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Publication Detail
The pattern of atrophy in familial Alzheimer disease: volumetric MRI results from the DIAN study.
  • Publication Type:
    Journal article
  • Publication Sub Type:
    Comparative Study
  • Authors:
    Cash DM, Ridgway GR, Liang Y, Ryan NS, Kinnunen KM, Yeatman T, Malone IB, Benzinger TLS, Jack CR, Thompson PM, Ghetti BF, Saykin AJ, Masters CL, Ringman JM, Salloway SP, Schofield PR, Sperling RA, Cairns NJ, Marcus DS, Xiong C, Bateman RJ, Morris JC, Rossor MN, Ourselin S, Fox NC, Dominantly Inherited Alzheimer Network (DIAN)
  • Publication date:
    15/10/2013
  • Pagination:
    1425, 1433
  • Journal:
    Neurology
  • Volume:
    81
  • Issue:
    16
  • Status:
    Published
  • Country:
    United States
  • PII:
    WNL.0b013e3182a841c6
  • Language:
    eng
  • Keywords:
    Adult, Age of Onset, Alzheimer Disease, Atrophy, Cerebral Cortex, Cerebrum, Cohort Studies, Female, Heterozygote, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Prodromal Symptoms, Prognosis, Young Adult
Abstract
OBJECTIVE: To assess regional patterns of gray and white matter atrophy in familial Alzheimer disease (FAD) mutation carriers. METHODS: A total of 192 participants with volumetric T1-weighted MRI, genotyping, and clinical diagnosis were available from the Dominantly Inherited Alzheimer Network. Of these, 69 were presymptomatic mutation carriers, 50 were symptomatic carriers (31 with Clinical Dementia Rating [CDR] = 0.5, 19 with CDR > 0.5), and 73 were noncarriers from the same families. Voxel-based morphometry was used to identify cross-sectional group differences in gray matter and white matter volume. RESULTS: Significant differences in gray matter (p < 0.05, family-wise error-corrected) were observed between noncarriers and mildly symptomatic (CDR = 0.5) carriers in the thalamus and putamen, as well as in the temporal lobe, precuneus, and cingulate gyrus; the same pattern, but with more extensive changes, was seen in those with CDR > 0.5. Significant white matter differences between noncarriers and symptomatic carriers were observed in the cingulum and fornix; these form input and output connections to the medial temporal lobe, cingulate, and precuneus. No differences between noncarriers and presymptomatic carriers survived correction for multiple comparisons, but there was a trend for decreased gray matter in the thalamus for carriers closer to their estimated age at onset. There were no significant increases of gray or white matter in asymptomatic or symptomatic carriers compared to noncarriers. CONCLUSIONS: Atrophy in FAD is observed early, both in areas commonly associated with sporadic Alzheimer disease and also in the putamen and thalamus, 2 regions associated with early amyloid deposition in FAD mutation carriers.
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Division of Psychiatry
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Dept of Med Phys & Biomedical Eng
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