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Updated: Aug 22, 2026

The Double-H Maze: A Robust Behavioral Test for Learning and Memory in Rodents
Published on: July 8, 2015
Frontal-hippocampal double dissociation between normal aging and Alzheimer's disease
Denise Head1, Abraham Z Snyder, Laura E Girton
1Howard Hughes Medical Institute, One Brookings Drive, Department of Psychology, Washington University, St Louis, MO 63130, USA. dhead@artsci.wustl.edu
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.
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