title: Intracranial volume and dementia: some evidence in support of the cerebral reserve hypothesis.
abstract: 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, 65years 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.
authors.affiliation: Center for Neurological Imaging, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. dtate1@partners.org
authors.forename: D F
authors.initials: DF
authors.lastname: Tate
authors.forename: E S
authors.initials: ES
authors.lastname: Neeley
authors.forename: M C
authors.initials: MC
authors.lastname: Norton
authors.forename: J T
authors.initials: JT
authors.lastname: Tschanz
authors.forename: M J
authors.initials: MJ
authors.lastname: Miller
authors.forename: L
authors.initials: L
authors.lastname: Wolfson
authors.forename: C
authors.initials: C
authors.lastname: Hulette
authors.forename: C
authors.initials: C
authors.lastname: Leslie
authors.forename: K A
authors.initials: KA
authors.lastname: Welsh-Bohmer
authors.forename: B
authors.initials: B
authors.lastname: Plassman
authors.forename: Erin D
authors.initials: ED
authors.lastname: Bigler
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D053327:Apolipoprotein E4 / Q000235:genetics; D054022:Cerebrum / Q000473:pathology*; D058245:Cognitive Reserve / Q000502:physiology*; D015331:Cohort Studies; D003704:Dementia / Q000235:genetics / Q000473:pathology* / Q000523:psychology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009929:Organ Size; D012727:Sex Characteristics; D055815:Young Adult
chemical_list: D053327:Apolipoprotein E4