Frontal-hippocampal double dissociation between normal aging and Alzheimer's disease

Cereb Cortex. 2005 Jun;15(6):732-9. doi: 10.1093/cercor/bhh174. Epub 2004 Sep 15.

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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Aging / pathology*
  • Alzheimer Disease / pathology*
  • Cohort Studies
  • Corpus Callosum / cytology
  • Corpus Callosum / pathology*
  • Female
  • Hippocampus / cytology
  • Hippocampus / pathology*
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Temporal Lobe / cytology
  • Temporal Lobe / pathology