Research ReportIntracranial volume and dementia: Some evidence in support of the cerebral reserve hypothesis

The brain reserve hypothesis has been posited as being one important mediating factor for developing dementia, especially Alzheimer's disease (AD). Evidence for this hypothesis is mixed though different methodologies have made these findings difficult to interpret. We examined imaging data from a large cohort (N = 194) of mixed dementia patients and controls, 65 years old and older from the Cache County, Utah Study of Memory and Aging for evidence of the brain reserve hypothesis using total intracranial volume (TICV) as a quantitative measure of pre-morbid brain size and a vicarious indicator of reserve. A broader spectrum of non-demented elderly control subjects from previous studies was also included for comparison (N = 423). In addition, non-parametric Classification and Regression Tree (CART) analyses were performed to model group heterogeneity and identify any subgroups of patients where TICV might be an important predictor of dementia. Parametrically, no main effect was found for TICV when predicting a dementia diagnosis; however, the CART analysis did reveal important TICV subgroups, including a sex differential wherein ε4 APOE allele presence in males and low TICV predicted AD classification. TICV, APOE, and other potential mediator/moderator variables are discussed in the context of the brain reserve hypothesis.

Research Highlights► There are a subset of patients for which total intracranial volume (TICV) appears to have an impact of predicting dementia diagnosis when examining data in a non-parametric fashion. ► There were no significant main effects for TICV when comparing dementia patients and healthy controls (parametric testing). ► APOE genotype appears to be more relevant for males with a smaller TICV when predicting dementia diagnosis.