Dementia

Over the Counter Supplements to Improve Your Memory – Don’t Waste Your Money

Anyone who watches television these days is inundated by ads for supplements promising to improve your memory and your mental processing speed. In this post I will write about the evidence, or lack thereof that any of these supplements do what they promise.

Prevagen

The active ingredient in Prevagen is apoaequorin. It is a calcium binding protein found in luminescent jellyfish. When combined with calcium it causes bioluminescence (like a lighting bug). The manufacturer claims that taking Prevagen helps with brain health and improves aging related memory loss. The ads include testimonials from older people who say that Prevagen improved their memory.

There has been one clinical trial comparing apaequorin with placebo for improved verbal learning. It showed no benefit overall, but a subgroup analysis of people who had normal cognitive tests at baseline showed a slight improvement. Subgroup analyses in clinical trials are notoriously inaccurate. The FDA has not approved apaequorin for memory loss or for anything else.

In fact, apaequorin is a fairly large protein molecule, which means it is very unlikely to be absorbed into the blood stream at all. Proteins are broken down by acid in the stomach to their component amino acids and small peptides.

The bottom line is that Prevagen might combine with some calcium in your intestine and make the inside of your intestine glow in the dark, but it never leaves the intestine and so cannot possibly help your memory or your verbal learning. Any memory improvement that people report is almost certainly a placebo effect. The people giving testimonials on the Prevagen ads are actors reading from a script.

Balance of Nature

Balance of Nature sells fruit and vegetable supplements in capsules. The ads, like Prevagen, use actors reading a script. Like Prevagen, these fake testimonials report improvement in memory and learning. Here is the ingredients label for Balance of Nature fruit capsules:

Supplement Facts
Serving size: 3 capsules
Servings per container: 30
Amount per serving
Calories 10
Total Carbohydrate 2g
%DV*
<1%
Maintain Blend 731 mg
† Tomato (fruit), Papaya (fruit), Banana (fruit), Apple (fruit), Grape (fruit), Wild Blueberry
(fruit), Strawberry (fruit), Aloe Vera (leaf)
Protect Blend 719mg
† Orange (fruit), Tart Cherry (fruit), Cranberry
(fruit), Wild Blueberry (fruit), Grape (fruit),
Apple (fruit), Grapefruit (fruit), Aloe Vera (leaf)
Repair Blend 561mg Raspberry (fruit), Pineapple (fruit), Mango
(fruit), Sweet Cherry (fruit), Lemon (fruit),
Aloe Vera (leaf) * Percent Daily Values (DV are based
on a 2,000 calorie diet.
†Daily Value (DV) not established.
Other ingredients: Vegetable Capsules (cellulose).

Here is the ingredients label for the vegetable capsules:

Supplement Facts
Serving size: 3 capsules
Servings per container: 30
Amount per serving
Calories 5
Total Carbohydrate 1g
%DV*
<1%
Maintain Blend 720mg Broccoli (whole head), Spinach (leaf), Soybean (seed), Green Cabbage (head), Wheatgrass (leaves),
Kale (leaf), Cauliflower (whole head), Celery (stalk),
White Onion (bulb), Zucchini (fruit)
Protect Blend 713mg Garlic (clove), Red Cabbage (head), Red Onion (bulb), Soybean (seed), Carrot (root), Kale (leaf), Cayenne Pepper (fruit & seeds), Shiitake Mushroom
(whole), Wheatgrass (leaves), Sweet Potato (tuber)
Repair Blend 576mg Carrot (root), Kale (leaf), Green Onion (scape), Soybean (seed), Spinach (leaf), Cauliflower (whole
head), Celery (stalk), Zucchini (fruit) * Percent Daily Values (DV) are based
on a 2,000 calorie diet.
†Daily Value (DV) not established.
Other ingredients: Vegetable Capsules (cellulose). Contains: Soy.

There is no question that all of these fruits and vegetables are good for you, but only if you eat them! You could not possibly get enough fruits, vegetables and fiber to do you any good from capsules. There is absolutely no evidence that these supplement capsules have any effect on your memory or anything else except your pocketbook. A bottle of both kinds of supplements costs about $90.00. I would suggest you take that $90 and go to the grocery store and buy real fruits and vegetables!

Ginko Biloba

Ginko Biloba îs an extract from the leaves of the Ginko tree. It has been used in chinese herbal medicine for centuries. The extract contains numerous compounds and extracts sold over the counter are not standardized and may have different combinations of these various compounds. Claims for ginkgo biloba include improved blood circulation, effects on symptoms of old age, and improved memory.

Some older studies did show some effects, but newer well designed studies show that these effects are no greater than the people who take placebo. A meta analysis (a review of multiple studies) showed that ginkgo biloba extract had no effect in the prevention of dementia.

Does anything improve memory and/or prevent dementia?

The answer is yes, but it’s not a pill or a supplement. Here are some things that improve memory and decrease the risk of dementia (they are going to look familiar):

  • Staying mentally active (reading books, learning new skills, writing, etc)
  • Regular exercise (especially walking outside)
  • Eating unprocessed foods, especially fruits and vegetables
  • Maintaining an active social life (time spent with friends and family)
  • Getting 7-8 hours sleep per night

Bottom Line

Heavily advertised supplements work no better than placebo to improve brain health or memory in older adults or anyone else. Although ginkgo biloba has been used in chinese medicine for centuries, the evidence shows that it too works no better than placebo.

Lifestyle changes outlined above are the only things that have been shown to improve memory and decrease the risk of dementia.

Dementia: How to Reduce Your Risk

In my previous post, I described two population studies that showed that some people who had the structural brain changes of Alzheimer’s disease showed no evidence of dementia during their lives. How did their brains become so resilient? That is the subject of this post.

Sleep

There is a drainage system in the brain that removes beta amyloid proteins that can accumulate to cause Alzheimer’s disease. This drainage system only operates in stage 4 sleep. The problem is, of course, that elderly people who are at the highest risk of Alzheimer’s disease tend to have less deep stage 4 sleep. Nonetheless, getting adequate sleep significantly decreases the risk of Alzheimer’s disease. Sleep deprivation even in midlife is associated with an increased risk of developing Alzheimer’s disease later on in life. Adequate sleep for the vast majority of people means 7-9 hours of sleep a night. There are many other health benefits of adequate sleep (and conversely many health risks with chronic sleep deprivation). If you would like to learn more about sleep there is an excellent book by Matthew Walker called Why We Sleep. He also has a podcast if you prefer to listen rather than read. His podcast is called the Matt Walker Podcast.

Purpose in Life

A sense of purpose in your life substantially reduces your risk of developing Alzheimer’s disease. If your job gives you a sense of purpose, then continue to work as long as your health (or your employer) permits. If you are already retired, then find something to do that gives you a sense of purpose. It could be volunteer work or a part time job, or a hobby that you find meaningful. Anything you do that helps other people is more likely to give you a sense of purpose.

Good Nutrition

The subject of nutrition keeps coming up whenever we discuss any health topic. Eating a nutritious diet including high fiber, minimally processed foods decreases your risk of developing dementia. Here is a link to my previous post on good nutrition: Good Nutrition: A Review of the Evidence

Exercise

Regular exercise reduces the risk of developing Alzheimer’s disease. Although any regular exercise including walking reduces risk, the kind of exercise does matter somewhat. Walking out of doors especially on trails in parks stimulates your brain because you have to pay attention to where to put your feet. Even if you live in a city, you likely have access to parks with walking trails. Even walking several blocks in the city outside stimulates your brain more than walking on a treadmill at home or in a gym.

Drink less alcohol

Heavy alcohol use substantially increases the risk of developing dementia, but light to moderate alcohol use may actually be protective. 14 or less units of alcohol per week does not increase your risk of dementia and may somewhat reduce your risk. A unit of alcohol is 10 ml (about 1/3 of an oz) of pure alcohol. Here is a link to a calculator that calculates how many units are in multiple kinds of alcoholic beverages: Alcohol Change Unit Calculator.

Don’t Smoke

Smoking increases your risk of developing Alzheimer’s disease by 60%. If you do smoke, quit. If you don’t smoke, don’t start.

Learn New Skills

When you learn new things, your brain forms new connections and the more new connections are formed, the more resilient is your brain. This resilience helps protect your brain function and substantially decreases your risk of developing dementia. It is important to do a variety of things that stimulate your brain. Just doing crossword puzzles or other games that purport to stimulate your brain have not been shown to decrease the risk of dementia. Start keeping a journal, write a blog, learn a new skill that requires eye-hand coordination. Take art lessons, or woodworking lessons, or lessons in any other new skill that strikes your fancy. Engaging in creative activities helps form a variety of new brain connections, and those are what protect you from dementia.

Social Contacts

Frequent face to face contact with friends and family substantially reduces your risk of developing dementia. We are social animals and our brains were designed to interact with others. Loneliness may increase the risk of developing dementia by as much as 40%. Conversely, a good social support system can reduce the risk of developing dementia by as much as 60%. Contact with others mainly through electronic social media may reduce the risk of dementia somewhat, but interactive face to face contact with others seems to be necessary for reducing dementia risk substantially.

Bottom Line

There is nothing you can do that reduces your risk of developing dementia to zero. You can, however reduce your risk quite a bit. Get 7-9 hours of sleep a night. Avoid highly processed foods. Exercise regularly, especially outside if possible. Drink 14 units or less of alcohol per week. Don’t smoke. Maintain a sense of purpose in your life. Continually learn new skills. Maintain an active social network.

If you do all of these things, you stand a good chance of remaining alert and having a productive life well into your eighties and nineties.

Dementia: The Scourge of Old Age

This is the fourth in a series of posts about chronic disease.

Age is the biggest risk factor for dementia. You can’t keep from getting older, but there are things that decrease the risk of dementia at any age. In this post I will discuss the types of dementia, the symptoms associated with each and what is known about the epidemiology of each type. In the next post I will talk about ways to reduce your risk of dementia.

Statistics

In the US, 5% of 70-79 year olds have dementia. For 80-89 year olds, 17% have dementia and for people 90 or over, 31% have dementia. The prevalence of dementia is not distributed evenly across the population. The lower the educational level, the higher the risk of dementia over age 70. The prevalence is also increased for African Americans and for hispanics. Death rates for dementia have marked regional differences. Southern states have the highest death rates. Tennessee has the highest death rate at 90.1 per 100,000 and New York has the lowest at 43 per 100,000. Women are slightly more at risk than men and people who are married are at lower risk than people who are unmarried.

Normal brain aging

As people get older it is normal for brain function to slow down some. Here are some signs of normal brain aging that are not dementia, early or otherwise: forgetting names and then remembering them later; going into a room and forgetting what you came for; forgetting where you put your keys; slower recall of dates and events.

What is dementia?

Dementia is not just slowing down or forgetting. Dementia is a loss of brain function that significantly interferes with daily life. It can range from mild cognitive impairment to complete inability to care for oneself. People with dementia don’t just forget recent events, they forget how to do things they have always done, like cooking from a recipe or balancing a checkbook. They can wander and get lost in a familiar neighborhood. Recent memory is so impaired that they will often ask the same question over and over again. They may have trouble expressing themselves verbally and/or in writing. Certain types of dementia have some distinct symptoms, which I will talk about later in this post. Here is a link to a CDC web page that describes 10 warning signs of early dementia: 10 Warning Signs of Alzheimers. People tend to equate dementia with Alzheimer’s disease, and that is certainly the most common type (about 75%) but there are other causes for dementia as well.

Alzheimer’s Disease

In 1906 Alois Alzheimer, a psychiatrist and neuroanatomist, described a severe disease of the cerebral cortex in a 50 year old woman at a psychiatry meeting in Germany. She had severe memory loss, speech disturbance, sleep disturbance, paranoia and confusion. He followed her in the hospital until she died 5 years later. An autopsy was done and the microscopic slides of the brain showed distinctive plaques and neurofibrillary tangles. He presented the clinical history and autopsy report at the meeting.

This pattern of progressive dementia associated with the brain findings of plaques and neurofibrillary tangles became known as Alzheimer’s disease. It was initially also known as pre-senile dementia, because the first patients described were relatively young. It was only later that it was discovered that the dementia commonly associated with old age had the same microscopic brain findings of plaques and neurofibrillary tangles, so the Alzheimer’s disease label came to describe dementia at any age associated with the characteristic microscopic brain abnormalities. Research has subsequently shown that the plaques are made up of a protein called beta amyloid and the tangles are made up of another protein called tau.

There is no lab test or brain scan that will confirm a diagnosis of Alzheimer’s disease. A firm diagnosis can only be made by examining the brain after the patient dies. A diagnosis of probable Alzheimer’s disease can be made with about 90% certainty based on slow onset and gradual progression of dementia.

Alzheimer’s disease is not curable. There are some medicines that have been approved for Alzheimer’s, but they don’t work very well. Most studies of these medicines show cognitive improvement of about two points on a one hundred point measurement scale. Although statistically significant, clinical significance is doubtful.

Lewy Body Dementia

Lewy body dementia is the second most common cause of dementia after Alzheimer’s disease. It affects about 1.4 million Americans. Brain autopsies show clumps of protein called Lewy bodies. They are made of a normal brain protein called alpha-synuclein. A mutation of the protein causes it to be misfolded and accumulate in nerve cells in the brain. People with Lewy body dementia have very vivid hallucinations and movement disorders similar to Parkinson’s disease. They also have fluctuating levels of consciousness, sometimes being very confused and sometimes having moments of clarity. There is no cure and it leads to death in 4-6 years. This is the type of dementia that the actor Robin Williams had.

Vascular Dementia

Vascular dementia is caused by blockage of small arteries in the brain. The same risk factors for heart disease and stroke are also risk factors for vascular dementia. It is thought that vascular dementia occurs because of a series of tiny strokes in the brain. Sometimes vascular dementia proceeds in a stepwise fashion, but it can also progress gradually, just like Alzheimer’s disease. In that case it is clinically indistinguishable from Alzheimer’s disease and it is also not uncommon for people with vascular dementia to have Alzheimer’s disease as well. About 5-10% of people with dementia have vascular dementia alone. Just as with Alzheimer’s disease, there is no specific lab test or brain scan that reliably makes a diagnosis of vascular dementia. Once again, a firm diagnosis can only be made at autopsy. There is no treatment other than prevention.

Pick Disease

Pick disease is also called frontotemporal dementia or frontotemporal degeneration. It is less common than Alzheimer’s disease, Lewy body dementia and vascular dementia, but it tends to occur at much younger ages, often in the 40’s or 50’s. It is sufficiently rare that the epidemiology is not well understood. The brain cells of people with Pick disease have round bodies called pick bodies. They are made of tau fibrils, the same protein that is in the neurofibrillary tangles in the brains of people with Alzheimer’s disease. The symptoms of Pick disease are primarily loss of control of behavior as well as language difficulties. It is often initially misdiagnosed as a psychiatric disorder. There are three variants. One involves mostly behavioral abnormalities like mood changes, personality changes, inappropriate behavior, social withdrawal, and repetitive behaviors. The second variant is called primary progressive aphasia. People with this variant have progressive loss of the ability to speak, write and understand language. The third variant involves difficulty with movement and balance. The cause is unknown and there is no treatment. People with Pick disease eventually die from it, but can survive as long as ten years. This is a terrible disease. It is fortunate that it is relatively rare.

Treatable Causes of Dementia

Although the vast majority of people with dementia have one of the four diseases described above that are progressive and incurable, there are a few causes of dementia that are reversible. That is why we do blood tests, CT scans and MRI’s on people newly diagnosed with dementia, because every now and then we find one of the treatable causes. Treatable causes of dementia are: hypothyroidism (low thyroid hormone); vitamin B12 or folate deficiency; infections of the brain (syphilis, Lyme disease and others); brain tumors; subdural hematomas (blood clots under the membrane that covers the brain); normal pressure hydrocephalus (blockage of the flow of spinal fluid out of the brain). Depression in older people can look like dementia and should always be ruled out.

I will give you an idea about how uncommon treatable dementia is in clinical practice. In forty years of primary care practice, despite dutifully doing the recommended evaluation on every patient with a new diagnosis of dementia I found normal pressure hydrocephalus once and none of the others. That is not to say that I did not see and treat those other conditions, but none of them ever presented as undiagnosed dementia.

Brain changes of Alzheimer’s Disease Without Dementia

There have been two population studies that started with older people who had no evidence of dementia and followed them for years with followup tests for dementia. In both of them a small percentage of people who had plaques and neurofibrillary tangles typical of Alzheimer’s disease had no evidence of dementia on the tests during life.

The Nun Study

The participants in this study were Catholic sisters, who were members of the School Sisters of Notre Dame congregation living in the United States. All sisters born before 1917 were asked to participate in the study. There were 678 sisters who agreed to participate and they were all enrolled in the study between 1991 and 1993. Permission to do autopsies after their deaths was obtained from 95% of the sisters. A small group had typical plaques and neurofibrillary tangles in their brains at autopsy, but had no evidence for dementia while they were alive. Here is a link to one of the papers from that study: The Nun Study.

Adult Changes in Thought Study

This study recruited 4690 subjects from the Seattle area. Again, participants had no evidence of dementia at the beginning of the study. Tests for dementia were done periodically for all the living participants. Permission to do autopsies after their deaths was obtained from 25% of this group. Like the Nun Study, a small group of these people had typical Alzheimer’s disease changes in their brains, but no evidence of dementia while they were alive. Here is a link to the description of that study: Adult Changes in Thought Study.

Cognitive Reserve

Both of the studies described above suggest that some people have or can develop some sort of cognitive reserve that preserves brain function even in the presence of structural changes in the brain. I will talk about evidence for how that may happen in the next post.