The protective role of brain size in Alzheimer's disease

Evaluation of: Perneczky R, Wagenpfeil S, Lunetta KL et al. Head circumference, atrophy, and cognition: implications for brain reserve in Alzheimer disease. Neurology 75, 137-142 (2010). The brain reserve hypothesis suggests that larger brain size is associated with a greater ability to tolerate pathological damage before showing any cognitive decline. This theory has been used to explain why many patients with Alzheimer's disease pathology are cognitively normal before death. However, the literature concerning the brain reserve hypothesis is mixed with evidence both for and against this theory. Perneczky and colleagues tested the theory by assessing whether premorbid brain size, measured using head circumference, alters the relationship between brain atrophy and cognitive decline in 270 Alzheimer's disease patients. They found that head circumference was associated with a reduced impact of atrophy on cognitive performance. Hence, for a given degree of atrophy, cognitive performance was better in patients with a larger head circumference. Therefore, these findings support the brain reserve hypothesis. This article will discuss the brain reserve concept and potential limitations and significance of this study.