Impaired default network functional connectivity in autosomal dominant Alzheimer disease.
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ABSTRACT: Objective
To investigate default mode network (DMN) functional connectivity MRI (fcMRI) in a large cross-sectional cohort of subjects from families harboring pathogenic presenilin-1 (PSEN1), presenilin-2 (PSEN2), and amyloid precursor protein (APP) mutations participating in the Dominantly Inherited Alzheimer Network.Methods
Eighty-three mutation carriers and 37 asymptomatic noncarriers from the same families underwent fMRI during resting state at 8 centers in the United States, United Kingdom, and Australia. Using group-independent component analysis, fcMRI was compared using mutation status and Clinical Dementia Rating to stratify groups, and related to each participant's estimated years from expected symptom onset (eYO).Results
We observed significantly decreased DMN fcMRI in mutation carriers with increasing Clinical Dementia Rating, most evident in the precuneus/posterior cingulate and parietal cortices (p < 0.001). Comparison of asymptomatic mutation carriers with noncarriers demonstrated decreased fcMRI in the precuneus/posterior cingulate (p = 0.014) and right parietal cortex (p = 0.0016). We observed a significant interaction between mutation carrier status and eYO, with decreases in DMN fcMRI observed as mutation carriers approached and surpassed their eYO.Conclusion
Functional disruption of the DMN occurs early in the course of autosomal dominant Alzheimer disease, beginning before clinically evident symptoms, and worsening with increased impairment. These findings suggest that DMN fcMRI may prove useful as a biomarker across a wide spectrum of disease, and support the feasibility of DMN fcMRI as a secondary endpoint in upcoming multicenter clinical trials in Alzheimer disease.
SUBMITTER: Chhatwal JP
PROVIDER: S-EPMC3776464 | biostudies-literature | 2013 Aug
REPOSITORIES: biostudies-literature
Publications
Impaired default network functional connectivity in autosomal dominant Alzheimer disease.
Chhatwal Jasmeer P JP Schultz Aaron P AP Johnson Keith K Benzinger Tammie L S TL Jack Clifford C Ances Beau M BM Sullivan Caroline A CA Salloway Stephen P SP Ringman John M JM Koeppe Robert A RA Marcus Daniel S DS Thompson Paul P Saykin Andrew J AJ Correia Stephen S Schofield Peter R PR Rowe Christopher C CC Fox Nick C NC Brickman Adam M AM Mayeux Richard R McDade Eric E Bateman Randall R Fagan Anne M AM Goate Allison M AM Xiong Chengjie C Buckles Virginia D VD Morris John C JC Sperling Reisa A RA
Neurology 20130724 8
<h4>Objective</h4>To investigate default mode network (DMN) functional connectivity MRI (fcMRI) in a large cross-sectional cohort of subjects from families harboring pathogenic presenilin-1 (PSEN1), presenilin-2 (PSEN2), and amyloid precursor protein (APP) mutations participating in the Dominantly Inherited Alzheimer Network.<h4>Methods</h4>Eighty-three mutation carriers and 37 asymptomatic noncarriers from the same families underwent fMRI during resting state at 8 centers in the United States, ...[more]
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