Muller M, Tang MX, Schupf N, Manly JJ, Mayeux R, Luchsinger JA.
Metabolic syndrome and dementia risk in a multiethnic elderly cohort.
Dement Geriatr Cogn Disord. 2007;24(3):185-92.
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An accumulation of "evidence" suggests that several factors may be associated with an increased incidence/prevalence of AD. I use the term "evidence" loosely, in a colloquial sense, because the observations have not been generated in a systematic manner in order to prove a hypothesis, nor have they been subjected to any system which weighs their value. The loose evidence includes the fact that overfed cells and animals suffer many metabolic consequences that lead to shorter lifespans; the observation that brain cells do not metabolize glucose well in AD brains; epidemiologic studies linking metabolic syndrome to cognitive decline in older individuals; epidemiologic studies linking diabetes mellitus to a greater risk for developing AD. At best, this list of factors is circumstantial and impressionistic. Further, there are counter-examples for most of these observations in the literature. In order to move the field ahead, we have to introduce more precise definitions, prospective studies, and clearly defined outcomes. The study by Muller et al. comes from a group that has developed careful methodologies and worked with the same population-based sample over a period of years. Their definitions attempt to differentiate some of the components of AD risk related to overfeeding/under-metabolizing, and their conclusion that these components should be studied separately is well supported.
More challenging still is the need to introduce another dimension into these discussions and analyses: the dimension of time. It is entirely possible that any conclusions we draw with regard to elderly patients observed for a few years are irrelevant to middle-aged individuals, or to their risk for developing clinically silent AD brain changes. These authors were careful to qualify their findings with respect to the age of the population under study.
Roses and Saunders. Alzheimer's & Dementia. 2006;2:59-70.
Yaffe K, Kanaya A, Lindquist K, Simonsick EM, Harris T, Shorr RI, Tylavsky FA, Newman AB.
The metabolic syndrome, inflammation, and risk of cognitive decline.
JAMA. 2004 Nov 10;292(18):2237-42.
Luchsinger JA, Tang MX, Shea S, Mayeux R.
Hyperinsulinemia and risk of Alzheimer disease.
Neurology. 2004 Oct 12;63(7):1187-92.
Arvanitakis Z, Wilson RS, Bienias JL, Evans DA, Bennett DA.
Diabetes mellitus and risk of Alzheimer disease and decline in cognitive function.
Arch Neurol. 2004 May 1;61(5):661-6.
Xu WL, Qiu CX, Wahlin A, Winblad B, Fratiglioni L.
Diabetes mellitus and risk of dementia in the Kungsholmen project: a 6-year follow-up study.
Neurology. 2004 Oct 12;63(7):1181-6.
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