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Low body weight associated with dementia risk?


Guest David

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Guest David

I was just reading about this surprising study, in which it was found that obese individuals were less likely to suffer from dementia than their normal weight peers -- and underweight individuals were found to be by far the most likely to develop dementia.  This epidemiological study is not the type that can prove cause and effect, but the results are noteworthy.

 

http://www.philly.com/philly/health/topics/HealthDay698288_20150410_Could_Obesity_Help_Protect_Against_Dementia_.html

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Guest Scott McClatchey

My take on it is this: there are numerous epidemiological studies that on the surface seem to indicate that being overweight is protective vs. death or (in this case) dementia. The problem with these is, as I see it, controlling for smoking and for chronic disease. Both smoking and for chronic disease (e.g., Crohn disease, kidney disease, etc.) make people thin, but predispose to death, dementia, etc. Researchers try to "control" for smoking (but not chronic disease) with statistical methods (e.g., multiple linear regression), but I think that this fails. When more careful epidemiological research is done that *excludes* smoking and chronic disease, the apparent protective effect of overweight or obesity disappears or is reversed. For example, In a huge, laborious and carefully done meta-analysis, the apparent J-curve of death rate vs. BMI has a rise at lower BMIs that appears to be related to smoking. “Collaborative analyses were undertaken of baseline BMI versus mortality in 57 prospective studies with 894 576 participants…[above a BMI of 25] each 5 kg/m2 higher BMI was on average associated with about 30% higher overall mortality… The definite excess mortality below 22•5 kg/m2 is due mainly to smoking-related diseases” www.thelancet.com/journals/lancet/article/PIIS0140-6736%2809%2960318-4/fulltext?version=printerFriendly (free full text); www.crsociety.org/topic/11129-relationship-between-bmi-and-disease-and-longevity/ To avoid dementia in old age, don’t be overweight or obese when you are young. Yet another study shows this: www.neurology.org/content/76/18/1568.abstract. This one is particularly powerful because it studied a large number of twins, and found that in cases where one twin was normal weight and one overweight or obese, the overweight or obese twin had a much higher rate of dementia.

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First, please do me and you and everyone on the Forum a favor: register on the Forums and log in each time before you post! Scott, you've registered and apparently just forgot to log in; "Guest_David", It's fine if you want to use a pseudonym, but registering and logging in will ensure that you can't be impersonated and will make it easier to keep track of your questions (you can set up your preferences to send you an email when someone responds to one of your posts or a thread in which you're interested), input, and progress.

 

In general, I agree with Scott's points. Many of the problems with using BMI/leanness/obesity studies human Calorie restriction prospects on  total mortality also apply to Alzheimer's (not sure about other forms of dementia), because AD itself causes weight loss that begins at least 5 years before the disease is diagnosed. Also, while they did try to correct for smoking status using statistical models, the BMI-mortality data shows very clearly that this isn't enough: to eliminate the smoking-leanness artifact, you have to do an analysis where you exclude smokers altogether (see the link above).

 

BMI is also just a lousy metric, as I think I pointed out in the link above, because it can't tell the difference between a person with a high BMI but is lean and has a lot of muscle (and who is therefore lean and generally metabolically pretty healthy) vs. one who has high BMI due to nothing but fat — or a low-BMI person who is all bone and muscle vs. one with no muscle at all and significant "hidden" visceral fat. This study is interesting in this regard, as it (a) has thirty-six years of followup , so that it avoids the question of weight loss in the preclinical years leading up to Alzheimer's onset (whereas the study on which the press report you saw only has nine years of followup), and it finds that even people whose low BMI suggests that they are "slim" may have central obesity that puts them at risk for dementia:

 

 

A longitudinal analysis was conducted of 6,583 members of Kaiser Permanente of Northern California who had their sagittal abdominal diameter (SAD) measured in 1964 to 1973. Diagnoses of dementia were from medical records an average of 36 years later, ... Cox proportional hazard models adjusted for age, sex, race, education, marital status, diabetes, hypertension, hyperlipidemia, stroke, heart disease, and medical utilization were conducted.
RESULTS:

... Compared with those in the lowest quintile of SAD, those in the highest had nearly a threefold increased risk of dementia (hazard ratio, 2.72; 95% CI, 2.33-3.33), and this was only mildly attenuated after adding body mass index (BMI) to the model (hazard ratio, 1.92; 95% CI, 1.58-2.35). Those with high SAD (>25 cm) and normal BMI had an increased risk (hazard ratio, 1.89; 95% CI, 0.98-3.81) vs those with low SAD (<25 cm) and normal BMI (18.5-24.9 kg/m(2)), whereas those both obese (BMI >30 kg/m(2)) and with high SAD had the highest risk of dementia (HR, 3.60; 95% CI, 2.85-4.55).

 

Also, as Scott notes, this is one of many, many studies that find that over the long term, obesity is associated with higher risk of AD or dementia: see for example press reports here, here, herehere, and here.

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