Sunday, May 6, 2012

Some New Observational Studies and Alzheimer's Dementia

I'm gearing up for a talk later this month for the Massachusetts Psychiatric Society Geriatric Interest Group, which means I'm trying to keep abreast of all the latest diet and dementia studies.  A couple new big ones came out, both from groups with which we are familiar.  The first is from the Nurse's Health Study which purports that eating berries can protect us from cognitive decline via the magical power of flavinoids.  The second paper is from the same group who linked consumption of organ meats with dementia in northern Manhattan in one of those dreaded dietary pattern studies.

They have similar designs.  Follow a large group of people without dementia at baseline for a number of years, tracking demographic and dietary information along the way. Track new diagnoses of dementia or test people with basic cognitive screens on a regular basis.  In addition, the members of the Washington Heights/Hamilton Heights Columbia Aging Project (WHICAP) had plasma beta amyloid peptide measured.  It is thought that blood levels of beta amyloid correlate with brain levels, and other studies have shown that higher beta amyloid in the plasma correlates with the onset of dementia.

In the WHICAP crew, those who had higher intake of omega 3 fatty acids had lower levels of plasma beta amyloid, even after adjusting for confounders.  This finding would make biologic sense, as omega 3 fatty acids in lipid rafts help cleave amyloid precursor protein (APP) into harmless bits, whereas arachidonic acid in the same place allows for APP to be made into beta amyloid, the component of those plaques that build up in the brain.  However, the dietary sources of omega 3 PUFAs are listed as "salad dressing, fish, poultry, margarine, and nuts," which, excepting the fish, are generally terrific dietary sources of omega 6 PUFA, not omega 3.  To get an idea of the confounders, "Participants with higher plasma levels of [beta amyloid] peptide were older and less educated and had lower intakes of omega 3 PUFA, omega 6 PUFA, and MUFA…" and "Participants with higher omega 3 PUFA, higher omega 6 PUFA, or higher MUFA intakes had a higher education, were more likely to be white or black and less likely to be Hispanic."

The researchers tried to adjust for subtype of omega 3 PUFA (bless their hearts, considering they were working from food frequency questionnaires) and "none of the subtypes of omega 3 PUFA was significantly associated with the level of beta amyloid, suggesting that overall intake of omega 3 PUFAs might play a more important role."  (Or maybe it all just suggests that people who eat "healthy" in general eat fairly healthy who are also better educated and wealthier have a lower risk of dementia and less inflammation on board, as plasma beta amyloid is linked with inflammation and oxidative stress.)

In rodents models, a bit of omega 3 in the chow can reduce plasma beta amyloid by a whopping 70% in a matter of weeks compared to "low DHA control chow" and plaque burden in the brain is "reduced by 40.3%."  In human experiments (only one of which measured plasma beta amyloid and have been small), there hasn't been much benefit to adding omega 3s in folks with dementia, though those with mild cognitve impairment might be helped.  I'm guessing that it is difficult for a human to be quite as depleted of omega 3 and topped off with omega 6 as much as those lab rats with their shudder-worthy processed rat chow.

In the Nurses Health Study, blueberries and strawberries take center stage.  Nurses who admit to eating buckets of them (chock full of the antioxidant anthocyanidin) had better cognitive scores as the study went forward over the decades.  And while according to Walter Willett the confounders are easily accounted for, you may not be surprised to know that the berry eating nurses were wealthier, more likely to exercise, more likely to eat fish, and more likely to eat more calories period.

But, in the interest of some discussion, yes, bioflavinoids are very sexy.  In the Nurses Health Study, the riches sources were strawberries and blueberries, but tea, oranges, and apples are also common sources.  The anthocyanidins in the berries, in particular, are known to be able to cross the blood brain barrier and work in the hippocampus, a central brain area of learning and memory.  Not only are they antioxidants, but might also directly deactivate cellular inflammatory mechanisms.

In short, I concur that fish and berries are good for you.  However, these studies were not designed to prove that by any means, but rather to point out some interesting population trends as related to dementia and cognitive decline.  Consider them pointed out.

I'm a bit sick of these sorts of studies, to be honest.


  1. You and me both. I am especially sick of studies purporting to show that fibre or folate is beneficial, based on consumption of leafy greens or fruit.
    What about electrolytes? Ascorbate? Carotenoids? Polyphhenols? Micronutrients?

    The apparent fact that eating most veges kills almost as many people as eating least veges is never satisfactorily explained.
    Perhaps the fibre, or the folate, is killing these unfortunates....

  2. The basic problem is it is a lot of information to analyze. There are thousands of nutritional variables to analyze and a lot of these studies involve either supraphysiological doses or gross estimates of the variable(s) in question. In real life,we can't seem to determine something as basic as the daily requirement of Vitamin D.

    There is probably more variability on the diagnostic side. There is little doubt that much of what passes for Alzheimer's disease is really vascular dementia. In correctly including anywhere from 10-30% or patients with a vascular etiology will make it seem like nutritional factors that address vascular dementia improves Alzheimers.

    More science would help. As a chemist before I became a psychiatrist, I would like to seem some redox potentials and physical chemistry of the antioxidants done. That could also lead to insights into disease mechanisms. An inexpensive marker for true AD or at least the heterogeneous diseases we are calling AD would also be clarifying.

  3. These studies often confuse cognitive decline with AD.
    I read somewhere recently that 20% of those diagnosed with Parkinson's have no sign of the brain disease at autopsy.

    Perhaps some of these annoying studies are actually publicity exercises to get around the even more annoying FDA restrictions on health claims; a silly health claim in the media is safer than a science-based claim on the packaging.

    for example:

    " In the case of Fleminger, Inc., which sells green tea and filed a health claim petition in 2004 to highlight green tea's anti-cancer properties, the FDA suggested that this disclaimer be added to the health claim:

    "FDA concludes that it is highly unlikely that green tea reduces the risk" of breast cancer or prostate cancer.

    Obviously, this essentially contradicts the health claim.

    So, in 2010 (after a petition to review the FDA's disclaimer was denied), the FDA threatened to seize Fleminger's products if they did not use the exact disclaimer above.

    Eventually the FDA sent a revised claim, which still negated the point of the health claim:

    "Green tea may reduce the risk of breast or prostate cancer. FDA does not agree that green tea may reduce the risk because there is very little scientific evidence for the claim."

    Fleminger took the case to court, where Judge Bryant ruled:

    "The FDA's language "effectively negates the substance–disease relationship claim altogether….There are less burdensome ways in which the FDA could indicate in a short, succinct and accurate disclaimer that it has not approved the claim without nullifying the claim altogether."

    quoted in

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  5. If I was worried about AD I would strap a pair of cellphones to my head:

    "In the experiment, scientists examined the effects of cell phone radiation on 96 mice that were genetically engineered to develop beta amyloid plaques and thus Alzheimer's-like symptoms. The mice normally developed the first signs of the disease around 6 months. By 8 months they were already experiencing cognitive declines.

    Both the Alzheimer's-prone mice and normal mice were then exposed to cell phone-level microwave radiation for two one-hour periods daily for seven to nine months.

    The study found that if cell phone exposure began before the genetically engineered mice started showing signs of Alzheimer's, they were less likely to develop symptoms later on in life.

    Furthermore, the genetically engineered mice that were were exposed to the cell phone radiation after they had already begun to show cognitive deficits generally saw their memory impairment disappear after several months of the radiation exposure."

    Cellphones beat Alzheimers?
    Now that's what I call evolution!

  6. The answer to Alzheimer's is staring everyone in the face. It's all about iron accumulation. We now know that the function of the Amyloid Precursor Protein is to enable iron export from neurons.

    It's a copper protein like ceruloplasmin which enables iron export from astrocytes. Copper supplementation has been tried and didn't work. The patients were almost certainly just as deficient for manganese as for copper. Iron isn't really toxic if there's enough copper and manganese.

  7. Just imagine a society where our toys and gadgets double as longevity enhancers, once consumer pressure deselects for harmful influences and advanced technology allows us to choose...
    Maybe the treckies have been right all along.

    @Jane, iron is mainly toxic in the context of inflammation and elevated insulin. The mechanism exists to regulate iron tightly, but is vulnerable to disease. Ergo, iron toxicity is a symptom of many diseases which magnifies the damage done.


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