Though the characteristic dementia and brain lesions of Alzheimer’s were first described a century ago, the disease only recently captured the attention of the research community. In 1975, when the NIH was supporting hundreds of research projects on atherosclerosis and cholesterol metabolism, it was funding fewer than a dozen on Alzheimer’s and what was then called senile dementia. This number rose gradually through the end of the 1970s. Between 1982 and 1985, the number of Alzheimer’s-related research projects funded by the NIH quintupled.

It took another decade for researchers to begin reporting that heart disease and Alzheimer’s seem to share risk factors: hypertension, atherosclerosis, and smoking are all associated with an increased risk of Alzheimer’s, as is the inheritance of a particular variant of a gene called apolipoprotein E4 (apo E4) that also increases the risk of cardiovascular disease.*59 This in turn led to the notion that what’s good for the heart is good for the brain, but that, of course, depends on our understanding of what exactly is good for the heart. Because Alzheimer’s researchers, like diabetologists, assume that Keys’s fat-cholesterol hypothesis is supported by compelling evidence, they will often suggest that cholesterol and saturated fat play a role in Alzheimer’s as well. But if coronary heart disease is mostly a product of the physiological abnormalities of metabolic syndrome, as the evidence suggests, then this implicates insulin, blood sugar, and refined carbohydrates instead, a conclusion supported by several lines of research that began to converge in the last decade.

A handful of studies have suggested that Alzheimer’s is another disease of civilization, with a pattern of distribution similar, if not identical, to heart disease, diabetes, and obesity. Japanese Americans, for instance, develop a pattern of dementia—the ratio of Alzheimer’s dementia to the stroke-related condition known as vascular dementia—that is typically American; when Japanese immigrate to the United States, their likelihood of developing Alzheimer’s disease increases considerably, while their risk of developing vascular dementia decreases. The incidence of Alzheimer’s dementia in African Americans, according to research published in JAMA in 2001, is twice that of rural Africans, and they are three times as likely to suffer vascular dementia, again suggesting that dietary or lifestyle factors play a role in both dementias.

Studies in large populations—6,000 elderly subjects in Rotterdam, 1,500 in Minnesota, 1,300 in Manhattan, 800 Catholic nuns, priests, and brothers in the American Midwest, and 2,500 Japanese Americans in Honolulu—have suggested that Type 2 diabetics have roughly twice as much risk of contracting Alzheimer’s disease as nondiabetics. Diabetics on insulin therapy, according to the Rotterdam study, had a fourfold increase in risk. Hyperinsulinemia and metabolic syndrome are also associated with an increased risk of Alzheimer’s disease. And so one interpretation of these results, as the Rotterdam investigators noted in 1999, is that “direct or indirect effects of insulin could contribute to the risk of dementia.”