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Neurology. 2013 Oct 15;81(16):1425-33. doi: 10.1212/WNL.0b013e3182a841c6. Epub 2013 Sep 18.

The pattern of atrophy in familial Alzheimer disease: volumetric MRI results from the DIAN study.

Author information

1
From the Dementia Research Centre (D.M.C., Y.L., N.S.R., K.M.K., T.Y., I.B.M., M.N.R., S.O., N.C.F.) and Wellcome Trust Centre for Neuroimaging (G.R.R.), UCL Institute of Neurology, London, UK; Washington University School of Medicine (T.L.S.B., N.J.C., D.S.M., C.X., R.J.B., J.C.M.), St. Louis, MO; Mayo Clinic (C.R.J.), Rochester, MN; Imaging Genetics Center (P.M.T.), Laboratory of Neuroimaging, Department of Neurology & Psychiatry, UCLA School of Medicine, Los Angeles, CA; Indiana University School of Medicine (B.F.G., A.J.S.), Indianapolis; Mental Health Research Institute (C.L.M.), The University Of Melbourne, Victoria, Australia; Mary S. Easton Center for Alzheimer's Disease (J.M.R.), UCLA Department of Neurology, Los Angeles, CA; Butler Hospital (S.P.S.), Providence, RI; Neuroscience Research Australia (P.R.S.), Sydney; and the Center for Alzheimer Research and Treatment (R.A.S.), Brigham and Women's Hospital, Cambridge, MA.

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.

PMID:
24049139
PMCID:
PMC3806583
DOI:
10.1212/WNL.0b013e3182a841c6
[Indexed for MEDLINE]
Free PMC Article

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