Year: 2013
Type: article
Study design: Observational Study
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.
Source: Neurology
Authors: David M. Cash, Gerard R. Ridgway, Yuying Liang, Natalie S. Ryan, Kirsi M. Kinnunen, Thomas Yeatman, Ian B. Malone, Tammie L.S. Benzinger, Clifford R. Jack, Paul M. Thompson, Bernardino F. Ghetti, Andrew J. Saykin, Colin L. Masters, John M. Ringman, Stephen P. Salloway, Peter R. Schofield, Reisa A. Sperling, Nigel J. Cairns, Daniel S. Marcus, Chengjie Xiong, Randall J. Bateman, John C. Morris, Martin N. Rossor, Sébastien Ourselin, Nick C. Fox
Institutions: Brigham and Women's Hospital, Mayo Clinic, Mental Health Research Institute, University of California, Los Angeles, Wellcome Centre for Human Neuroimaging, The University of Melbourne, Washington University in St. Louis, Butler Hospital, Indiana University School of Medicine, UCL Queen Square Institute of Neurology, University College London, Indiana University, Neuroscience Research Australia
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Awards: Indiana Alzheimer Disease Center, NIHR Senior Investigator Award, Core support for the Wellcome Trust Centre for Neuroimaging., G666308703, Alzheimer's Disease Research Center, NINDS Center Core for Brain Imaging, Healthy Aging and Senile Dementia, Dominantly Inherited Alzheimer Network, NIHR Senior Investigator Award, Antecedent Biomarkers for Alzheimer Disease: The Adult Children Study
OpenAlex ID: W2163958074