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We used a sample of 72 people across the age span, enriched for the APOE4 genotype to reveal vulnerable networks associated with a composite AD risk factor including age, genotype, and sex. Sparse canonical correlation analysis (CCA) revealed a high weight associated with genotype, and subgraphs involving the cuneus, temporal, cingulate cortices, and cerebellum. Adding cognitive metrics to the risk factor revealed the highest cumulative degree of connectivity for the pericalcarine cortex, insula, banks of the superior sulcus, and the cerebellum. To enable scaling up our approach, we extended tensor network principal component analysis, introducing CCA components. We developed sparse regression predictive models with errors of 17% for genotype, 24% for family risk factor for AD, and 5 years for age. Age prediction in groups including cognitively impaired subjects revealed regions not found using only normal subjects, i.e. middle and transverse temporal, paracentral and superior banks of temporal sulcus, as well as the amygdala and parahippocampal gyrus. These modeling approaches represent stepping stones towards single subject prediction.<\/jats:p>","DOI":"10.1093\/cercor\/bhac419","type":"journal-article","created":{"date-parts":[[2022,9,29]],"date-time":"2022-09-29T09:24:08Z","timestamp":1664443448000},"page":"5307-5322","source":"Crossref","is-referenced-by-count":15,"title":["Identifying vulnerable brain networks associated with Alzheimer\u2019s disease risk"],"prefix":"10.1093","volume":"33","author":[{"given":"Ali","family":"Mahzarnia","sequence":"first","affiliation":[{"name":"Radiology Department, Duke University Medical School , Durham, 27710 NC , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques A","family":"Stout","sequence":"additional","affiliation":[{"name":"Brain Imaging and Analysis Center, Duke University Medical School , Durham, 27710 NC , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert 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