Serum folate and the severity of atrophy of the neocortex in Alzheimer disease: findings from the Nun Study

Background: Previous studies suggested that low concentrations of folate in the blood are related to poor cognitive function, dementia, and Alzheimer disease-related neurodegeneration of the brain. Objective: Our aim was to determine whether serum folate is inversely associated with the severity of atrophy of the neocortex. Design: Nutrients, lipoproteins, and nutritional markers were measured in the blood of 30 participants in the Nun Study from one convent who later died when they were 78-101 y old ([bar]x: 91 y). At autopsy, several neuropathologic indicators of Alzheimer disease were determined, including the degree of atrophy of 3 lobes of the neocortex (frontal, temporal, and parietal) and the number of neocortical Alzheimer disease lesions (ie, senile plaques and neurofibrillary tangles) as assessed by a neuropathologist. Results: The correlation between serum folate and the severity of atrophy of the neocortex was -0.40 (P = 0.03). Among a subset of 15 participants with significant numbers of Alzheimer disease lesions in the neocortex, the correlation between folate and atrophy was -0.80 (P = 0.0006). Atrophy may be specific to low folate because none of the 18 other nutrients, lipoproteins, or nutritional markers measured in the blood had significant negative correlations with atrophy. Conclusions: Among elderly Catholic sisters who lived in one convent, ate from the same kitchen, and were highly comparable for a wide range of environmental and lifestyle factors, low serum folate was strongly associated with atrophy of the cerebral cortex. Definitive evidence for this relation and its temporal sequence awaits the findings of other studies. Am J Clin Nutr 2000;71:993-8. KEY WORDS Folate, folic acid, diet, nutrition, dementia, neocortex, Alzheimer disease, women, Nun Study