Frontal-hippocampal double dissociation between normal aging and Alzheimer's disease.
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.
Head
Denise
D
Howard Hughes Medical Institute, One Brookings Drive, Department of Psychology, Washington University, St Louis, MO 63130, USA. dhead@artsci.wustl.edu
Snyder
Abraham Z
AZ
Girton
Laura E
LE
Morris
John C
JC
Buckner
Randy L
RL
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