Head size may modify the impact of white matter lesions on dementia.

We aimed to examine whether total intracranial volume (TICV), a marker of premorbid brain size, modified the impact of the apolipoprotein E (apoE) e4 phenotype and ischemic white matter lesions (WMLs) on odds for dementia. The study comprised a population-based sample of 104 demented and 135 nondemented 85-year-olds, and included physical and neuropsychiatric examinations, and head computerized tomography (CT). Dementia disorders were defined according to standard criteria. TICV and WMLs were rated on computerized tomography. Using the highest group as reference, the risk for dementia, Alzheimer's disease (AD), and vascular dementia (VaD) was increased in those with the smallest half, tertile, and quartile of TICV. Smaller TICV increased the odds of dementia, Alzheimer's disease, and vascular dementia in participants with WMLs. WMLs were not associated with increased odds of dementia in those with the largest TICV. The interaction term WMLs*TICV was also significant. TICV did not modify the odds of dementia in those with the apolipoprotein e4 phenotype. Our results suggest that the impact of brain pathology on the risk of dementia is modified by premorbid brain size.