Diffusion Tensor MRI Structural Connectivity and PET Amyloid Burden in Preclinical Autosomal Dominant Alzheimer Disease: The DIAN Cohort

the Dominantly Inherited Alzheimer Network

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Background: Pathologic evidence of Alzheimer disease (AD) is detectable years before onset of clinical symptoms. Imaging-based identification of structural changes of the brain in people at genetic risk for early-onset AD may provide insights into how genes influence the pathologic cascade that leads to dementia. Purpose: To assess structural connectivity differences in cortical networks between cognitively normal autosomal dominant Alzheimer disease (ADAD) mutation carriers versus noncarriers and to determine the cross-sectional relationship of structural connectivity and cortical amyloid burden with estimated years to symptom onset (EYO) of dementia in carriers. Materials and Methods: In this exploratory analysis of a prospective trial, all participants enrolled in the Dominantly Inherited Alzheimer Network between January 2009 and July 2014 who had normal cognition at baseline, T1-weighted MRI scans, and diffusion tensor imaging (DTI) were analyzed. Amyloid PET imaging using Pittsburgh compound B was also analyzed for mutation carriers. Areas of the cerebral cortex were parcellated into three cortical networks: the default mode network, frontoparietal control network, and ventral attention network. The structural connectivity of the three networks was calculated from DTI. General linear models were used to examine differences in structural connectivity between mutation carriers and noncarriers and the relationship between structural connectivity, amyloid burden, and EYO in mutation carriers. Correlation network analysis was performed to identify clusters of related clinical and imaging markers. Results: There were 30 mutation carriers (mean age ± standard deviation, 34 years ± 10; 17 women) and 38 noncarriers (mean age, 37 years ± 10; 20 women). There was lower structural connectivity in the frontoparietal control network in mutation carriers compared with noncarriers (estimated effect of mutation-positive status, 20.0266; P = .04). Among mutation carriers, there was a correlation between EYO and white matter structural connectivity in the frontoparietal control network (estimated effect of EYO, 20.0015, P = .01). There was no significant relationship between cortical global amyloid burden and EYO among mutation carriers (P > .05). Conclusion: White matter structural connectivity was lower in autosomal dominant Alzheimer disease mutation carriers compared with noncarriers and correlated with estimated years to symptom onset.

Original languageEnglish
Pages (from-to)143-150
Number of pages8
JournalRadiology
Volume302
Issue number1
DOIs
StatePublished - Jan 2022

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