{"id":223,"date":"2014-03-12T13:36:08","date_gmt":"2014-03-12T13:36:08","guid":{"rendered":"http:\/\/joshmitteldorf.peachpuff-wolverine-566518.hostingersite.com\/?p=223"},"modified":"2014-03-12T13:36:08","modified_gmt":"2014-03-12T13:36:08","slug":"mitigating-risk-of-alzheimers-disease-more-important-than-we-thought","status":"publish","type":"post","link":"https:\/\/scienceblog.com\/joshmitteldorf\/2014\/03\/12\/mitigating-risk-of-alzheimers-disease-more-important-than-we-thought\/","title":{"rendered":"Mitigating risk of Alzheimer’s Disease: More important than we thought"},"content":{"rendered":"

Recent re-analysis suggests that Alzheimer’s Disease ought to be ranked with cancer and heart disease as one of the most important mortality risks for older Americans. \u00a0Some of this risk is under our control.<\/em><\/p>\n

In a study published last week<\/a>, Bryan James and colleagues at Rush Univ. Medical Center in Chicago tell us that Alzheimer\u2019s Disease has been greatly under-reported as a cause of death. \u00a0According to current statistics, cancer and heart disease are tied for the top spot, each contributing almost \u00bc of all deaths in the US. \u00a0The new study says that AD should be right up there with heart disease and cancer, accounting for about \u2155 of US deaths. \u00a0If they are right, then these Big 3 diseases of old age together account for 70% of all deaths – not just deaths among the elderly.<\/p>\n

Previously, AD had been listed as number 6 by the US Center for Disease Control<\/a>, and the new study would move AD up to the #3 spot, which had previously been claimed by emphysema. \u00a0Emphysema is way behind cancer and heart disease, and predominantly affects smokers. \u00a0It\u2019s almost certainly true that AD has been under-reported, and it wouldn\u2019t take very much to move it up to #3; but whether AD really accounts for a 20% risk factor overall is less clear. \u00a0Let\u2019s take a look at their methodology. \u00a0(or if you like you can skip ahead: What can you do about your AD risk?<\/a>)<\/p>\n

What\u2019s wrong with this study?<\/strong><\/p>\n

The methodology of the study was straightforward. \u00a0For eight years, they tracked a group of about 2500 seniors, average age 78. \u00a0They learned if each person was diagnosed with AD, and if he died. \u00a0People diagnosed with AD had on average less than 4 years to live. \u00a0The mortality rate for people diagnosed with AD under age 85 was 4.3 times higher than otherwise (and 2.8 times higher if over 85). \u00a0These numbers (4.3 or 2.8) are called \u201chazzard ratios\u201d, and as it turns out, they are an easy statistic to work with, and translate straightforwardly into inferences about the mortality risk of a diagnosis of AD.<\/p>\n

The authors make the leap that this many deaths were attributable to AD, whether AD was listed as the cause of death or not. \u00a0Is this justified? \u00a0Think about it. \u00a0They are assuming that AD is the underlying cause and (for example) heart disease might be listed as the cause of death, but the heart disease was caused by an earlier diagnosis of AD. \u00a0But isn\u2019t it just as likely to be the other way around? \u00a0People in danger of a heart attack may undergo bypass surgery, as a result of which the brain is deprived of oxygen during surgery and cognitive impairment results<\/a>.<\/p>\n

Or maybe there are underlying conditions (e.g., high inflammation, metabolic syndrome) that put the patient at higher risk for both AD and cancer, and then the patient dies of cancer. \u00a0It\u2019s not right to assume that AD caused the cancer, or that this patient really died of AD.<\/p>\n

So the authors\u2019 conclusion that AD causes half a million deaths in the US every year is certainly overstated. \u00a0Nevertheless, they\u2019ve got a point, and AD almost certainly should be moved up to the #3 slot, especially for non-smokers. \u00a0I believe there\u2019s a lot of truth in the idea that mortality from AD is under-reported because the proximate cause of death is frequently something else. \u00a0If nothing else, depression and institutionalization frequently follow from dementia, and both are major mortality risk factors, under many guises. \u00a0Also, I believe in an \u201caging clock\u201d: regulation of the rate of aging that derives from hormones secreted in the brain. \u00a0It is not hard for me to believe that deterioration of the brain has a direct effect on aging, and through aging on other aspects of health.<\/p>\n

 <\/p>\n

Blood test predicts AD<\/strong><\/p>\n

Also reported this week was a blood test<\/a> that can predict (10 false positives out of 100) who will develop AD in the ensuing three years. \u00a0The work was reported in Nature Medicine<\/a> by Howard Federoff of Georgetown University. \u00a0Does the test offer a clue about the etiology of AD? \u00a0Not at all. \u00a0The test was developed using formal statistical methods. \u00a0They made lipid blood profiles for several hundred people over the age of 70, testing the specific types of fats present in the blood plasma. \u00a0Then they waited three years to see which of the people might be diagnosed with AD. \u00a0Then, after the fact, they went back and used a blind, brute-force computer search to test millions of combinations of different features in the lipid profiles to look for ways in which the people who developed AD might be consistently different from the people who didn\u2019t. \u00a0They then tested the test, applying it to a completely different group of people to see if the same test would work to predict AD for them. \u00a0It did.<\/p>\n

There is no biology in this approach; only mathematics, and authors of the paper do not try to parse the significance of their results.<\/p>\n

 <\/p>\n

What causes AD?<\/strong><\/p>\n

Medical science is not in agreement about the cause of AD, and it may be that the symptoms of cognitive impairment come from several causes, separately and together. \u00a0Up until a few years ago, there was a theory about amyloid plaques<\/a> in the brain, tiny accumulations of misfolded proteins that the body has failed to recycle. \u00a0But that theory has faded in popularity with evidence that the plaques may be an effect rather than cause of AD.<\/p>\n

 <\/p>\n

Apoptosis of otherwise healthy neurons?<\/strong> \u00a0or \u00a0is it
\nAmyloid plaques triggering an inflammatory attack on the brain?<\/strong><\/p>\n

Everyone agrees that the proximate cause of dementia symptoms is the loss of nerve cells in the brain. \u00a0Curiously, it seems that healthy neurons may be \u201ccommitting suicide\u201d, eliminating themselves via apoptosis [ Ref1<\/a> , Ref2<\/a> , Ref3<\/a> ]. \u00a0For people of my school, this is yet one more instance of the body\u2019s suicide program, the finite life span that has been programmed into our genes by natural selection for the purpose of leveling the death rate and stabilizing ecosystems. \u00a0People who believe that aging is not programmed tell the story in terms of the amyloid plaques triggering an immune response, and it is the inflammation that leads to apoptosis. \u00a0In any case, we all agree that inflammation is a risk factor for AD, and that anti-inflammatory supplements and drugs can lower the risk of AD. \u00a0(Anti-inflammatories also offer protection against cancer and heart disease.)<\/p>\n

<\/a><\/p>\n

 <\/p>\n

What can you do control your risk of AD?<\/strong><\/p>\n

The usual stuff<\/a>. \u00a0Weight control, exercise, and most everything else you do to extend life expectancy lowers risk of AD along the way. \u00a0Remaining mentally active, learning new skills, putting yourself in new situations and taking on new challenges – these are ways to keep ourselves alive and aware, and they also reduce risk of AD<\/p>\n

Anti-inflammatories are especially helpful. \u00a0Curcumin<\/a> (turmeric) is an herbal anti-inflammatory that deserves special mention because of the many studies<\/a> finding a protective effect in test tubes, mice, and humans. \u00a0In India, dementia is only \u00bc as common<\/a> as in Europe and America, possibly because of turmeric in the diet. \u00a0There is evidence to recommend fish oil<\/a>, and also studies in which fish oil does not work<\/a>. \u00a0Daily, low-dose ibuprofen lowers the risk of AD, and there are mixed reports of whether aspirin does as well<\/a>.<\/p>\n

A great number of traditional herbs have been shown to be neuroprotective. \u00a0This review of neuroprotective herbs<\/a> mentions Ashwaghanda<\/a>, Bacopa<\/a>, Carnitine<\/a>, Melatonin<\/a>, CoQ10, Garlic, Vitamin D, Ginseng, and Ginkgo biloba. Here is another review<\/a> of herbs that might be useful for AD. \u00a0None of these is a cure for AD, but there is some clinical evidence for benefit from each. \u00a0Readers familiar with my AgingAdvice<\/a> page know that I like melatonin and vitamin D for other reasons as well.<\/p>\n

Blueberries<\/a> and perhaps other berries<\/a> are protective. \u00a0A substance called fisetin<\/a> (chemical cousin of quercetin) found in fruits and berries may be partly responsible. \u00a0Soy products contain phytoestrogens – chemicals which resemble female hormones. \u00a0Twenty years back, it was noticed that east Asians who moved to America and adopted an American diet had lower risk of AD, and it was hypothesized that phytoestrogens from soy might increase risk of AD<\/a>. \u00a0But more recently several studies seem to point in the opposite direction, that soy might protect against AD [ Ref1<\/a> , Ref2<\/a> , Ref3<\/a> ].<\/p>\n

I\u2019ve reported (here<\/a> and here<\/a>) that since November I\u2019ve been taking deprenyl (~1mg daily) and I find that it\u2019s making me happy and increasing my energy, much to my consternation since I\u2019m constitutionally anti-anti-depressant. \u00a0Deprenyl (sold as Selegiline or Emsam) is neuroprotective and it\u2019s on the short list of drugs that consistently augment the life span of rodents in the lab.<\/p>\n

 <\/p>\n

And what is the payoff for avoiding AD?<\/strong><\/p>\n

According to the new hypothesis of James, 20% of mortality risk at all ages comes directly or indirectly from dementia. \u00a0Based on a 20% reduction in mortality, I calculate (using CDC life tables for 2010) that if we can greatly reduce risk of AD with all the above measures, starting (for example) at age 50, we might add 2\u00bd years to life expectancy.\"\"<\/p>\n

 <\/p>\n

A horrible way to die, for some<\/strong><\/p>\n

The stereotypical AD patient is depressed and isolated by failure of his memory and inability to communicate. \u00a0And sadly, this is the norm as patients become disoriented and frustrated with inability to function. \u00a0But some AD patients become happy<\/a> and grateful, detached from the worries that tied them down, occasionally euphoric.<\/p>\n

 <\/p>\n

Who will I be after I die? \u00a0Who was I before I was born?<\/strong><\/p>\n

We think of life and death like 1 and 0, like on and off, without a gray zone. \u00a0But it took time for our physical selves to develop, and our brains to connect up in ways that support the conception of a separate self. \u00a0In AD, the self takes about the same amount of time to disintegrate as it took to form.<\/p>\n

Most of us have no memories before we were three. \u00a0Perhaps it takes three years for the brain to organize itself around time and events, inner self and outer world. \u00a0All that individuation that happened during the \u201cterrible twos\u201d is no longer part of our remembered life. \u00a0All that bewilderment, the wonder and constant questioning, a state of deep becoming.<\/p>\n

I think of AD as the mirror image of the child\u2019s individuation, the gradual dissolution of self. \u00a0For many of us, that prospect is terrifying, but remember that the infant also found it terrifying to become a separate self. \u00a0If there\u2019s any benefit we can hope to derive from a lifetime of accumulated wisdom, let it be the ability to know fear for what it is: merely a genetic program, evolved to protect the individual genome and improve our chances of passing<\/p>\n","protected":false},"excerpt":{"rendered":"

Recent re-analysis suggests that Alzheimer’s Disease ought to be ranked with cancer and heart disease as one of the most important mortality risks for older Americans. \u00a0Some of this risk is under our control. In a study published last week, Bryan James and colleagues at Rush Univ. Medical Center in Chicago tell us that Alzheimer\u2019s … Read more<\/a><\/p>\n","protected":false},"author":65,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"jetpack_post_was_ever_published":false,"_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":false,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_memberships_contains_paid_content":false,"footnotes":""},"categories":[1],"tags":[],"class_list":["post-223","post","type-post","status-publish","format-standard","hentry","category-uncategorized"],"yoast_head":"\nMitigating risk of Alzheimer's Disease: More important than we thought - Josh Mitteldorf<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/scienceblog.com\/joshmitteldorf\/2014\/03\/12\/mitigating-risk-of-alzheimers-disease-more-important-than-we-thought\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Mitigating risk of Alzheimer's Disease: More important than we thought\" \/>\n<meta property=\"og:description\" content=\"Recent re-analysis suggests that Alzheimer’s Disease ought to be ranked with cancer and heart disease as one of the most important mortality risks for older Americans. \u00a0Some of this risk is under our control. 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The surprising fact that our bodies are genetically programmed to age and to die offers an enormous opportunity for medical intervention. It may be that therapies to slow the progress of aging need not repair or regenerate anything, but only need to interfere with an existing program of self-destruction. Mitteldorf has taught a weekly yoga class for thirty years. He is an advocate for vigorous self care, including exercise, meditation and caloric restriction. After earning a PhD in astrophysicist, Mitteldorf moved to evolutionary biology as a primary field in 1996. He has taught at Harvard, Berkeley, Bryn Mawr, LaSalle and Temple University. He is presently affiliated with MIT as a visiting scholar. In private life, Mitteldorf is an advocate for election integrity as well as public health. He is an avid amateur musician, playing piano in chamber groups, French horn in community orchestras. His two daughters are among the first children adopted from China in the mid-1980s. Much to the surprise of evolutionary biologists, genetic experiments indicate that aging has been selected as an adaptation for its own sake. This poses a conundrum: the impact of aging on individual fitness is wholly negative, so aging must be regarded as a kind of evolutionary altruism. Unlike other forms of evolutionary altruism, aging offers benefits to the community that are weak, and not well focussed on near kin of the altruist. This makes the mechanism challenging to understand and to model. more at http:\\\/\\\/mathforum.org\\\/~josh\",\"sameAs\":[\"http:\\\/\\\/AgingAdvice.org\"],\"url\":\"https:\\\/\\\/scienceblog.com\\\/joshmitteldorf\\\/author\\\/joshmitteldorf\\\/\"}]}<\/script>\n<!-- \/ Yoast SEO Premium plugin. -->","yoast_head_json":{"title":"Mitigating risk of Alzheimer's Disease: More important than we thought - Josh Mitteldorf","robots":{"index":"index","follow":"follow","max-snippet":"max-snippet:-1","max-image-preview":"max-image-preview:large","max-video-preview":"max-video-preview:-1"},"canonical":"https:\/\/scienceblog.com\/joshmitteldorf\/2014\/03\/12\/mitigating-risk-of-alzheimers-disease-more-important-than-we-thought\/","og_locale":"en_US","og_type":"article","og_title":"Mitigating risk of Alzheimer's Disease: More important than we thought","og_description":"Recent re-analysis suggests that Alzheimer’s Disease ought to be ranked with cancer and heart disease as one of the most important mortality risks for older Americans. \u00a0Some of this risk is under our control. 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The surprising fact that our bodies are genetically programmed to age and to die offers an enormous opportunity for medical intervention. It may be that therapies to slow the progress of aging need not repair or regenerate anything, but only need to interfere with an existing program of self-destruction. Mitteldorf has taught a weekly yoga class for thirty years. He is an advocate for vigorous self care, including exercise, meditation and caloric restriction. After earning a PhD in astrophysicist, Mitteldorf moved to evolutionary biology as a primary field in 1996. He has taught at Harvard, Berkeley, Bryn Mawr, LaSalle and Temple University. He is presently affiliated with MIT as a visiting scholar. In private life, Mitteldorf is an advocate for election integrity as well as public health. He is an avid amateur musician, playing piano in chamber groups, French horn in community orchestras. His two daughters are among the first children adopted from China in the mid-1980s. Much to the surprise of evolutionary biologists, genetic experiments indicate that aging has been selected as an adaptation for its own sake. This poses a conundrum: the impact of aging on individual fitness is wholly negative, so aging must be regarded as a kind of evolutionary altruism. Unlike other forms of evolutionary altruism, aging offers benefits to the community that are weak, and not well focussed on near kin of the altruist. 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