title: Frontal-hippocampal double dissociation between normal aging and Alzheimer's disease.
abstract: Controversy persists regarding whether Alzheimer's disease (AD) is a distinct entity or instead exists on a continuum with nondemented aging. To explore this issue, volumetric analyses of callosal and hippocampal regions were performed on 150 participants aged 18-93 years. Group-level analyses revealed that nondemented age-related differences were greater in anterior than posterior callosal regions and were not augmented by early-stage AD. In contrast, early-stage AD was associated with substantial reduction in hippocampal volume. Examination of the 100 older adults using regression analyses demonstrated age-associated differences in callosal volume that were similar in demented and nondemented individuals. Early-stage AD was again characterized by a marked reduction in hippocampal volume while age alone induced only mild differences in hippocampal volume. As a final analysis, the formal double dissociation was confirmed by comparing the effects of age directly against the effects of dementia. These results suggest a multiple-component model of aging. One process, associated with AD, manifests early and prominently in the medial temporal lobe. A separate process, ubiquitous in aging, affects brain white matter with an anterior-to-posterior gradient and may underlie the executive difficulties common in aging.
authors.affiliation: Howard Hughes Medical Institute, One Brookings Drive, Department of Psychology, Washington University, St Louis, MO 63130, USA. dhead@artsci.wustl.edu
authors.forename: Denise
authors.initials: D
authors.lastname: Head
authors.forename: Abraham Z
authors.initials: AZ
authors.lastname: Snyder
authors.forename: Laura E
authors.initials: LE
authors.lastname: Girton
authors.forename: John C
authors.initials: JC
authors.lastname: Morris
authors.forename: Randy L
authors.initials: RL
authors.lastname: Buckner
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology*; D000544:Alzheimer Disease / Q000473:pathology*; D015331:Cohort Studies; D003337:Corpus Callosum / Q000166:cytology / Q000473:pathology*; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D013702:Temporal Lobe / Q000166:cytology / Q000473:pathology