Cortical and Hippocampal Atrophy in Patients with Autosomal Dominant Familial Alzheimer’s Disease

Mary S. Easton Center for Alzheimer's Disease Research, Department of Neurology, UCLA School of Medicine, Los Angeles, Calif., USA.
Dementia and Geriatric Cognitive Disorders (Impact Factor: 3.55). 09/2011; 32(2):118-25. DOI: 10.1159/000330471
Source: PubMed


Both familial and sporadic Alzheimer's disease (AD) result in progressive cortical and subcortical atrophy. Familial autosomal dominant AD (FAD) allows us to study AD brain changes presymptomatically.
33 subjects at risk for FAD (25 for PSEN1 and 8 for APP mutations; 22 mutation carriers and 11 controls) and 3 demented PSEN1 mutation carriers underwent T(1)-weighted MPRAGE 1.5T MRI. Using the hippocampal radial distance and cortical pattern matching techniques, we investigated the effects of carrier status and dementia diagnosis on cortical and hippocampal atrophy. All analyses were corrected for age and relative age (years to median age of disease onset in the family).
The dementia cases had pronounced cortical atrophy in the lateral and medial parietal, posterior cingulate and frontal cortices and hippocampal atrophy bilaterally relative to both nondemented carriers and controls. Nondemented carriers did not show significant cortical thinning or hippocampal atrophy relative to controls.
FAD is associated with thinning of the posterior association and frontal cortices and hippocampal atrophy. Larger sample sizes may be necessary to reliably identify cortical atrophy in presymptomatic carriers.

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    • "Gray matter regional volume loss and decreases in magnetization transfer ratio have also been reported in mildly symptomatic carriers [69]. Additionally, it has been well established that in early onset AD, hippocampus may be not always involved as in the typical form and that frontoparietal areas showed greater atrophy in monogenic forms compared with sporadic late onset cases [68, 70, 71]. APP mutations seem to be more associated with hippocampal atrophy, whereas PSEN1 mutation carriers had more general neocortical involvement and a prominent frontotemporal atrophy [68, 72]. "
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