Cerebral Cortex Advance Access originally published online on September 15, 2004
Cerebral Cortex 2005 15(6):732-739; doi:10.1093/cercor/bhh174
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Cerebral Cortex V 15 N 6 © Oxford University Press 2004; all rights reserved
Frontal-Hippocampal Double Dissociation Between Normal Aging and Alzheimer's Disease
1 Howard Hughes Medical Institute, One Brookings Drive, St Louis, MO 63130, USA, 2 Department of Psychology, Washington University, St Louis, MO 63130, USA, 3 Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, MO 63110, USA, 4 Department of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA, 5 Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO 63110, USA and 6 Department of Anatomy and Neurobiology, Washington University School of Medicine, St Louis, MO 63110, USA
Address correspondence to Denise Head, HHMI at Washington University, Psychology Department Campus Box 1125, One Brookings Drive, St Louis, MO 63130, USA. email: dhead{at}artsci.wustl.edu.
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.
Key Words: corpus callosum • dementia • MCI • MRI • white matter
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