Archives for April 2017

Caregiver Stress and Burnout: Tips for Regaining Your Energy, Optimism, and Hope

(HelpGuide) The demands of caregiving can be overwhelming, especially if you feel you have little control over the situation or you’re in over your head. If the stress of caregiving is left unchecked, it can take a toll on your health, relationships, and state of mind—eventually leading to burnout.

When you’re burned out, it’s tough to do anything, let alone look after someone else. That’s why taking care of yourself isn’t a luxury—it’s a necessity. Read on for tips on how to rein in the stress in your life and regain balance, joy, and hope.

What Do You Need to Know?

Caring for a loved one can be very rewarding, but it also involves many stressors. Caregiver stress can be particularly damaging, since it is typically a chronic, long-term challenge. You may face years or even decades of caregiving responsibilities. It can be particularly disheartening when there’s no hope that your family member will get better.

If you don’t get the physical and emotional support your need, the stress of caregiving leaves you vulnerable to a wide range of problems, including depression, anxiety, and burnout. And when you get to that point, both you and the person you’re caring for suffer. That’s why managing the stress levels in your life is just as important as making sure your family member gets to his doctor’s appointment or takes her medication on time.

Signs and Symptoms of Caregiver Stress and Burnout

Learning to recognize the signs of caregiver stress and burnout is the first step to dealing with the problem.

Common Signs and Symptoms of Caregiver Stress

  • Anxiety, depression, irritability
  • Feeling tired and run down
  • Difficulty sleeping
  • Overreacting to minor nuisances
  • New or worsening health problems
  • Trouble concentrating
  • Feeling increasingly resentful
  • Drinking, smoking, or eating more
  • Neglecting responsibilities
  • Cutting back on leisure activities

Common Signs and Symptoms of Caregiver Burnout

  • You have much less energy than you once had
  • It seems like you catch every cold or flu that’s going around
  • You’re constantly exhausted, even after sleeping or taking a break
  • You neglect your own needs, either because you’re too busy or you don’t care anymore
  • Your life revolves around caregiving, but it gives you little satisfaction
  • You have trouble relaxing, even when help is available
  • You’re increasingly impatient and irritable with the person you’re caring for
  • You feel helpless and hopeless

Once you burn out, caregiving is no longer a healthy option for either you or the person you’re caring for. So it’s important to watch for the warning signs of caregiver burnout and take action right away when you recognize the problem.

Don’t let caregiving take over your whole life. It’s easier to accept a difficult situation when there are other areas of your life that are rewarding. Invest in things that give you meaning and purpose—whether it’s your family, church, a favorite hobby, or your career. Read on for some additional tips to lighten the load:

Find Ways to Feel Empowered

Feeling powerless is the number one contributor to burnout and depression. And it’s an easy trap to fall into as a caregiver, especially if you feel stuck in a role you didn’t expect or helpless to change things for the better. But no matter the situation, you aren’t powerless. This is especially true when it comes to your state of mind. You can’t always get the extra time, money, or physical assistance you’d like, but you can always get more happiness and hope.

Embrace your caregiving choice. Acknowledge that, despite any resentments or burdens you feel, you have made a conscious choice to provide care. Focus on the positive reasons behind that choice. Perhaps you provide care to repay your parent for the care they gave you growing up. Or maybe it’s because or your values or the example you want to set for your children. These deep, meaningful motivations can help sustain you through difficult times.

Focus on the things you can control. You can’t wish your mother’s cancer away or force your brother to help out more. Rather than stressing out over things you can’t control, focus on the way you choose to react to problems.

Celebrate the small victories. If you start to feel discouraged, remind yourself that all your efforts matter. You don’t have to cure your loved one’s illness to make a difference. Don’t underestimate the importance of making your loved one feel more safe, comfortable, and loved!

Get the Appreciation You Need

Feeling appreciated can go a long way toward not only accepting a stressful situation, but enjoying life more. Studies show that caregivers who feel appreciated experience greater physical and emotional health. Caregiving actually makes them happier and healthier, despite its demands. But what can you do if the person you’re caring for is no longer able to feel or show their appreciation for your time and efforts?

Imagine how your loved one would respond if he or she was healthy. If he or she wasn’t preoccupied with illness or pain (or disabled by dementia), how would your loved one feel about the love and care you’re giving? Remind yourself that the person would express gratitude if he or she was able.

Applaud your own efforts. If you’re not getting external validation, find ways to acknowledge and reward yourself. Remind yourself of the good you’re doing. If you need something more concrete, try making a list of all the ways your caregiving is making a positive difference. Refer back to it when you start to feel low.

Talk to a supportive family member or friend. Positive reinforcement doesn’t have to come from the person you’re caring for. When you’re feeling unappreciated, turn to friends and family who will listen to you and acknowledge your efforts.

Ask for Help

Taking on all of the responsibilities of caregiving without regular breaks or assistance is a surefire recipe for burnout. Don’t try to do it all alone. Look into respite care. Or enlist friends and family who live near you to run errands, bring a hot meal, or “baby-sit” the care receiver so you can take a well-deserved break.

Tips for getting the caregiving help you need

Speak up. Don’t expect friends and family members to automatically know what you need or how you’re feeling. Be up front about what’s going on with you and the person you’re caring for. If you have concerns or thoughts about how to improve the situation, express them—even if you’re unsure how they’ll be received. Get a dialogue going.

Spread the responsibility. Try to get as many family members involved as possible. Even someone who lives far away can help. You may also want to divide up caregiving tasks. One person can take care of medical responsibilities, another with finances and bills, and another with groceries and errands, for example.

Set up a regular check-in. Ask a family member, friend, or volunteer from your church or senior center to call you on a set basis (every day, weekly, or how ever often you think you need it). This person can help you spread status updates and coordinate with other family members.

Say “yes” when someone offers assistance. Don’t be shy about accepting help. Let them feel good about supporting you. It’s smart to have a list ready of small tasks that others could easily take care of, such as picking up groceries or driving your loved one to an appointment.

Be willing to relinquish some control. Delegating is one thing. Trying to control every aspect of care is another. People will be less likely to help if you micromanage, give orders, or insist on doing things your way.

Give Yourself a Break

As a busy caregiver, leisure time may seem like an impossible luxury. But you owe it to yourself—as well as to the person you’re caring for—to carve it into your schedule. Give yourself permission to rest and to do things that you enjoy on a daily basis. You will be a better caregiver for it.

There’s a difference between being busy and being productive. If you’re not regularly taking time-off to de-stress and recharge your batteries, you’ll end up getting less done in the long run. After a break, you should feel more energetic and focused, so you’ll quickly make up for your relaxation time.

Maintain your personal relationships. Don’t let your friendships get lost in the shuffle of caregiving. These relationships will help sustain you and keep you positive. If it’s difficult to leave the house, invite friends over to visit with you over coffee, tea, or dinner.

Prioritize activities that bring you enjoyment. Make regular time for things that bring you happiness, whether it’s reading, working in the garden, tinkering in your workshop, knitting, playing with the dogs, or watching the game.

Find ways to pamper yourself. Small luxuries can go a long way in relieving stress and boosting your spirits. Light candles and take a long bath. Ask your hubby for a back rub. Get a manicure. Buy fresh flowers for the house. Or whatever makes you feel special.

Make yourself laugh. Laughter is an excellent antidote to stress—and a little goes a long way. Read a funny book, watch a comedy, or call a friend who makes you laugh. And whenever you can, try to find the humor in everyday situations.

Get out of the house. Seek out friends, family, and respite care providers to step in with caregiving so you can have some time away from the home.

Take Care of Your Health

Think of your body like a car. With the right fuel and proper maintenance, it will run reliably and well. Neglect its upkeep and it will start to give you trouble. Don’t add to the stress of your caregiving situation with avoidable health woes.

Keep on top of your doctor visits. It’s easy to forget about your own health when you’re busy with a loved one’s care. Don’t skip check-ups or medical appointments. You need to be healthy in order to take good care of your family member.

Exercise. When you’re stressed and tired, the last thing you feel like doing is exercising. But you’ll feel better afterwards. Exercise is a powerful stress reliever and mood enhancer. Aim for a minimum of 30 minutes on most days. When you exercise regularly, you’ll also find it boosts your energy level and helps you fight fatigue.

Meditate. A daily relaxation or meditation practice can help you relieve stress and boost feelings of joy and well-being. Try yoga, deep breathing, progressive muscle relaxation, or mindfulness meditation. Even a few minutes in the middle of an overwhelming day can help you feel more centered.

Eat well. Nourish your body with fresh fruit, vegetables, whole grains, beans, lean protein, and healthy fats such as nuts and olive oil. Unlike sugar and caffeine—which provide a quick pick-me-up and an even quicker crash—these foods will fuel you with steady energy.

Don’t skimp on sleep. Cutting back on time in bed is counterproductive—at least if your goal is to get more done. Most people need more sleep than they think they do (8 hours is the norm). When you get less, your mood, energy, productivity, and ability to handle stress will suffer.

Join a Support Group

A caregiver support group is a great way to share your troubles and find people who are going through the same experiences that you are living each day. If you can’t leave the house, many Internet groups are also available.

In most support groups, you’ll talk about your problems and listen to others talk; you’ll not only get help, but you’ll also be able to help others. Most important, you’ll find out that you’re not alone. You’ll feel better knowing that other people are in the same situation, and their knowledge can be invaluable, especially if they’re caring for someone with the same illness as you are.

Local vs. Online Support Groups for Caregivers
Local support groups: Online support groups:
People live near each other and meet in a given place each week or month. People are from all over the world and have similar interests or problems.
You get face-to-face contact and a chance to make new friends who live near you. You meet online, through email lists, websites, message boards, or social media.
The meetings get you out of the house, get you moving provide a social outlet, and reduce feelings of isolation. You can get support without leaving your house, which is good for people with limited mobility or transportation problems.
Meetings are at a set time. You will need to attend them regularly to get the full benefit of the group. You can access the group whenever it’s convenient for you or when you need help most.
Since the people in the support group are from your area, they’ll be more familiar with local resources and issues. If your problem is very unusual—a rare disease, for example—there may not be enough people for a local group, but there will always be enough people online.


To find a community support group, check the yellow pages, ask your doctor or hospital, or call a local organization that deals with the health problem you would like to address in a support group. To find an Internet support group, visit the website of an organization dedicated to the problem.

Related HelpGuide articles

Resources and References

Preventing family caregiver burnout

Preventing Caregiver Burnout – Part of a handbook and resource guide for caregivers in Florida. Examines the signs of caregiver burnout and how to handle it. Includes tips for caregivers who are themselves challenged by age or infirmity. (Area Agency on Aging of Pasco-Pinellas)

Taking Care of You: Self-Care for Family Caregivers – Learn about the effects of caregiving on your own well-being, and what you can do to care for yourself. (Family Caregiver Alliance)

How to Feel Empowered as a Caregiver – Tips from a caregiving specialist on how to avoid bitterness and burnout by waking up to options within your reach. (AARP Magazine)

Tips and support for family caregivers

Caregiver Toolbox – Explore helpful tips and resources for family caregivers. (Caregiver Action Network)

Caregiver Support – Find articles, tips, and resources for caregivers who need support. (

Find caregiver services and resources in the U.S.

Family Care Navigator  – A state-by-state resource intended to help you locate services for family caregivers and resources for older or disabled adults. (Family Caregiver Alliance)

Resources for Caregivers of Diverse Populations and Specific Age Groups – Find links to resources for caregivers of adults, children, individuals with disabilities and mental disorders, veterans, and more. (American Psychological Association)

Find caregiver services internationally

What Social Care Services are Available? – NHS services available to UK carers of disabled children and adults, including respite care. (NHS)

Caring for an Older Australian – For Australian residents, provides information and support services for older people, people with disabilities and those who provide care and services. (Australian Government)

Carers New Zealand – Offers help and advice for New Zealand carers, including guidance on respite care services. (Carers NZ)

Programs and Services (PDF) – Information on services for seniors in Canada, including in-home support.  (Government of Canada)

Get a Copy of This Article

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Authors: Melinda Smith, M.A. and Gina Kemp, M.A. Last updated: April 2017.

© All rights reserved.


Alzheimer’s Caregiving: Help with Home Care

(National Institutes of Health) Most people with Alzheimer’s disease are cared for at home by family members. Within families, caregiving is provided most often by wives and husbands, followed by daughters.

As Alzheimer’s disease gets worse, the person will need more and more care. Because of this, you will need more help. It’s okay to seek help whenever you need it.

Building a local support system is a key way to get help. This system might include a caregiver support group, the local chapter of the Alzheimer’s Association, family, friends, and faith groups. To learn where to get help in your community, contact

Various professional services can help with everyday care in the home of someone with Alzheimer’s disease. Medicare, Medicaid, and other health insurance plans may help pay for these services. Contact Eldercare Locator to find the services you need in your area by calling 1-800-677-1116 or visiting

Home Health Care Services

Home health care agencies send a home health aide or nurse to your home to help you care for a person with Alzheimer’s. They may come for a few hours or stay for 24 hours and are paid by the hour.

Some home health aides are better trained and supervised than others. Ask your doctor or other health care professional about good home health care services in your area. Get as much information as possible about a service before you sign an agreement. Also, ask for and check references

Here are some questions to ask before signing a home health care agreement.

  • Is your service licensed and accredited?
  • How much do your services cost?
  • What is included and not included in your services?
  • How many days a week and hours a day will an aide come to my home?
  • How do you check the background and experience of your home health aides?
  • How do you train your home health aides?
  • What types of emergency care can you provide?
  • Who do I contact if there is a problem?

Meal Services

Meal services bring hot meals to the person’s home or your home. The delivery staff does not feed the person. The person with Alzheimer’s disease must qualify for the service based on local guidelines. Some groups do not charge for their services. Others may charge a small fee. For information, call Eldercare Locator at 1-800-677-1116 or go to or Meals on Wheels at 703-548-5558.

Adult Day Care Services

Adult day care services provide a safe environment, activities, and staff who take care of the person with Alzheimer’s at their own facility. This provides a much-needed break for you. Many programs provide transportation between the person’s home and the facility.

Adult day care services generally charge by the hour. Most insurance plans do not cover these costs. To find adult day care services in your area, contact the National Adult Day Services Association at 1-877-745-1440.

Respite Services

Respite services provide short stays, from a few days to a few weeks, in a nursing home or other place for the person with Alzheimer’s disease. This care allows you to get a break or go on a vacation.

Respite services charge by the number of days or weeks that services are provided. Medicare or Medicaid may cover the cost of up to 5 days in a row of respite care in an inpatient facility. Most private insurance plans do not cover these costs. To find respite services in your community, visit the National Respite Locator Service at

Geriatric Care Managers

Geriatric care managers visit your home to assess your needs and suggest and arrange home-care services. They charge by the hour. Most insurance plans don’t cover these costs. To find a geriatric care manager, contact the National Association of Professional Geriatric Care Managers at 1-520-881-8008.

Mental Health Professionals and Social Workers

Mental health professionals and social workers help you deal with any stress you may be feeling. They help you understand feelings, such as anger, sadness, or feeling out of control. They can also help you make plans for unexpected or sudden events.

Mental health professionals charge by the hour. Medicare, Medicaid, and some private health insurance plans may cover some of these costs. Ask your health insurance plan which mental health counselors and services it covers. Then check with your doctor, local family service agencies, and community mental health agencies for referrals to counselors.

For more information, see Getting Help with Caregiving. You can order a print copy of this booklet by calling 1-800-222-2225 or visiting


National Institutes of Health


Exercise Boosts Brain Power In Over 50s

( Over the years, there has been much research on the potential cognitive benefits of exercise on mental performance in older adults. Overall, results have been inconclusive, but a new review takes a fresh look at the data.

As we age, our cognitive prowess tends to take a hit. Finding a way to halt or reduce this decline would make a huge difference to billions of lives.

One potential intervention is exercise, and many researchers have attempted to prove whether or not it can stave off age-related mental decline and neurodegenerative conditions.

Early research and meta-analyses demonstrated strong, positive results. Over recent years, however, published reviews on the topic have not reported such strong effects.

A Fresh Look at Aging and the Brain

According to the authors of the current paper, recently published reviews and meta-analyses have been inconclusive due to their restrictive inclusion criteria. For instance, some focused on just one type of exercise, while others limited their literature search to a narrow date range. The latest review is published this week in the British Journal of Sports Medicine.

The new analysis casts its net wide, looking at aerobic exercise, resistance training (such as weights), multicomponent exercise (including both resistance and aerobic training), tai chi, and yoga.

To fully assess the impact of these interventions, they looked at a raft of cognitive parameters. These include:

  • Brain capacity – global cognition
  • Attention – sustained alertness, including speed of information processing
  • Executive function – including goal-oriented behaviors
  • Memory – storage and retrieval
  • Working memory – the part of short-term memory that deals with immediate conscious perceptual and language processing

The team’s analysis showed that exercise improved the brain power of people aged 50 and older, regardless of their current brain health.

Prescribing Exercise

The results suggested that aerobic exercise enhanced cognitive abilities, while resistance training had a positive influence on executive function, memory, and working memory. According to the researchers, the results were strong enough to recommend prescribing both exercise types to bolster brain health in over 50s.

The next question asks how much exercise is needed. According to the analysis, a session of moderate to vigorous intensity lasting between 45 and 60 minutes was beneficial to brain health. In fact, any frequency had positive effects.

The authors conclude that:

“The findings suggest that an exercise program with components of both aerobic and resistance type training, of at least moderate intensity and at least 45 minutes per session, on as many days of the week as possible, is beneficial to cognitive function in adults aged over 50 years.”

Interestingly, tai chi was also found to improve cognitive capabilities. This is important because, as a low-impact exercise, it can be carried out by people who could not physically cope with more intense regimes. However, the authors point out that this conclusion was based on only a small number of studies, making the finding less robust.

How Exercise Might Reduce Cognitive Decline

Although there is a great deal of debate on this topic, scientists believe that there are a number of ways that exercise could help to stave off dementia and other degenerative neurological conditions.

According to the authors of the study, these include the promotion of neurogenesis (growth of new nervous tissue), angiogenesis (growth of new blood vessels), synaptic plasticity (the ability of synapses to strengthen or weaken over time), decreased pro-inflammatory processes, and reduced cellular damage due to oxidative stress.

Although the results will be widely heralded as positive, the authors note certain limitations to the study. For example, the analysis was limited to studies that looked at supervised exercise, and only those that were published in the English language.

If physical exercise really can stave off cognitive decline, it will benefit the population at large. This type of intervention can, of course, be cost effective or even free. If it has large-scale benefits, it could be a simple way of improving the lives of millions of older adults.

Even though the cognitive benefits may be small, the physical benefits of exercise are well established – so it is a win-win situation either way.


By Tim Newman

© 2004-2017 All rights reserved. MNT is the registered trademark of Healthline Media.


Low Levels Of “Memory Protein” Linked to Cognitive Decline in Alzheimer’s Disease

(Johns Hopkins Medicine) Working with human brain tissue samples and genetically engineered mice, Johns Hopkins Medicine researchers together with colleagues at the National Institutes of Health, the University of California San Diego Shiley-Marcos Alzheimer’s Disease Research Center, Columbia University, and the Institute for Basic Research in Staten Island say that consequences of low levels of the protein NPTX2 in the brains of people with Alzheimer’s disease (AD) may change the pattern of neural activity in ways that lead to the learning and memory loss that are hallmarks of the disease.

This discovery, described online in the April 25 edition of eLife, will lead to important research and may one day help experts develop new and better therapies for Alzheimer’s and other forms of cognitive decline.

AD currently affects more than five million Americans.

Clumps of proteins called amyloid plaques, long seen in the brains of people with AD, are often blamed for the mental decline associated with the disease. But autopsies and brain imaging studies reveal that people can have high levels of amyloid without displaying symptoms of AD, calling into question a direct link between amyloid and dementia.

This new study shows that when the protein NPTX2 is “turned down” at the same time that amyloid is accumulating in the brain, circuit adaptations that are essential for neurons to “speak in unison” are disrupted, resulting in a failure of memory.

“These findings represent something extraordinarily interesting about how cognition fails in human Alzheimer’s disease,” says Paul Worley, M.D., a neuroscientist at the Johns Hopkins University School of Medicine and the paper’s senior author.

“The key point here is that it’s the combination of amyloid and low NPTX2 that leads to cognitive failure.”

Since the 1990s, Worley’s group has been studying a set of genes known as “immediate early genes,” so called because they’re activated almost instantly in brain cells when people and other animals have an experience that results in a new memory.

The gene NPTX2 is one of these immediate early genes that gets activated and makes a protein that neurons use to strengthen “circuits” in the brain.

“Those connections are essential for the brain to establish synchronized groups of ‘circuits’ in response to experiences,” says Worley, who is also a member of the Institute for Basic Biomedical Sciences.

“Without them, neuronal activation cannot be effectively synchronized and the brain cannot process information.”

Worley says he was intrigued by previous studies indicating altered patterns of activity in brains of individuals with Alzheimer’s. Worley’s group wondered whether altered activity was linked to changes in immediate early gene function.

To get answers, the researchers first turned to a library of 144 archived human brain tissue samples to measure levels of the protein encoded by the NPTX2 gene. NPTX2 protein levels, they discovered, were reduced by as much as 90 percent in brain samples from people with AD compared with age-matched brain samples without AD. By contrast, people with amyloid plaques who had never shown signs of AD had normal levels of NPTX2. This was an initial suggestion of a link between NPTX2 and cognition.

Prior studies had shown NPTX2 to play an essential role for developmental brain wiring and for resistance to experimental epilepsy. To study how lower-than-normal levels of NPTX2 might be related to the cognitive dysfunction of AD, Worley and his collaborators examined mice bred without the rodent equivalent of the NPTX2 gene.

Tests showed that a lack of NPTX2 alone wasn’t enough to affect cell function as tested in brain slices. But then the researchers added to mice a gene that increases amyloid generation in their brain. In brain slices from mice with both amyloid and no NPTX2, fast-spiking interneurons could not control brain “rhythms” important for making new memories. Moreover, a glutamate receptor that is normally expressed in interneurons and essential for interneuron function was down-regulated as a consequence of amyloid and NPTX2 deletion in mouse and similarly reduced in human AD brain.

Worley says that results suggest that the increased activity seen in the brains of AD patients is due to low NPTX2, combined with amyloid plaques, with consequent disruption of interneuron function. And if the effect of NPTX2 and amyloid is synergistic — one depending on the other for the effect — it would explain why not all people with high levels of brain amyloid show signs of AD.

The team then examined NPTX2 protein in the cerebrospinal fluid (CSF) of 60 living AD patients and 72 people without AD. Lower scores of memory and cognition on standard AD tests, they found, were associated with lower levels of NPTX2 in the CSF. Moreover, NPTX2 correlated with measures of the size of the hippocampus, a brain region essential for memory that shrinks in AD.

In this patient population, NPTX2 levels were more closely correlated with cognitive performance than current best biomarkers  — including tau, a biomarker of neurodegenerative diseases, and a biomarker known as A-beta-42, which has long been associated with AD. Overall, NPTX2 levels in the CSF of AD patients were 36 to 70 percent lower than in people without AD.

“Perhaps the most important aspect of the discovery is that NPTX2 reduction appears to be independent of the mechanism that generates amyloid plaques. This means that NPTX2 represents a new mechanism, which is strongly founded in basic science research, and that has not previously been studied in animal models or in the context of human disease.  This creates many new opportunities,” says Worley.

“One immediate application may be to determine whether measures of NPTX2 can be helpful as a way of sorting patients and identifying a subset that are most responsive to emerging therapies.” Worley says. For instance, drugs that disrupt amyloid may be more effective in patients with relatively high NPTX2. His group is now providing reagents to companies to assess development of a commercial test that measures NPTX2 levels.

More work is needed, Worley adds, to understand why NPTX2 levels become low in AD and how that process could be prevented or slowed.

Funding for the studies described in the eLife article was provided by the National Institutes of Health under grant numbers MH100024, R35 NS-097966, P50 AG005146, and AG05131, Alzheimer’s Disease Discovery Foundation and Lumind.


© The Johns Hopkins University, The Johns Hopkins Hospital, and Johns Hopkins Health System. All rights reserved.


Physical Activity: A Viable Way to Reduce the Risks of Mild Cognitive Impairment, Alzheimer’s Disease, and Vascular Dementia in Older Adults

Brain Sci. 2017 Feb 20;7(2). pii: E22. doi: 10.3390/brainsci7020022.

Physical Activity: A Viable Way to Reduce the Risks of Mild Cognitive Impairment, Alzheimer’s Disease, and Vascular Dementia in Older Adults.

Gallaway PJ1, Miyake H2, Buchowski MS3, Shimada M4, Yoshitake Y5, Kim AS6, Hongu N7.


A recent alarming rise of neurodegenerative diseases in the developed world is one of the major medical issues affecting older adults. In this review, we provide information about the associations of physical activity (PA) with major age-related neurodegenerative diseases and syndromes, including Alzheimer’s disease, vascular dementia, and mild cognitive impairment. We also provide evidence of PA’s role in reducing the risks of these diseases and helping to improve cognitive outcomes in older adults. Finally, we describe some potential mechanisms by which this protective effect occurs, providing guidelines for future research.

1. Introduction

The alarming rise of neurodegenerative diseases in the developed world is becoming one of the major medical issues affecting older Americans. By the year 2030, >20% of Americans will be over 65 years of age [1,2]. There are now an estimated 5.4 million Americans (one in nine), aged 65 years and older, with Alzheimer’s disease (AD), the most common form of dementia, and this number is expected to almost triple by 2050, as the population ages [3]. AD has become the sixth leading cause of death in the U.S., and the fifth leading cause of death among Americans aged 65 years and older, with deaths due to AD increasing by 66% between 2000 and 2008; in contrast to the decline of most other leading causes of death during the same period [4]. AD will likely become a more prominent health issue in developing countries in the near future, as life expectancies of those populations are longer, due to improved medical care. The World Health Organization (WHO) estimates that 47.5 million people are living with dementia and 7.7 million new diagnoses are made every year, worldwide [5]. Psychological disorders, such as depression, are also common, and are the second leading cause of disability in older populations [6]. The Italian Longitudinal Study on Aging (ILSA) provided evidence in a prospective, cohort study, that depression and physical disability in older adults have a complex relationship [7]. Perhaps the most alarming aspect of the increase in dementia cases, is that there are currently no cures or new effective therapies [8]. However, some lifestyle factors, such as physical activity (PA), could lower the risk of certain forms of dementia [9]. In a recent Lancet Series on PA, Progress and Challenges (2016), Sallis and colleagues reported that regular PA could prevent almost 300,000 cases of dementia per year, worldwide, if everyone were physically active [10]. In this article, our goal is to explore the role of PA in reducing the risks of age-related AD, vascular dementia (VaD), and mild cognitive impairment (MCI). We define dementia, AD, VaD, and MCI and describe clinical and research-based assessment tools used to diagnose each disorder. Finally, we provide evidence of PA’s protective effects of cognition in older adults, and discuss some of the potential mechanisms of the protective effects of PA, proposing suggestions to guide future research on PA intervention programs in order to reduce the burden of dementia, primarily through prevention and improved health care. This review was based on searches of the US National Library of Medicine (PubMed), Ovid MEDLINE, Google Scholar, and Web of Science, using terms to identify the risk exposure (physical inactivity or sedentary), combined with terms to determine the outcomes of interest (cognitive impairment or decline or disorders or AD or dementia or MCI or VaD). A search filter was developed to include only human studies.

2. Defining and Diagnosing MCI, Dementia, AD, and VaD

2.1. Mild Cognitive Impairment (MCI)

MCI is usually described as a transitional state between normal aging and dementia [11,12]. An individual with MCI experiences a cognitive decline that is not severe enough to significantly interfere with daily life, yet is worse than expected for one’s particular age [11]. Although studies on the MCI reversion to normality and MCI stability are limited, it is common for individuals with MCI to have no further deterioration of cognitive function for several years [13,14]. In a clinical setting, physicians may diagnose MCI based on self-reported symptoms or cognitive tests, but a wide variety of operational definitions of MCI have resulted in unreliability, although progress toward an objective standard continues to be made [15]. Cognitive tests, such as the mini-mental state examination (MMSE) [16] and the Montreal Cognitive Assessment (MoCA) [17], have been developed to help screen for MCI and/or dementia. Point scores in the MMSE range from zero (severe dementia) to 30 (lack of cognitive impairment) [16]. The MMSE provides a measurement of the overall cognitive functioning, including attention and orientation, memory, registration, recall, calculation, language, and the ability to draw, to health professionals and researchers, but does not give clinicians the ability to predict if those with MCI will experience further cognitive decline due to dementia [18,19]. The MoCA was specifically developed to assist with MCI diagnosis. In a validation study, it detected 90% of MCI cases with previously established criteria for MCI, a standardized mental status test, and subjective complaints about memory loss by participants or families, over at least six months. The MoCA significantly outperformed the MMSE, which detected only 18% of the MCI cases [17]. In addition, the MoCA has been shown to be a sensitive tool for cognitive impairment associated with other clinical conditions, such as Parkinson’s disease [20], Huntington’s disease [21], and multiple sclerosis [22]. Although progress has been made toward making the MCI diagnosis objective, the concept of MCI still remains somewhat vague and controversial, and issues such as clinical criteria for practitioners need to be investigated [23]. Since MCI is a syndrome with multiple etiologies, it is not considered a disease, but an aggregate of cognitive symptoms, attributable to either an underlying precursory stage of a serious disease, or an idiopathic acceleration of cognitive decline, when compared to a normal state [19]. To signify this distinction, MCI due to AD is typically separated as the prodromal stage of AD, and it is diagnosed using criteria specific to the early stages of AD, including specific biomarkers that are not evident in other causes of MCI [24]. Although MCI sometimes persists as only a minor annoyance if it is of the non-AD variety, more often than not, it progresses to AD or another form of dementia [25]. MCI has become an important risk factor and indicator of the early stages of dementia, that has resulted in the testing of medications meant for AD treatment [26]. With MCI serving as a link between dementia and normal aging [27], it can potentially help us investigate the effect of, not only medications, but also lifestyle programs, such as regular PA, social activity, and diet, on age-related cognitive decline and dementia—both for improving cognition and delaying cognitive decline [28,29,30].

2.2. Dementia

Dementia is not a specific disease, but rather it refers to the symptomatic outcome of a number of serious neurodegenerative diseases that adversely affect cognitive function. Worldwide prevalence of people with dementia is estimated at 47.5 million, and is expected to double by 2030 and triple by 2050 [5]. Most patients with dementia display behavioral and psychological symptoms [31], such as memory loss and difficulty organizing or planning, and psychological changes, such as personality changes (aggression—verbal/physical), agitation, anxiety, depression, social withdrawal, and hallucinations [32]. Dementia is the result of serious neurodegeneration in the brain, significantly hinders daily activities, and can require a complete reliance on caregivers in later stages [32]. The most common form of dementia is AD, which causes 50%–75% of all dementia cases [33]. VaD is the second most common primary cause of dementia—at least 20% of dementia cases are due to VaD, and it is often present alongside AD or another form of dementia [34]. Although a definitive percentage is not available, due to many cases of dementia going undiagnosed, AD and VaD are estimated to be responsible for 70%–95% of dementia cases. Dementia is typically diagnosed by a healthcare provider in a clinical setting, by determining the extent of cognitive impairment, although this can be a difficult task due to dementia’s progressive nature—there is a range of severity in symptoms, depending on how far the disease has progressed when the patient is examined, and this largely relies on the examining physician’s discretion [35]. Positron emission tomography (PET) and single photon emission computed tomography (SPECT) are both brain imaging methods that are most commonly used to make a dementia diagnosis by examining the physical condition of the brain [36]. However, even with these tools, the difficulties of recognizing and diagnosing dementia are apparent, and approximately half of dementia cases are currently undiagnosed [37]. The distinctions between regular aging and the first signs of dementia may be difficult for a clinician to distinguish, and PET and SPECT scans may be expensive, which could discourage widespread testing. The changes may also happen slowly and subtly, and may thus be indiscernible to family members or caretakers. Currently, there is no cure for dementia.

2.3. Alzheimer’s Disease

Alzheimer’s disease (AD) has dramatically risen in the last couple of decades, becoming the sixth leading cause of death in the U.S., and the fifth leading cause of death among older adults, with deaths due to AD increasing by an astounding 66% between 2000 and 2008, in sharp contrast to the general decline of most other leading causes of death during the same period of time [38]. Alzheimer’s disease is a neurodegenerative, dementia-causing disease, with no known cure. Around 70% of AD cases occur after the age of 65 [39]. Amyloid-beta (Aβ) is a polypeptide—a chain of amino acids that is a protein precursor—that can build up on brain cells, causing plaques that are found in abundance in AD patients; these Aβ plaques are thought to be one of the major contributors to dementia caused by AD [40]. In addition to plaques, AD also appears to be related to tangles in the brain, which are structural abnormalities due to defective or deficient tau proteins; tau proteins support microtubules, which help provide cell structure and movement. AD is typically diagnosed by biomarkers, such as Aβ in cerebrospinal fluid, tau proteins, and regional brain volumes; these measurable substances can be used to predict AD progression in patients with MCI. However, cognitive markers, such as the symptoms reported by an examining physician, appear to be more effective predictors of the future development of AD, especially at baseline MCI, when it is first noticed and diagnosed [41]. To recognize the asymptomatic pre-clinical stage (up to a decade before the clinical onset of AD), standardized criteria for preclinical [42] and prodromal (amnestic MCI) stages [43] of the diagnostic criteria for AD, have been recommended for both clinical and research purposes.

2.4. Vascular Dementia

Vascular dementia (VaD) is the second most common form of dementia after AD, and is the result of impaired blood supply to the brain, which damages brain tissue when oxygen and nutrients are cut off. There are a number of possible causes of VaD [44]. It is often the result of a number of small, focal cerebral infarcts (small strokes) that may go unnoticed individually, but have an additive detrimental effect as more and more small areas of the brain are destroyed by ischemic events; however, there are also a number of other causal subtypes of cerebrovascular disease [45]. VaD may also be present along with other forms of dementia, such as AD, which can further complicate the condition, aggravating dementia symptoms, as access to more areas of the brain are lost. Diagnosing VaD is therefore no simple matter; there is currently a lack of validated criteria for establishing a diagnosis, and many of the various pathologies that reduce the brain’s blood supply are complex [46]. Although cerebrovascular lesions can be seen using brain imaging techniques, the diagnosis of VaD remains difficult, since such lesions may or may not be contributing to dementia symptoms, and this can lead to over-diagnosis of VaD as the cause of dementia [47].

2.5. Progression of a Neurodegenerative Disorder

Age-related neurodegenerative disorders, such as AD and VaD, generally show the same patterns in their progressions from normal aging to dementia. First, symptoms of MCI develop. MCI symptoms may improve if the condition is transient, and the patient may even go back to experiencing normal aging. The subject may also experience and remain in the MCI stage, without the condition progressing to dementia [13,14,25,26,27]. However, if there is an underlying cause, such as AD or VaD, MCI will eventually progress to dementia, and this step is irreversible. Intervention before irreversible brain damage occurs, is the best clinical practice for reducing the impact of dementia [28,29,30].

Numerous studies have revealed the connections between frailty, a pathological aging process that is reversible [48], and neurodegenerative disorders [49]. Cognitive frailty was first proposed by Panza and colleagues, who reported the risks of decreased cognitive functions, modulated by vascular factors [50]. In 2013, the International Academy on Nutrition and Aging and the International Association of Gerontology and Geriatrics, defined cognitive frailty as the heterogeneous clinical syndrome condition in older adults with both physical frailty and cognitive impairment, but excluding those with AD and other dementias [51]. Cognitive frailty is further refined into two subtypes; reversible and potentially reversible cognitive frailty [52]. The cognitive impairment of reversible cognitive frailty is subjective cognitive decline (SCD), a type of cognitive decline that may appear as the first symptom of preclinical AD, and/or positive biomarkers resulting from physical factors. [52]. MCI is the cognitive impairment of potentially reversible cognitive frailty. Recently, a longitudinal population-based study reported that reversible cognitive frailty in older adults increased the risk of developing dementia, particularly VaD, but not AD, and all-cause mortality [53]. The authors suggested that older adults with reversible cognitive frailty could benefit from a cognitive impairment intervention that may include regular PA, diet (e.g., Mediterranean diet), smoking cessation, and an active social lifestyle [53]. More research is required to determine the clinical screening criterion of cognitive frailty and the effectiveness of interventions for individuals with other geriatric disorders.

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3. Risk Factors for AD, VaD, and MCI

There are a number of risk factors for AD, the most obvious of which is advanced age. In addition to environmental factors, genetic causes are implicated, as several genes that have been associated with AD; the most undisputed and well-known of which is the gene that encodes apolipoprotein E (APOE). The APOE gene is the strongest genetic risk factor for the development of late-onset AD, which accounts for >95% of all AD cases [54,55,56]. Many epidemiological studies suggest that the APOE ε4 allele carrier status of individuals have associations between modifiable lifestyle risk factors, and dementia and AD [57,58,59,60]. Accumulating data suggest the APOE ε4 allele plays an important role in Aβ plaques and clearance, tau protein tangle formations, oxidation, neurotoxicity, and dysfunction in lipid transport, which are the major hypotheses of AD pathogenesis [61]. The epidemiological population-based study which had an average of 21 years of follow-up times before the diagnosis of dementia, showed that APOE ε4 allele carriers’ risk of dementia may be more affected by lifestyle factors such as PA, dietary fat and fish oil intake, alcohol drinking, and smoking. The authors suggested that adopting a healthy lifestyle, including increased PA, should be utilized as a major preventive strategy to decrease the risk or postpone the onset of dementia among APOE ε4 allele carriers [62]. The genetics of AD is advancing quickly, as new AD-related genes continue to be found [63]. However, to date, no therapeutic interventions targeting the APOE or other genes have been successfully established [64,65].

Cardiovascular disease (CVD) is another apparent risk factor for AD, particularly peripheral arterial disease—a form of atherosclerosis [66,67]. According to a number of studies, depression in later life also presents a significant risk for acquiring AD [68,69]. Within a three-year period, depressed MCI patients had a twofold higher risk of developing AD than non-depressed MCI patients [70]. Hypertension [71], diabetes [72], hypotension [73], and hypercholesterolemia [74], are all additional risk factors for AD [75,76]. Poor sleep quality and sleep deficiency may present yet another risk factor, as sleep deprivation induces more Aβ buildup in the brain, while adequate sleep reduces it—moreover, Aβ buildup may also cause poor sleep patterns and increased wakefulness [77]. Poor sleeping patterns may therefore lead to increased Aβ formation, to further deteriorate sleep quality, resulting in positive feedback that may increase AD risk. There are a number of risk factors for VaD that are also risk factors for AD, including hypertension, diabetes, excessive adiposity, and dyslipidemia [78]. Although the effect of these conditions on VaD may be obvious due to their cardiovascular or metabolic nature, the link to AD may be more indirect, as the resultant disruption of vascular functions in the brain could be compounding the neurodegeneration caused by the Aβ plaques or neurofibrillary tangles of AD, by disrupting cerebral autoregulation [75,76,79]. The risk factors for MCI are generally the same as those for AD—this is to be expected because MCI can also be the prodromal stage of AD. The most significant risk factors for MCI are older age and hypertension [80]. Now that we have addressed the potential risk factors for the most common age-related neurodegenerative diseases, we can explore the role of PA as a protective or risk-reducing behavior.

4. Physical Activity’s Effect on Future Risk of MCI, Dementia, AD, and VaD

PA is beneficial for both physical fitness (e.g., changes in the cardiovascular system, bone and muscle) and mental health (e.g., emotional functioning—depression, moods, cognitive functioning, social functioning) in almost all older adults [9,81], and its effects have been extensively studied in healthy older adults and those with cognitive impairment, including MCI, dementia, AD, and VaD.

4.1. Long-Term Cognitive Effects of PA on Healthy Older Adults

PA throughout one’s life can enhance cognitive function later in life, so it should be encouraged at every age. In contrast, sedentary behaviors, such as viewing television for extended periods over the course of years, can negatively affect cognitive function later in life. A longitudinal study over 25 years, that measured the PA and television viewing habits of 3247 healthy adults (aged 18–30 years at the start of the study), found that higher levels of PA and lower amounts of television viewing, resulted in significantly better processing speeds and executive functions in cognitive tests at midlife [82]. Moreover, those who were physically active in midlife had a reduced risk of developing depression in late life [83]. Depression in late life has also been linked to dementia, particularly in those carrying the ε4 variant of the APOE gene that predisposes to AD in depressed individuals [84]. According to the findings of a 10-year longitudinal study involving 470 participants aged 79–98 years, PA can also help engage older adults in cognitive and social activities, which may be one of the factors that helps prevent cognitive decline [85]. Ideally, all adults should remain physically active throughout life [10,86], starting at a young age, to achieve optimal cognitive health as an older adult. However, there may be shorter-term benefits to increased PA levels [87,88,89,90].

4.2. Short-Term Cognitive Effects of PA on Healthy Older Adults

For healthy older adults, the short-term effects of PA need further investigation. One study found that the cognitive functions of memory and independence were improved in older adults (aged > 75) by a single session of low-intensity, range-of-motion exercise, but the effect might also be short-lived [87]. Another study found that healthy older adults practicing Tai Chi, or simple stretching and toning exercises, can improve global cognitive function, improve recall, and reduce subjective cognitive complaints after a one-year intervention [88]. Certain exercises, such as range-of-motion and Tai Chi, may show short-term benefits in cognitive ability in healthy older adults [87,88]. Aerobic exercise has been shown to attenuate cognitive decline, reduce brain atrophy, and improve physical health in healthy older adults [89,90], although there is some evidence that short-term cognitive effects are not as pronounced [89]. A review of 12 trials lasting from eight to 26 weeks, and included 754 older adults with no cognitive impairment, showed no short-term cognitive benefits from aerobic exercise [89]. However, the age of the older adult may also factor into the efficacy of aerobic exercise. One study showed that adults between 60 and 70 years old displayed significant cognitive benefits in spatial object recall and recognition from a three-month aerobic PA intervention that increased hippocampal perfusion—blood flow to the hippocampus. However, the positive effect of aerobic PA on perfusion may decline with age [91].

In recent years, there has been growing interest in resistance training (e.g., weight lifting, strength training) to improve cognition [92,93,94,95] and prevent brain volume loss in older adults [96]. The long-term impact on cognition and white matter volume in older women was reported in a 52-week randomized clinical trial of resistance training program that included machine exercises Keiser pressurized air system, free weights, non-machine exercises, or balance-and-toning training program that included stretching, range-of-motion, core-strength, balance, and relaxation exercises. Both interventions were performed twice per week. The resistance training program promoted memory, reduced cortical white matter atrophy, and increased peak muscle power after 2-year follow-up, relative to the balance-and-toning training program [96]. Also, it has been reported that cortical white matter volume is reduced among older adults with dementia, when compared to their healthy counterparts [97]. Thus, maintaining cortical white matter volume might be important for maintaining cognitive functions in older adults [96].

There are several studies supporting the hypothesis that resistance training has similar positive effects on cognitive function among older adults, to aerobic-based exercise training. However, there is no clear consensus on the underlying mechanisms by which resistance training promotes cognitive function and brain tissue integrity [9,95,96]. More research is needed to examine the variables of resistance training (i.e., intensity, frequency) and the possible mechanisms by which resistance training may prevent cognitive decline. A recent meta-analysis found that combined aerobic exercise and resistance training, had greater effects on reducing cognitive decline than these programs alone [98]. Current understanding of how PA promotes cognitive function is largely from aerobic training studies. Further research is required to identify the underlying changes in the body and brain (e.g., changes in brain volume) that improve cognitive function, using neuroimaging, physiological assessment, and circulating levels of various neurotrophins (e.g., IGF-1). Subsequent research should also determine how and what types of PA could help both healthy and frail older adults gain cognitive benefits in social and environmental settings of daily life.

4.3. Effects of PA on the Risk of Developing MCI and Dementia in Older Adults

PA is effective in reducing risk for developing MCI in older adults, but the optimizing of exercise training (i.e., types of PA, intensity, duration), cardiorespiratory fitness, age, level of cognition, medications, and social environments, may all play roles in the outcome [9]. The studies mentioned above showed that stretching and toning exercises hold the most promise for improving cognitive function in the healthy adults aged 75 years and older [87,88], while aerobic [90,91,99] and resistance exercise [92,93,94,95] also have positive effects. It seems that the risk of developing MCI may also be improved by exercise intensity. In older adults (aged ≥ 65 years), moderate exercise was shown to reduce the risk for MCI, while vigorous or light exercise did not show similar effect [100]. Increased PA in older adults also appears to reduce the risk of dementia due to AD and VaD, although more research must be done to explore the mechanisms of this effect [90,95,96]. In one study, adults of 65 years and older, participating in the Cardiovascular Health Cognition Study who regularly participated in four or more physical activities per week, had about half the risk of developing dementia as those participating in zero to one physical activities. However, those carrying the ε4 variant of the APOE gene—the greatest genetic risk factor for late onset AD—the risk was not affected by PA levels [101]. The frequency of the APOE ε4 gene is 19.0% in African American, 13.6% in Caucasian, 11.0% in Hispanic, and 8.9% in Japanese populations [102]. As mentioned earlier, for the majority of the population—those without the APOE ε4 gene—PA may have protective effects against the development of dementia [62]. This finding is supported by other studies showing a significant reduction of dementia found in older adults who exercised three or more times per week, when compared to those who did not [103]. Nevertheless, the mechanisms by which different types and frequencies of PA reduce dementia risk in older adults warrant further research.

4.4. Effects of PA on Older Adults with Cognitive Impairment

For older adults who have already developed a form of cognitive impairment, whether mild, such as those with MCI, or moderate to severe, as with dementia, PA can improve cognitive function, when compared to those with cognitive impairment who are not physically active [104]. Studies show that six to 12 months of exercise for those with MCI or dementia results in better cognitive scores than sedentary controls [105]. The positive effect of PA on cognitive function may be more apparent in older adults with MCI than in those with dementia, according to one review, but this may be due to the methodological issues of the performed studies; thus, more research is needed on the effect of PA on cognitive function in older adults with dementia [105]. However, the meta-analysis showed that aerobic exercise helps improve cognition in older adults with both AD and non-AD dementia, when combined with other standard medical treatments for dementia, and higher frequency interventions did not result in additional effects on cognition [106]. The results offer supporting evidence that PA intervention, with or without pharmacotherapy, is beneficial for cognition in patients with dementia.

5. Potential Mechanisms for PA’s Protective Effects

While the protective effect of PA on the aging brain is supported by numerous studies, the exact mechanisms are less clear. A recent review examined many possible mechanisms for how PA is linked to a reduced risk of age-related cognitive impairments, including MCI, AD, and VaD [107]. In this section, we will examine some of these potential mechanisms.

5.1. Increasing Blood Flow to the Brain

PA can increase blood flow to the brain, both during and shortly after a PA event, in response to increased needs for oxygen and energetic substrate [108,109]. The increased brain/cerebral blood flow triggers various neurobiological reactions, which provide an increased supply of nutrients. Moreover, cerebral angiogenesis—the development of new blood vessels in the brain—is increased by PA, and the brain’s vascular system is plastic, even in old age [110]. The increased vascularization of the brain, as well as the regular increases in blood flow that periods of PA provide, may reduce the risks of MCI and AD, by nourishing more brain cells and helping to remove metabolic waste or AD-inducing Aβ. The potential risk-reducing effect of increased blood flow on the development of VaD is more obvious, since VaD involves an impaired blood supply to the brain, while PA increases the blood supply. For instance, if a small artery in the brain is occluded by an embolus, this can often lead to an ischemic stroke, but blood can sometimes reach affected brain cells from an alternative path. Increased vascularization in the brain from PA can increase these alternative sources of blood during arterials occlusions, possibly limiting the damage [111]. There is strong evidence that cerebrovascular health may also play a large role in the severity of AD, as cases with brain infarctions, in addition to AD, showed worse symptoms of dementia than those with only AD [112]. More research is needed to determine the extent to which increasing vascularization of the brain may help reduce the risk of age-related neurodegenerative diseases.

5.2. Improving Cardiovascular and Metabolic Health

Earlier, we discussed how hypertension is one of the main risk factors for MCI, AD, and VaD [71,79]. Hypertension can increase the risk of strokes, as well as small strokes that are often the cause of VaD. Since strokes can complicate AD and aggravate dementia symptoms, it follows that hypertensive individuals could benefit by lowering their blood pressure, regardless of their level of cognitive impairment. Even low-intensity PA for 30 min, three to six times a week for nine months, can significantly lower blood pressure in elderly adults [112]. Because hypertension is a prominent risk factor, lowering blood pressure may be one of the mechanisms by which PA reduces the risk of many age-related neurodegenerative diseases. Diabetes is also a very significant risk factor for MCI, AD, and VaD [72]. The excess blood glucose levels found in those with diabetes causes tissue damage [113], inflammation [114], and microvascular disease [115], which possibly affect brain tissue, consequently increasing the chance of stroke. Regular PA can prevent type 2 diabetes and also helps manage blood glucose levels in those with diabetes [116]. By reducing the risk of diabetes and improving health conditions, improvement of metabolic health may be a secondary mechanism by which PA decreases the chances of MCI, AD, and VaD. Another risk factor for cognitive impairment in older adults that we have previously discussed is hyperlipidemia, or abnormally high lipid (cholesterol and triglycerides) blood concentration [74,78]. Regular PA can increase blood level high-density lipoproteins (HDL) that help carry cholesterol out of the bloodstream and into the liver, reducing hyperlipidemia. Thus, it seems plausible that PA reduces neurodegeneration risk through general cardiovascular and metabolic health improvement [117].

5.3. Preventing and Treating Depression

Depression is a known risk factor for developing dementia. Depression also appears to reduce certain cognitive functions in adults who are otherwise not cognitively impaired [118]. Although midlife depression doubles the chances of acquiring dementia later in life, it is harder to distinguish whether late-life depression is a risk factor for dementia, or vice versa; it could be a result of the early stages of dementia or MCI [119]. PA is effective for both treating and preventing depression [120], and therefore, it would stand to reason that reducing depression could be one of the means by which PA reduces the risk of AD, MCI, and other cognitive disorders. Even in cases where late-life depression is caused by the early dementia symptoms, PA could still be encouraged as part of a treatment for the depressive symptoms. Future research is needed to determine how health care professionals can deliver a PA program to healthy or physically/cognitively frail older adults. There is a need to determine the external factors of PA intervention, such as timing, dose, type, structure, and use of mindfulness that best ameliorate depression, and thereby reduce the risk of cognitive decline and prevent dementia.

5.4. Improving Sleep Quality

PA is associated with a reduction of insomnia symptoms, and other sleep quality and quantity problems, including problems with sleep onset (being able to fall asleep quickly) and sleep maintenance (staying asleep throughout the night) in older adults [121]. We previously noted a study showing that poor sleep quality is a potential risk factor for AD in particular [61], as sleep disturbances occur frequently in older adults with dementia [122] A specific mechanism by which sleep may reduce the risk of AD is through metabolic waste clearance in the brain, that occurs during sleep; this process also clears Aβ from the brain [123]. Aβ buildup results in plaques that contribute to AD, so clearing it from the brain during the deep stages of sleep may be the reason why adequate sleep reduces the risk of developing AD. This may also be a potential mechanism of the protective effect of PA on brain health in older age; PA promotes better sleep quality, which may in turn, helps clear harmful wastes, such as Aβ from the brain, thereby reducing the risk of dementia.

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6. Conclusions

Several studies demonstrate the protective effect of PA on brain health, particularly by reducing the risk for the neurodegenerative dementia-causing diseases, AD and VaD, as well as their precursor, MCI. We have described potential direct and indirect mechanisms of this protective effect. More research is warranted to explore the relationships between PA and the aging brain. Other factors, including genetics, may affect the development of neurological disorders. However, in most cases, moderate PA is beneficial for both physical and mental health in older adults. Moderate-intensity aerobic exercise, resistance training, stretching, toning, and a range of motion exercises, may yield cognitive benefits in older adults. Although the exact mechanisms by which PA decreases the risk for dementia is not fully understood, PA should be encouraged [124], since it improves the quality of life for all older adults. The existing evidence shows that rates of dementia could be reduced, if people were physically active [10]. There is a possibility that PA may become the most important behavioral factor in facilitating healthy mental and physical aging (Figure 1). Current evidence supports PA’s short and long term cognitive benefits, regardless of age. Many mechanisms responsible for the PA’s protective effect against age-related cognitive impairment are still not fully understood.



Diet Drinks Linked to Increased Stroke and Dementia Risk

( New question marks over the safety of diet soda have arisen following a study linking intake of artificially sweetened beverages to both stroke and dementia.

The study, published online in Stroke on April 20, showed that consumption of one can of diet soda or more each day was associated with a three times increased risk for stroke and dementia over a 10-year follow-up period compared with individuals who drank no artificially sweetened beverages.

“There are many studies now suggesting detrimental effects of sugary beverages, but I think we also need to consider the possibility that diet drinks may not be healthy alternatives,” lead author, Matthew P. Pase, PhD, Boston University School of Medicine, Massachusetts, told Medscape Medical News.

“We can’t show cause and effect in this study as it is observational in design, but given the popularity of diet drinks we desperately need more research on this question.”

He is not yet recommending against diet beverages based on this study, he added,

“but I would urge caution — especially to those individuals who consume multiple diet drinks daily. I believe we need to rethink the place of these drinks.”

It is possible that the observation could be due to reverse causality, he noted.

“It is not clear whether the diet sodas are causing stroke and dementia or whether unhealthy people gravitate more towards these drinks than healthier people.

“If you already have cardiovascular risk factors, you are likely to have been advised to lower your sugar intake and so may move away from sugary beverages to diet drinks,” Dr Pase said.

“We did find that a higher intake of diet soda was linked to diabetes at baseline, but again we don’t know which came first. Did the diet drinks increase the risk of developing diabetes, or did diabetic patients choose diet drinks as they have to limit their sugar intake?”

The link between diet drinks and dementia became nonsignificant when adjusted for vascular risk factors. Dr Pase suggested this could be because the association may be mediated through vascular risk factors — artificial sweeteners could be increasing vascular risk factors.

“Or it could just be that people with vascular risk factors drink more diet sodas, which is perfectly possible as they could have been advised to cut down on sugar.”

The link with ischemic stroke was still there in all models after adjustment for all other risk factors.

Sugar-sweetened beverages were not associated with stroke or dementia risk, but the authors say this should not be taken as evidence that sugary drinks are safe.

“There are many other studies suggesting harmful effects of sugar-sweetened drinks, and we did not have large enough numbers of people consuming sugary drinks in our current study for reliable information on this,” Dr Pase said.

“We had much larger numbers of individuals reporting intake of artificially sweetened drinks.”

Another study by the same group, published online in Alzheimer’s and Dementia on March 5, shows a link between consumption of both sugar-sweetened and artificially sweetened beverages and reduction in brain volume in a middle-aged cohort. In the cross-sectional study, the sugary drinks, which included both soda and fruit juice, were also associated with worse episodic memory.

“Greater intake of total sugary beverages, fruit juice, and soft drinks were all associated with characteristics of preclinical Alzheimer’s disease,” the authors concluded.

“Additional studies are warranted to confirm our findings and evaluate if sugary beverages are associated longitudinally with worsening of subclinical Alzheimer’s disease and with incident Alzheimer’s disease.”

Commenting on these studies for Medscape Medical News, Keith Fargo, PhD, director of scientific programs and outreach at the Alzheimer’s Association, said,

“Both studies are difficult to interpret — the conclusions are a bit different to one another — but epidemiological data is messy.”

Still, he added, “These two papers should certainly sound warning bells, but neither are suggesting we can take just one simple step of cutting out sodas and or juice to reduce our risk of stroke or dementia. We must look at the whole picture of diet and exercise, of which this is just one very small piece.”

“Of the two papers, it is easier to grasp that high sugar intake is not doing good things to the brain, but there is growing evidence in the literature that diet drinks are not necessarily the panacea that some once might have believed them to be,” Dr Fargo noted.

“We can’t say from this data that that someone who drinks a few diet [beverages] will have a significantly higher risk of dementia. It’s all just speculation. The best thing we can do is conduct further studies to find out more. The health recommendations are unlikely to be simple, but perhaps it may not be the best idea to replace a sugary beverage with an artificially sweetened drink. It’s a better idea to skip both and just drink water.”

In the study published in Stroke, researchers analyzed data from the Framingham Heart Study Offspring cohort on intake of sugar sweetened and artificially sweetened beverages and the incidence of a first stroke or diagnosis of dementia.

The stroke cohort included 2888 participants older than age 45 years (average age, 62 years) and the dementia cohort included 1484 participants older than age 60 years (average age, 69 years).

All participants had completed regular food intake questionnaires. For the current study, researchers focused on beverage intake from 1991 to 2001 and the occurrence of stroke or dementia in the following 10 years.

There were 97 cases of incident stroke (82 ischemic) and 81 cases of incident dementia (63 consistent with Alzheimer’s disease).

Results showed that after adjustments for age, sex, education (for analysis of dementia), caloric intake, diet quality, physical activity, and smoking, higher recent and higher cumulative intake of artificially sweetened soft drinks were associated with an increased risk for ischemic stroke, all-cause dementia, and Alzheimer’s disease dementia.

When the researchers compared daily cumulative intake to 0 beverages per week (reference), the hazard ratios were 2.96 (95% confidence interval [CI], 1.26 – 6.97) for ischemic stroke and 2.89 (95% CI, 1.18 – 7.07) for Alzheimer’s disease.

On the diet drink results, he said, “We found that people who drank at least one can of diet soda each day had a 3 times increased risk of stroke and dementia than those not drinking any such beverages.”

He noted that lower intakes (between 1 and 6 drinks a week) were still associated with stroke but not dementia.

Sugar-sweetened beverages were not associated with stroke or dementia.

In addition to the smaller numbers on sugary beverages, there was also the possibility that more of those who drank sugar-sweetened beverages may have died of heart disease during the study period and would therefore not be included in the stroke and dementia endpoints, he said.

Dr Pase said it is not known how diet soda could be causing harm, but there some data suggest that artificial sweeteners may predispose toward weight gain.

“Animal studies have shown that rats given artificial sweeteners gain weight more than rats given an identical diet without artificial sweeteners,” he said.

“These artificial sweeteners have also been linked to a change in the composition of gut bacteria and the development of glucose intolerance. There is some data on this in humans too, but it is much more difficult in humans to show cause and effect.”

He added: “There is the possibility that the association of sweetness and calories becomes uncoupled in the brain when we consume artificial sweeteners. The brain is conditioned to expect calories when it senses a sweet taste, but if this doesn’t happen maybe people tend to overcompensate with other sweet food.”

Markers of Preclinical Alzheimer’s

In the study published in Alzheimer’s and Dementia, the researchers, again led by Dr Pase, used Framingham data to look at possible links between sugar-sweetened and artificially sweetened beverage intake and results of neuropsychological (n = 4276) and MRI (n = 3846) markers of preclinical Alzheimer’s disease.

They found that greater consumption of total sugary beverages was associated with lower total brain volume and lower memory scores. Relative to no intake, the difference in total brain volume associated with consuming 1 to 2 or more than 2 sugary beverages per day was equivalent to 1.6 and 2.0 years of brain aging, respectively, and the difference in memory scores was equivalent to 5.8 and 11.0 years of brain aging, respectively.

Higher diet soft drink intake was associated with smaller total brain volume and poorer performance on one of the neuropsychological tests.

In an editorial accompanying the study published in Stroke, and addressing the results with the diet drinks, Heike Wersching, MD, University of Munster, Germany, and Hannah Gardener, ScD, and Ralph L. Sacco, MD, University of Miami Miller School of Medicine, Florida, reiterate that whether the observed associations between artificially sweetened beverages and stroke and dementia are causal or reflect reverse causation bias is difficult to elucidate, and further studies are needed.

They suggest that future epidemiologic studies could include requirements for data on previous weight fluctuations, dieting behavior, changes in sweetened/artificially sweetened beverage consumption over time, and reasons for choosing artificially sweetened beverages.

“The work by Pase et al highly encourages further discussion and more research into this question, for even small causal effects would have tremendous effects on public health due to the popularity of both artificially sweetened and sugar sweetened beverage consumption,” they conclude.

They add that the current body of literature is inconclusive about the causal nature of the associations between artificially sweetened beverage consumption and risk for stroke, dementia, diabetes mellitus, and the metabolic syndrome.

The growing number of epidemiologic studies showing strong associations between frequent consumption of artificially sweetened beverages and vascular outcomes, however, suggests that it may not be reasonable to substitute or promote these drinks as healthier alternatives to sugary drinks.

“Both sugar-sweetened and artificially sweetened soft drinks may be hard on the brain,” they conclude.

 Stroke. Published online April 20, 2017. Abstract, Editorial

Alzheimer’s & Dementia. Published online March 5, 2017.  Abstract


By Sue Hughes

Copyright © 1994-2017 by WebMD LLC.


‘Everybody Knows Somebody’: This State is a Laboratory for the Future of Alzheimer’s in America

( North Dakota’s sparse geography has long made it a natural frontier: Pioneers here pushed the boundaries of westward expansion, then agriculture, and recently domestic oil drilling. Now the state finds itself on the leading edge of a new boom that it never would have chosen: Alzheimer’s disease.

Cases are climbing across the United States, and especially in North Dakota, which has the country’s second highest death rate from the disease. While Alzheimer’s is the sixth leading cause of death nationally, it already ranks third here.

“Everybody knows somebody” affected by the disease, said Kendra Binger, a program manager with the Alzheimer’s Association of Minnesota and North Dakota. As public awareness rises along with the numbers of cases, “it’s hard to ignore anymore.”

This makes the state an ideal laboratory to glimpse at the future of Alzheimer’s in America, and to identify strategies that could help the rest of the country cope. The devastating disease has strained families and the state budget. So North Dakota — a place that prides itself on personal independence and financial parsimony — has found new ways to support its residents and a new consensus to spend money on prevention.

The state’s primary strategy is to assist family caregivers — the estimated 30,000 North Dakota spouses, siblings, sons, and daughters looking after loved ones with dementia. A half-dozen consultants roam the state to evaluate families’ needs, train caregivers, connect them to services, and offer advice. Studies show the program has helped families keep their loved ones out of nursing homes and save the state money.

“We are not well-prepared, to put it mildly,” to respond to the growing Alzheimer’s crisis across the country, said Marc Cohen, clinical professor of gerontology and director of the Center for Long-Term Services and Supports at the University of Massachusetts, Boston. Since the burden of caring for dementia patients falls heavily on family members, he added, strategies like North Dakota’s are “exactly what is needed.”

Betty Mahlke, a retired bookkeeper, discovered the impact of North Dakota’s approach two years ago, when her husband, Larry, started forgetting everyday details — a troubling symptom of the Alzheimer’s diagnosis he’d received years before. It’s lonely enough caring for a loved one with dementia in the heart of a city, surrounded by service organizations and care options. But like Betty, many of North Dakota’s growing ranks of family caregivers are doing it in far lonelier places: on isolated farms or in small towns across 350 miles of the Great Plains.

The Mahlkes lived in Jamestown, a city of 15,000 halfway between Fargo and Bismarck, a hundred miles from each. Jamestown is hardly the state’s most remote community; it is home to the National Buffalo Museum, a stock car racetrack, and high school football games that Larry Mahlke loved to frequent. But it has limited support services compared to a big city. So when a visiting consultant, Beth Olson, came to give a presentation on dementia at the local senior center in March 2015, Betty seized the chance.

“Every little hint” about how to care for Larry resonated, Betty recalled.

“I was just grasping for anything that could help.”

Soon after, Olson visited the Mahlkes at home, and that began a relationship that would carry Betty through the deepening challenges to come. At first, Olson suggested puzzles and games that could help Larry, a retired furnace installer and insurance salesman, keep his mind active. When he later stopped recognizing his own home, she coached Betty on the best response. Instead of arguing, Betty would invite him into the car, drive a few blocks, drive back, and say they were home. Sometimes the gambit worked, Betty said.

“Other times he’d say, ‘This is not my house,’ and we’d have to drive around some more.”

Olson’s personalized support of the Mahlkes is North Dakota’s model for easing the burden of Alzheimer’s and other forms of dementia. Olson is a care consultant with the state’s Dementia Care Services Program, established in 2009. Republican state Senator Dick Dever proposed the program after discovering personally the difficulty of caring for a family member with Alzheimer’s. The state Legislature approved it with overwhelming support in both houses. Michigan is now piloting a similar program in three counties and working to expand it statewide.

What makes North Dakota such an Alzheimer’s hot spot? Like much of the rest of the Midwest, it’s graying. Rural counties are emptying out as young people depart for better job prospects elsewhere, leaving an earlier, aging generation behind. This is a familiar story for Betty Mahlke, whose four grown sons all settled out of state (in Minnesota, Nevada, and Idaho) for the sake of work.

The youth exodus has been countered in North Dakota by a flood of young arrivals coming to work the oil fields — but only in a fraction of the state’s counties, and not enough to divert the overall trend. The state still has a high ratio of elderly residents. Especially large is the group called the “oldest old,” those age 85 and over, who are dramatically more likely to die from Alzheimer’s than the group age 65 and over. In the latest US Census, only Rhode Island had a larger portion of its populace in the “oldest old” range.

Still, that explanation doesn’t satisfy Dr. Donald Jurivich, chair of geriatrics at the University of North Dakota School of Medicine and Health Sciences, who believes there’s more at play than migration patterns. When he shows his colleagues North Dakota’s high dementia numbers, he said,

“People have pretty much been stupefied.” Why wouldn’t Rhode Island, with its higher ratio of “oldest old,” match North Dakota in dementia deaths?

And why not Iowa, whose population of “oldest old” is nearly as high? The only state with a comparable ratio of the very elderly whose dementia death rate surpasses North Dakota is neighboring South Dakota.

Jurivich and his colleagues have speculated on a host of possible causes, none yet proven: Perhaps North Dakota’s high Alzheimer’s death rates could be explained by radon exposure, a meat-heavy diet, genetic predispositions among the northern Europeans who settled this part of the Midwest, or simply state-by-state differences in record keeping. He’s applying for grants to fund further study to solve the mystery.

The Dementia Care Services Program, meanwhile, has to cope with the realities on the ground. The program, run by the regional Alzheimer’s Association, substantially expanded the shoestring work that the association was doing before 2009. Previously, two consultants had covered the entire state, counseling families one-on-one (including Dever’s family) and raising their own funds. Thus stretched, they couldn’t range far beyond Fargo and Bismarck, the two largest cities.

Now, six care consultants do the job, dividing the state into eight zones. As Olson did with the Mahlkes, the consultants assess patients’ needs, teach caregivers what to expect and how to respond, refer them to services, lead support groups, and answer questions by phone and in person. Importantly, they often visit patients’ homes, even those in the remotest corners of the state. Between January 2015 and this February, nearly three-quarters of the 2,602 consultations were done in person.

Deaths from Alzheimer’s have jumped 74 percent since 2000 in North Dakota, and the program’s caseload has similarly exploded. The number of families served has risen steadily since 2011, from about 500 in every two-year period to a current pace that could double that. The program costs the state $600,000 a year.

The program’s main purpose is to help families keep loved ones with dementia at home, rather than in a nursing facility, for longer. With average nursing home costs running over $8,000 a month per patient, and the state’s share of Medicaid paying half the price, even a few weeks’ delay can make a dent. For families, having the knowledge and support to keep a loved one at home can also make a big emotional impact, relieving the bewilderment and burnout that often afflicts caregivers and preventing costly, avoidable medical care for patients and caregivers alike.

That’s what it did for Betty Mahlke. Though the caregiving exhausted her, she couldn’t stomach the idea of moving her husband into a care facility. When Larry eventually couldn’t recognize even her, Olson had already prepared her for how to respond.

“We’d be sitting in the living room and he would look at me strangely, and you could see that fear in his eyes, that this lady is not anybody he knows,” Betty recalled.

“There were times when we’d go to bed at night and he’d lay on the edge of the bed, stiff as a board.”

When Larry said, “Where’s Betty?” she knew to reassure him: “I’ll go try and find her.” Then she’d leave the room, change her shirt, and come back in.

Without that preparation, Betty said, she wouldn’t have known how to handle Larry’s confusion. And if she’d had to travel to a bigger city to attend the presentation that first introduced her to Olson, she’d never have gone. All told, without the Dementia Care Services Program, she said, she could never have kept Larry at home for so long.

A formal evaluation of the program backed up stories like Betty’s with statistics. The study, conducted at the University of North Dakota Center for Rural Health, looked at the first 3 1/2 years of the program. Caregivers reported that it helped them feel more empowered, less likely to need emergency room visits and hospitalizations for their loved ones, and less likely to place their loved ones in long-term care. The researchers estimated the resulting cost savings at $800,000 for medical and hospital services avoided and $39 million for long-term care.

Michigan, too, studied its similar, small pilot program and found that it reduced nursing home placements by more than 9 percent and saved the state over $500,000 in a single year.

The bottom line, said Brad Gibbens, deputy director of the UND Center for Rural Health:

“If you can provide some support services for the family caregiver, you can improve the lives of those with dementia and the family caregiver, and likely save the public taxpayer some money.”

Even so, the North Dakota program lost over 10 percent of its funding in a budget crunch last year and could face further cutbacks as the state grapples with a continued shortfall. This comes as Republican congressional leaders in Washington have proposed capping Medicaid money sent to states as part of the Affordable Care Act repeal, which could make such dementia care programs all the more important.

Over the past quarter-century, the balance of Medicaid money spent on long-term care has shifted away from nursing homes and toward more home- and community-based care. UMass Boston’s Cohen warns that the proposed caps could reverse that trend, resulting in cuts for optional support programs and thus sending more patients into nursing homes.

“If there is less money available to pay for home and community-based care,” he said, “families will have to pick up the slack — or people will have greater unmet need — and training to make them more effective will become more important.”

As the number of Alzheimer’s patients grows and federal dollars potentially dwindle, other states are likely to need to develop similar supports for families, for reasons both humane and pragmatic.

“We know people do better at home, and people want to care for their loved ones at home,” said Gretchen Dobervich, a one-time field director for the regional Alzheimer’s Association who now represents Fargo as a Democratic member of the state Assembly.

Plus, “with the large numbers of people we’re going to see with this disease, there’s no way we’re going to be able to have enough care facilities to treat the number of diagnoses we’re going to see.”

The North Dakota program ultimately enabled Betty Mahlke to care for Larry at home until just three weeks before his death. One day in March 2016, a year after entering the Dementia Care Services Program and six years after his initial diagnosis, Betty went out for a few hours and left Larry in the care of a health aide from a company Olson had helped her find. Larry, disoriented and distressed, shoved the unfamiliar woman and walked out of the house, searching for Betty. He walked a block in the late-winter cold without a coat or shoes on. Betty told Olson, who happened to be in town for an event, and the two of them brought him home.

The next night, his last night at home, Betty and Larry had a picnic dinner in the living room and danced waltzes like they had as younger sweethearts. The following day, Betty brought him to a nursing home, where hospice helped pay part of the staggering $1,860-per-week cost. Larry died less than three weeks later, at age 74. The Mahlkes had been married for 51 years.

“I don’t think that he suffered” during those few weeks in the nursing home, “so that was a blessing,” Betty said.

“I did it for my husband, and I know he would have done it for me.”

This article is reproduced with permission from STAT. It was first published on April 12, 2017. Find the original story here.


BY Grace Rubenstein, STAT

© 1996 – 2017 NewsHour Productions LLC. All Rights Reserved.


Two Existing Drugs Halt Neurodegeneration In Mice

( Researchers have made a major leap forward in the treatment of Alzheimer’s and Parkinson’s, after identifying two existing drugs that prevented brain cell death in mouse models of neurodegenerative disease.

In a new study, researchers from the Medical Research Council (MRC) in the United Kingdom reveal how a licensed antidepressant and a compound currently being trialled as a cancer drug blocked brain cell death, reduced brain shrinkage, and restored memory in mouse models of prion disease and frontotemporal dementia (FTD).

Study leader Prof. Giovanna Mallucci, of the MRC’s Toxicology Unit and the University of Cambridge in the U.K., and colleagues believe that their findings could lead to much-needed treatments for Alzheimer’s disease and other neurodegenerative diseases in as little as 2 to 3 years.

Clinical trials are needed to determine the safety and efficacy of the compounds for neurodegenerative disease in humans, but the fact that one of the compounds is already used for the treatment of depression could speed up the process.

Prof. Mallucci and her team recently reported their findings in the journal Brain.

Restoring Protein Production in Brain Cells

Neurodegenerative disease is an umbrella term for numerous conditions that involve the damage and loss of brain cells. Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis are all examples of neurodegenerative disease.

In a study published in 2013, Prof. Mallucci and her team uncovered a specific pathway that contributes to brain cell death.

The researchers found that misfolded proteins in the brain – which are abundant in the brains of patients with Alzheimer’s and other neurodegenerative disorders – over-activate an unfolded protein response, which hampers the production of new proteins in brain cells. This “starves” the brain cells and kills them.

In their 2013 study, the team used an experimental drug to reactivate protein production in brain cells. While it was successful in halting brain cell death, the compound was toxic to the pancreas and unsafe for human testing.

Now, the researchers have identified two new compounds that have not only proven effective for preventing brain cell death in mice, but they also had minimal side effects.

Neurodegeneration Prevented in Mice

For the new study, Prof. Mallucci and colleagues tested more than 1,000 compounds on roundworms, or Caenorhabditis elegans. The team notes that roundworms have a functioning nervous system and are commonly used to screen drugs that might be effective in mammals.

The researchers identified a number of compounds that showed promise for restoring protein production in the brain cells of neurodegenerative disease mouse models.

The team then tested these compounds on mouse models of prion disease – a group of neurodegenerative diseases caused by proteins called prions, which prompt the misfolding of healthy proteins – and a familial form of FTD.

FTD is a type of dementia caused by the loss of brain cells in the frontal lobes of the brain.

Two compounds were found to be effective: trazodone and dibenzoylmethane (DBM). Trazodone is a medication used for the treatment of depression, while DBM is a licorice-derived compound currently undergoing testing as an anti-cancer drug.

In most of the mouse models of prion disease, both drugs prevented signs of brain cell death by recovering protein production, and in FTD mouse models, the drugs restored memory.

Additionally, the researchers found that the drugs led to a decrease in brain shrinkage in both mouse models. Brain shrinkage is a hallmark of neurodegenerative disease.

The team notes that the side effects of both drugs were minimal.

An ‘Exciting First Step’ for the Treatment of Neurodegenerative Disease

The next step for the researchers is to conduct clinical trials to determine the safety and efficacy of trazodone and DBM for the treatment of neurodegenerative disease in humans.

Trazodone is the most promising candidate, since its safety has already been established in humans.

“We know that trazodone is safe to use in humans, so a clinical trial is now possible to test whether the protective effects of the drug we see on brain cells in mice with neurodegeneration also applies to people in the early stages of Alzheimer’s disease and other dementias.

We could know in 2 to 3 years whether this approach can slow down disease progression, which would be a very exciting first step in treating these disorders.” Prof. Giovanna Mallucci

Dr. Doug Brown, director of research and development at the Alzheimer’s Society in the U.K., says that he is “excited by the potential of these findings.”

“They show that a treatment approach originally discovered while researching prion disease might also work to prevent the death of brain cells in some forms of dementia,” he adds.

“This research is at a very early stage and has not yet been tested in people – but as one of the drugs is already available as a treatment for depression, the time taken to get from the lab to the pharmacy could be dramatically reduced.”


Written by Honor Whiteman

Healthline Media UK Ltd, Brighton, UK.

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