Abstract
BACKGROUND: Clinical and epidemiologic studies suggest that patients with Alzheimer disease (AD) with larger head circumference have better cognitive performance at the same level of brain pathology than subjects with smaller head circumference. METHODS: A total of 270 patients with AD participating in the Multi-Institutional Research in Alzheimer's Genetic Epidemiology (MIRAGE) study underwent cognitive testing, APOE genotyping, and MRI of the brain in a cross-sectional study. Linear regression analysis was used to examine the association between cerebral atrophy, as a proxy for AD pathology, and level of cognitive function, adjusting for age, duration of AD symptoms, gender, head circumference, APOE genotype, diabetes mellitus, hypertension, major depression, and ethnicity. An interaction term between atrophy and head circumference was introduced to explore if head circumference modified the association between cerebral atrophy and cognition. RESULTS: There was a significant inverse association between atrophy and cognitive function, and a significant interaction between atrophy and head circumference. With greater levels of atrophy, cognition was higher for individuals with greater head circumference. CONCLUSION: This study suggests that larger head circumference is associated with less cognitive impairment in the face of cerebral atrophy. This finding supports the notion that head circumference (and presumably brain size) offers protection against AD symptoms through enhanced brain reserve.