functional or cognitive concerns at age 87 at the time of writing this report. Her paternal grandfather died at approximately age 33 of appendicitis with her paternal grandmother living with mild memory loss but without known dementia or motor symptoms until age 76, dying after complications of abdominal surgery. Her paternal uncle was diagnosed with Parkinson disease in his 40s and died at age 58. Her maternal grandmother was reported to be functionally intact, but mildly forgetful at the time of her death at age 89. The maternal grandfather had multiple myocardial infarctions and died of congestive heart failure at age 75. She was the eldest of 4 siblings (ages 44 to 56 at the time of presentation); none had cognitive problems. She had no children.

Because of her young age and clinical presentation with no personality changes, language or motor change, nor fluctuations, EOAD was the most likely clinical diagnosis. As visuospatial challenges were marked at her first visit and poor depth perception developing over time, posterior cortical variant of AD was also on the differential as was atypical presentation of frontotemporal dementias. Without fluctuations, Parkinsonism, falls, hallucinations, or altered attention, Lewy Body dementia was deemed unlikely. After treatment with a cholinesterase inhibitor, her MMSE improved to 18/30, tested 15 months later with stability in function. Verbal fluency improved marginally with 7 animals and 3 F-words. After an additional 18 months, function and cognition declined (MMSE=13/30) so memantine was added. The stabilizing response to the cholinesterase inhibitor added some degree of confidence to the EOAD diagnosis. In the subsequent 4 years, she continued to decline in cognition and function such that admission to a care facility was required with associated total dependence for basic activities of daily living. Noted by family before transfer to the long-term care facility were episodic possible hallucinations. It was challenging to know if what was described was misinterpretation of objects in view or a true hallucination. During this time, she developed muscle rigidity, motor apraxias, worsening perceptual, and language skills and became dependent for all activities of daily livings. At the fourth year of treatment, occasional myoclonus was noted. She was a 1 person assist for walking because of increased risk of falls. After 1 year in the care home, she was admitted to the acute care hospital in respiratory distress. CT brain imaging during that admission revealed marked generalized global cortical atrophy and marked hippocampal atrophy ( Fig. 2 ). She died at age 63 of pneumonia. An autopsy was performed confirming the cause of death and her diagnosis of AD, showing numerous plaques and tangles with congophilic amyloid angiopathy. In addition, there was prominent Lewy Body pathology noted in the amygdala.

Three years before her death informed consent was obtained from the patient and family to perform medical genetic testing for EOAD. The standard panel offered by the laboratory was selected and included PSEN1 , PSEN2 , APP, and apoE analysis. Tests related to genes related to frontotemporal dementia were not requested based on clinical presentation and clinical judgement. This was carried out with blood samples and not cerebrospinal fluid because of patient, family, and health provider preference. The results revealed a novel PSEN2 mutation with an adenosine replacing cytosine at nucleotide position 665, codon 222 [amino acid substation of lysine for threonine at position 221 (L221T)]. This PSEN2 variant was noted to be novel to the laboratory’s database, noting that models predicted that this variant is likely pathogenic. The other notable potentially significant genetic finding is the apoliprotein E genotype was Є 3/4 .

β-amyloid (Aβ) is a 38 to 43 amino acid peptide that aggregates in AD forming toxic soluble oligomers and insoluble amyloid fibrils which form plaques. Aβ is produced by the cleavage of the APP first by an α-secretase, which produces a 99 amino acid C-terminal fragment of APP, and then at a variable “gamma” position by the γ-secretase which releases the Aβ peptide itself. It is this second γ-cleavage which determines the length and therefore the pathogenicity of the Aβ peptides, with 42 amino acid form of Aβ having a high propensity to aggregate and being more toxic.

The γ-secretase is composed of at least 4 proteins, mAph1, PEN2, nicastrin, and presenilin . Of these proteins, presenilin has 2 distinct isoforms ( PSEN1 and PSEN2 ), which contain the catalytic site responsible for the γ-cleavage. PSEN mutants are the most common genetic cause of AD with 247 mutations described in PSEN1 and 48 mutations described in PSEN2 (Alzgene database; www.alzforum.org/mutations ). PSEN2 mutations are reported to be associated with AD of both early onset and variable age onset as well as with other neurodegenerative disorders such as Lewy Body dementia, frontotemporal dementia, Parkinson dementia, and posterior cortical atrophy. 2–4 In addition, PSEN2 has associations with breast cancer and dilated cardiomyopathy. 3

PSEN2 mutants are believed to alter the γ-secretase cleavage of APP increasing the relative amount of the more toxic Aβ42. The mean age of onset in PSEN2 mutations, is 55.3 years but the range of onset is surprisingly wide, spanning 39 to 83 years. Over 52% of cases are over 60 years. All cases have extensive amyloid plaque and neurofibrillary tangles, and many have extensive alpha-synuclein pathology as well. 5

In considering the novelty of this reported PSEN2 mutation, a literature search of Medline, the Alzgene genetic database of PSEN2 and the Alzheimer Disease and Frontotemporal Dementia Mutation Databases (AD&FTMD) were completed ( www.molgen.vib-ua.be/ADMutations ). The mutation presented here (L221T) has never been described before.

Although this mutation has not been described, we believe that it is highly likely to be pathogenic. This mutation is not conservative, as it replaces a lysine residue which is positively charged with threonine which is an uncharged polar, hydrophilic amino acid. The mutation itself occurs in a small cytoplasmic loop between transmembrane domain 4 and 5, which is conserved in the PSEN1 gene, and in PSEN2 is highly conserved across vertebrates, including birds and zebrafish all the way to Caenorhabditis elegans , but differs in Drosophila melanogaster (fruit fly) ( Fig. 3 ). We examined this mutation using several computer algorithms which examine the likelihood that a mutation will not be tolerated. Both SIFT ( http://sift.bii.a-star.edu.sg ) and PolyPhen-2.2.2 (HumVar) ( www.bork.embl-heidelberg.de/PolyPhen ) predicts that this variant is pathogenic. Interestingly, it is noted that PSEN1 mutations after amino acid 200 develop amyloid angiopathy. 5,7

This patient also had an additional risk factor for AD, being a heterozygote for the apoЄ4 allele. Among other mechanisms, its presence reduces clearance of Aβ42 from the brain and increases glial activation. 8 Although the apoЄ4 allele is known to lower the age of onset of dementia in late onset AD, it has not been clearly shown to influence age of onset of EOAD in a limited case series. 9 It should be noted that heterozygote state may have contributed to an acceleration of her course given the known metabolism of apoЄ4 and its association with accelerated cerebral amyloid and known reduction in age of onset. 10

Given that there is no definite family history of autosomal dominant early onset dementia, it is likely that her PSEN2 mutation was a new random event. With the unusually wide age of onset it is conceivable that one of her parents could still harbor this PSEN2 mutation. The patient’s father, however, is currently 87 and living independently at the time of writing this manuscript, making him highly unlikely to be an EOAD carrier. Nonpaternity is an alternate explanation for the lack of known first-degree relative with EOAD; however, this is deemed unlikely by the family member who provided the supplemental history. Her mother died at age 79, so she could conceivably carry our mutation but we do not have access to this genetic material. Without extensive testing of many family members it would be impossible to speculate about autosomal recessive form of gene expression. In addition, the genetic testing requested was limited to presenilins , APP, and apoE mutations. Danish heritage may add Familial Danish dementia as a remote consideration; however, Familial Danish dementia has a much different clinical presentation with long tract signs, cerebellar dysfunction, onset in the fourth decade as well as hearing loss and cataracts at a young age. 11 This disease has high autosomal dominant penetration which also makes it less likely in the patient’s context. This specific gene (chromosome 13) was not tested. The autopsy findings do not support this possibility. There are reports of Familial AD pedigrees in Germany, including a Volga pedigree with PSEN141I mutation in exon 5, but this is clearly separate from our mutation which is in exon 7. Our mutation was also not observed in a recent cohort of 23 German individuals with EOAD which underwent whole genome sequencing, but did find 2 carriers of the Volga pedigree. It is also possible that both the PSEN2 mutation and the ApoE genotype contributed to her disease and early onset presentation. This case illustrates the multiple pathology types which occur in individuals bearing PSEN2 mutations, and highlights the later ages in which patients can present with PSEN2 mutations. 12

ACKNOWLEDGMENT

The authors acknowledge Gwyneth Duhn, RN, BNSc, MSc, for her support of this paper.

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Case Study 1: A 55-Year-Old Woman With Progressive Cognitive, Perceptual, and Motor Impairments

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CASE PRESENTATION

What are diagnostic considerations based on the history how might a clinical examination help to narrow the differential diagnosis.

How Does the Examination Contribute to Our Understanding of Diagnostic Considerations? What Additional Tests or Studies Are Indicated?

Considering This Additional Data, What Would Be an Appropriate Diagnostic Formulation?

Does information about the longitudinal course of her illness alter the formulation about the most likely underlying neuropathological process, neuropathology.

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• Posterior Cortical Atrophy
• Corticobasal Syndrome
• Atypical Alzheimer Disease
• Network Degeneration

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Understanding the Link Between Depression and Memory Loss

• Research on Link
• Memory and Depression
• Other Causes
• When to See a Provider

There is a link between depression and short-term memory loss. This is sometimes called pseudodementia because it can be confused with dementia although the memory loss is actually due to depression.

Stress and anxiety can lead to poor memory. Other symptoms of depression include low mood, lack of energy, changes in sleep patterns and appetite, and loss of interest.

Viktoriya Skorikova / Getty Images

Can Depression Cause Memory Loss? What the Research Says

Depression can make you lose memory . A 2024 study of more than 8,000 individuals examined depression and memory symptoms over the course of 16 years.

It found a bidirectional relationship between depression and memory loss. This means that participants who had more severe depression had greater memory loss, and those with a steeper change in memory loss also had a more rapid increase in depressive symptoms.

Research has also found that memory loss and other cognitive deficits associated with depression can persist even after an episode of depression has resolved. They can also worsen with repeated episodes of depression. This is just one reason that treating depression is so important.

Working memory,  long-term memory,  and selective attention seem to be particularly affected by depression. Procedural memory, or the memory for certain skills like riding a bike or brushing your teeth, seems to be unaffected.

People who are depressed tend to show poorer memory for positive events, better memory for negative events, and overall impaired recollection.

The reasons behind this are not well understood. However, researchers believe that memory issues with depression are linked to the biological impacts of chronic stress on brain structures related to memory. Such structures as the hippocampus and amygdala , and neurons that produce the neurotransmitter dopamine (the "feel-good" hormone) in the brain.

Is Memory Loss a Sign of Depression?

Memory loss could be a sign of depression. However, memory loss associated with depression can sometimes look like dementia to an outsider. Naturally, you may be concerned about what could be causing this change.

Some notable differences between memory loss in depression and dementia are listed below.

Aware of their memory change and concerned by it

Slow or minor change in memory

Not typically disoriented

Difficulty concentrating, a feeling of "brain fog"

Typically no issues with writing, communication, vision, or motor skills

Unaware or indifferent to memory change

Rapid change in memory

Often disoriented to person, time, or place

Trouble with short-term memory

Issues with writing, communicating, vision, and motor skills

Other Causes of Memory Loss

Mental health conditions besides depression can also contribute to memory loss. These include:

• Bipolar disorder
• Post-traumatic stress disorder (PTSD)
• Schizophrenia

Other causes of memory loss include:

• Brain surgery
• Brain tumor
• Cancer treatments such as brain radiation or chemotherapy
• Hydrocephalus
• Low levels of vitamin B12
• Medications like sleep aids and pain medicinene
• Multiple sclerosis
• Uncontrolled epilepsy

How Memory Loss Is Diagnosed

Diagnosis of memory loss can be a complicated process because there are many possible causes. Your healthcare provider will likely first ask about your medical history and any symptoms. Due to the nature of memory loss, they may also ask your family or friends for their input.

Based on those answers, your healthcare provider will likely run a series of diagnostic tests, which may include:

• Blood tests, for vitamin deficiencies or specific medical conditions
• Cerebral angiography (images blood vessels in the brain)
• Cognitive tests , for example, the Montreal Cognitive Assessment (MoCA)
• Computed tomography (CT) or magnetic resonance imaging (MRI) scans
• Electroencephalogram (EEG) (measures brain electrical activity)
• Lumbar puncture (taking a sample of fluid from around the spinal cord in the lower back)

How to Manage Memory Loss and Depression

Memory greatly affects day-to-day functioning, communication, and the ability to care for ourselves. If your short-term memory is impacted by depression, be sure to take your medication and follow your treatment plan. The following memory strategies may also help:

• Keep notes on your phone or a notepad about things you need to do or remember.
• Set alarms on your phone for when you need to be ready for an event.
• Keep a digital or paper calendar to remember important events.
• Mentally review and repeat important information immediately after you learn it.
• Be patient with yourself.

If you have symptoms of depression , see a healthcare provider for diagnosis and treatment. Taking certain lifestyle changes can also help you manage your depression symptoms, which may be beneficial to your memory over time. Some ways to cope with depression include:

• Get regular exercise for at least 30 minutes five times per week.
• Eat a healthy diet.
• Make an effort to socialize and reach out to people who are important to you.
• Stick to a routine.
• Try stress reduction techniques like meditation, yoga, sound baths, or breathing techniques.
• Write down your goals.

When to Contact a Healthcare Provider

If you are experiencing memory loss , depression symptoms , or both, consider contacting a healthcare provider.

Any memory loss should be taken seriously to get an accurate diagnosis and prevent further potential memory loss. The same goes for depression, which is a serious mental health condition but highly treatable.

Help in a Mental Health Emergency

If   you or someone you know is experiencing a mental health crisis, text or call  988  to reach the 988 Suicide & Crisis Lifeline. When online, visit  988lifeline.org  for its chat line. The Substance Abuse and Mental Health Services Administration (SAMHSA) can also help by calling  800-662-HELP (4357) .

Depression can lead to trouble with memory, in particular a person's working memory, and their ability to encode memories into long-term memories. They also tend to remember negative events more strongly than positive events. Treating depression can help prevent future episodes and worsening memory.

Harvard Health Publishing. Is it dementia or depression?

Yin J, John A, Cadar D. Bidirectional associations of depressive symptoms and cognitive function over time .  JAMA Netw Open . 2024;7(6):e2416305-e2416305. doi:10.1001/jamanetworkopen.2024.16305

Semkovska M, Quinlivan L, O’Grady T, et al. Cognitive function following a major depressive episode: a systematic review and meta-analysis .  The Lancet Psychiatry . 2019;6(10):851-861. doi: 10.1016/S2215-0366(19)30291-3

Dillon DG, Pizzagalli DA. Mechanisms of memory disruption in depression.   Trends Neurosci . 2018;41(3):137-149. doi:10.1016/j.tins.2017.12.006

Penn Medicine. Memory loss .

Harvard Health Publishing. Stuck in a brain fog? Look in your medicine cabinet.

National Institute on Aging. Memory problems, forgetfulness, and aging .

Sarris J, O'Neil A, Coulson CE, Schweitzer I, Berk M. Lifestyle medicine for depression . BMC Psychiatry . 2014;14:107. doi:10.1186/1471-244X-14-107

By Sarah Bence, OTR/L Bence is an occupational therapist with a range of work experience in mental healthcare settings. She is living with celiac disease and endometriosis.

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Assessing Cognitive Impairment in Older Patients

On this page:

Why is it important to assess cognitive impairment in older adults?

Benefits of early assessment, when is assessment indicated, how can physicians and staff find time for assessment, how to assess for cognitive impairment, what to do after assessment, points to remember.

As a primary care practitioner, you likely have long-established relationships with some of your patients and are in an ideal position to observe potential signs of a cognitive problem. You and your staff are often the first to address a patient’s or family’s concerns about cognitive as well as behavioral and functional changes that may have already affected their lives and resulted in, for example, a motor vehicle accident or being the victim of identity theft or financial fraud. ( 1 , 2 ) It’s important to take concerns seriously and to assess the person as early as possible to determine the potential cause of impairment. This quick guide features information about assessing cognitive, behavioral, and functional changes in older adults.

It’s important to address any changes in an older person’s memory, language abilities, or personality as these may reflect a neurodegenerative disease process that may either be due to a reversible cause or become more serious. Whether memory or other cognition concerns are reported by the patient or a family member, or directly observed by you, the issues should be noted in the patient’s chart and followed up with a cognitive, behavioral and/or functional assessment.

Cognitive impairment in older adults has a variety of possible causes, including medication side effects; metabolic and/or endocrine dysfunction; delirium due to illness (such as a urinary tract or COVID-19 infection); depression; and dementia, including Alzheimer’s disease , vascular dementia, Lewy body dementia, and frontotemporal disorders. Some causes, like medication side effects and depression, can be reversed or improved with treatment. Others, such as Alzheimer’s, cannot be reversed, but symptoms may be treatable for a period of time. It is important to help prepare patients and their families for additional changes that come as cognitive impairment progresses.

Many people who are developing dementia or already have it do not receive a diagnosis. One study found that more than 50% of patients with dementia had not received a clinical cognitive evaluation by a physician. ( 3 ) Another study showed that physicians were unaware of cognitive impairment in more than 40% of their cognitively impaired patients. ( 4 ) Yet another analysis looking at undetected dementia globally found the U.S. rate to be 61%. ( 5 ) The problem of underdiagnosis is even more pronounced in underserved populations and in those with lower educational attainment. ( 6 , 7 ) The failure to evaluate memory or cognitive complaints is likely to hinder treatment of underlying disease and comorbid conditions, and may present safety issues for the patient and others. ( 8 , 9 ) In many cases, the cognitive problem will worsen over time and may lead to preventable hospitalizations. ( 2 , 8 , 10 , 11 )

Some older people have mild cognitive impairment (MCI). People living with MCI have more memory problems than is normal for their age, but their symptoms do not interfere significantly with their everyday lives. Older people with MCI are at greater risk for developing Alzheimer’s, but not all of them do. Some may even go back to normal cognition. It is important to determine the cause of the impairment to anticipate future needs, address any reversible causes, and try to mediate modifiable risk factors.

Most people with memory, other cognitive, or behavioral complaints want a diagnosis to understand the nature of their problem and to know what to expect. ( 10 , 12 , 13 , 14 , 15 ) In a survey conducted by the Alzheimer’s Association of 2,434 U.S. adults age 18 and older, 85% of respondents said they would want to know early if they had Alzheimer’s. Reasons for wanting to know included planning for the future, allowing for earlier treatment of symptoms, taking steps to preserve existing cognitive function, and being able to understand what is happening. ( 16 )

Some people are reluctant to mention concerns about memory or other cognitive or behavioral issues because they fear a diagnosis of dementia and how the disease will impact their lives in the future. In these cases, a primary care provider can explain the benefits of finding out what may be causing the person’s health concerns.

While pharmacological treatment options for Alzheimer’s-related memory loss and other cognitive symptoms are limited, there are medicines approved by the U.S. Food and Drug Administration to help manage symptoms, as well as newer medicines granted Accelerated Approval to treat Alzheimer’s. Learn more about these medications in NIA’s How Is Alzheimer’s Disease Treated?

In addition, there are non-drug strategies that can promote physical and emotional comfort. Assessing cognitive impairment and identifying its cause, particularly at an early stage, is beneficial so patients and families can learn about these strategies and develop a care plan in concert with their health care providers.

Clinical trials or other research studies are also an option for people with cognitive impairment. Patients may be interested in participating in clinical trials not only for themselves but also because of the potential to help future generations. Visit the Alzheimers.gov Clinical Trials Finder for more information.

If assessment is negative, meaning there is no evidence of cognitive impairment: Concerns may be alleviated, at least at that point in time, and it is useful for both the person with concerns as well as the clinician to have a baseline for future assessments.

If assessment is positive and further evaluation is warranted: The patient and physician can take the next step of identifying the cause of impairment because medical conditions such as tumors, vitamin deficiencies, or medication side effects can also cause serious memory problems that resemble dementia. The results of an evaluation may lead to:

• Treating the underlying disease or health condition
• Managing comorbid conditions and medications more effectively and appropriately for the diagnosis
• Averting or addressing potential safety issues
• Allowing the patient to create or update advance directives and plan long-term care
• Ensuring the patient has support services and a care network to help with medical, legal, and financial concerns
• Working with the patient and their caregiver to develop strategies to improve quality of life, modify the patient’s lifestyle, make home safety modifications, and manage emotions related to the dementia diagnosis
• Referring the patient to a geriatrician, neurologist, geriatric psychiatrist, neuropsychologist, geriatric social worker, geriatric counselor, mental health counselor, or substance abuse professional for a more specific diagnosis or help with care management
• Ensuring the caregiver receives appropriate information, referrals, and support for coping with a dementia diagnosis, managing stress, and preparing for expected changes as well as making the best use of intact abilities
• Encouraging participation in clinical research, including clinical trials and studies

Learn more at Alzheimers.gov/clinical-trials and Talking With Your Patients About Alzheimer’s and Related Dementias Clinical Trials .

In its 2020 review and recommendation regarding routine screening for cognitive impairment in adults 65 years old and older, the U.S. Preventive Services Task Force noted that “although there is insufficient evidence to recommend for or against screening for cognitive impairment, there may be important reasons to identify cognitive impairment early. Clinicians should remain alert to early signs or symptoms of cognitive impairment (e.g., problems with memory or language) and evaluate the individual as appropriate.” ( 17 )

Other risk factors that could indicate the need for dementia screening include: history of type 2 diabetes, stroke, depression, trouble managing money or medications, and being older than 80. ( 18 ) Tools such as the Dementia Screening Indicator can help guide clinician decisions about when it may be appropriate to screen for cognitive impairment in the primary care setting. ( 18 )

Trained staff need only 10 minutes or less to initially assess a patient for cognitive impairment. While results alone are insufficient to diagnose dementia, they are an important first step. The AD8 , QDRS , and Mini-Cog are among many possible tools and some can be filled out by the person or the caregiver while in the waiting room.

Disclaimer: NIA does not endorse any specific cognitive assessment tools. The selection of an assessment tool depends on a variety of factors, including the setting, target population age and demographics, language, and expertise of the administrator. Research is underway to create and validate new tools for cognitive assessment in primary care settings. For more information, visit Cognitive Assessment Considerations: Understanding the Evidence .

Assessment for cognitive impairment can be performed at any visit but is a required component of the Medicare Annual Wellness Visit . ( 8 , 19 ) Coverage for yearly wellness visits, and importantly, for follow-up visits for cognitive assessment and care plan services , is available to patients with Medicare Part B coverage.

Visit the Centers for Medicare & Medicaid Services (CMS) for more information on cognitive assessment and care plan services (code 99483), including what it covers and how to bill for it. CMS also created a related educational video for health care providers . The Alzheimer’s Association also offers information on cognitive assessment and care planning services .

Positive results from a brief assessment warrant further evaluation. A combination of neuropsychological evaluation, including self- and informant-reports from a person who has frequent contact with the person being evaluated, such as a spouse or other care provider, is the best way to assess cognitive impairment more fully. ( 20 )

A primary care provider may conduct an evaluation or refer to a specialist, such as a geriatrician, neurologist, geriatric psychiatrist, or neuropsychologist. If available, a local memory disorders clinic or an NIA-funded Alzheimer’s Disease Research Center may also accept referrals.

Genetic testing, neuroimaging, and biomarker testing have been recommended for limited clinical uses. ( 2 , 21 ) These tests are primarily conducted in research settings and may require consultation with the medical provider, a counselor, and the family and caregivers as there are complex ethical, legal, and social implications that should be considered. In addition, some new Alzheimer’s medications may require or warrant the confirmation of beta-amyloid plaques before prescribing, as well as brain imaging during treatment to evaluate for amyloid-related imaging abnormalities (ARIA).

Interviews to assess memory, behavior, mood, and functional status of the patient are best conducted without family members or companions present who may prompt the person’s responses. However, family members or close companions can also be good sources of information. It can be beneficial to speak with them while the patient is in the room, as well as privately to allow for a more candid discussion. Per HIPAA regulations, the patient should give permission in advance. Brief, easy-to-administer tools, such as the Short IQCODE (PDF, 1.9M), the AD8 , or the QDRS for the caregiver are available.

Note that people who are only mildly impaired may be adept at covering up their cognitive decline and reluctant to address the problem. In some cases, patients may not have insight into their cognitive and functional problems due to the nature of their illness.

Additional resources are available to help health care teams in their detection of cognitive impairment and support of patients. For example, the American Academy of Family Physicians developed a Cognitive Care Kit , and the Gerontological Society of America developed the GSA KAER Toolkit for Primary Care Teams .

For more information on cognitive assessment tools, and other resources for health professionals, visit Alzheimer’s and Related Dementias Resources for Professionals .

After assessment for cognitive impairment is complete, take time to reflect on your relationship with the person to determine the best way to deliver the results.

Some people may prefer a cautious, reserved explanation. Other patients may prefer more precise language and appreciate when specific words, such as “Alzheimer’s disease,” are referenced.

The American College of Physicians Foundation and Alzheimer’s Association have produced an 11-minute video, Disclosing an Alzheimer’s Diagnosis , that may be helpful. Written materials can also be helpful: NIA’s Alzheimer’s and related Dementias Education and Referral Center has free tools and publications you can give to your patients, including Next Steps After an Alzheimer’s Diagnosis . Local resources can also be found using the Eldercare Locator .

Communicating with older patients

If possible, schedule additional time for the appointment or a follow-up, so that you can listen and respond to the patient’s and caregiver’s concerns. Ask the patient if there is a family member or friend who can help with medical, legal, and financial concerns going forward. Suggest making these arrangements as early as possible and ensure that the patient has given you formal authorization to include the caregiver in the conversation about your patient’s care. Keep that person’s name and contact information in your notes for future reference.

Informing family members or others that the patient may have Alzheimer’s, or any cognitive impairment, may be done in a telephone conference or group meeting, which should be arranged with the consent of the patient. It is the patient’s choice on how, whether, and with whom they want to share this information. Let everyone know that you will continue to be available for care, information, guidance, and support. And provide them with resources, such as the 24/7 helpline, in writing. Make them aware that there are support groups and other ways to get help.

Consider how your practice can coordinate and integrate care for the patient and caregiver across the many specialists and services that will be involved. Nonprofit support and community organizations can provide information about planning, social services, and care.

Learn more in Caring for Older Patients With Cognitive Impairment .

Communicating with caregivers

All caregivers face challenges, but these challenges are compounded for people caring for patients with Alzheimer’s or other forms of cognitive impairment. Here are some approaches that can be especially useful when communicating with caregivers:

• Explain that much can be done to improve the patient’s quality of life. Measures such as modifications in daily routine and medications may help. If the patient is in the later stages of dementia, consider bringing in a palliative care consultant to help with symptom management.
• Provide information about the consumer resources and services available from local organizations, as well as support groups.
• Encourage caregivers to get regular respite , especially when patients require constant attention. Ask if the caregiver, who is at considerable risk for stress-related disorders, is receiving adequate support. Encourage the caregiver to speak with their own health care provider. They may have trouble recognizing their own needs when they are so focused on their loved one; assure them that it is crucial to take care of themselves in order to best support their loved one.
• The individual, family members, or others express concerns about changes in the person’s memory, thinking, or behavior
• As the health care provider, you observe problems/changes in the patient’s memory, thinking, or behavior
• Brief assessments are available and can be used in an office visit.
• Assessment for cognitive impairment is a required component of the Medicare Annual Wellness Visit .
• People, particularly those who express a concern, likely want to know what the underlying problem is. It is important to emphasize that, no matter what the diagnosis is, there are options for support and care for the person and their caregivers.
• It's important to talk with the patient and caregiver about potential challenges and how to cope with their results.
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This content is provided by the NIH National Institute on Aging (NIA). NIA scientists and other experts review this content to ensure it is accurate and up to date.

Content reviewed: April 16, 2023

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