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Most studies aiming to make this distinction focused on older adults only and on a priori anatomical regions. Drawing on a large, multi-cohort dataset ranging from young adults (n = 468; age range 18\u201335 years), to older adults with intact cognition (n = 431; age range 55\u201390 years) and with Alzheimer\u2019s disease (n = 50 with late mild cognitive impairment and 71 with Alzheimer\u2019s dementia, age range 56\u201388 years), we investigated grey matter organization and volume differences in ageing and Alzheimer\u2019s disease. Using independent component analysis on all participants\u2019 structural MRI, we first derived morphometric networks and extracted grey matter volume in each network. We also derived a measure of whole-brain grey matter pattern organization by correlating grey matter volume in all networks across all participants from the same cohort. We used logistic regressions and receiver operating characteristic analyses to evaluate how well grey matter volume in each network and whole-brain pattern could discriminate between ageing and Alzheimer\u2019s disease. Because increased heterogeneity is often reported as one of the main features characterizing brain ageing, we also evaluated interindividual heterogeneity within morphometric networks and across the whole-brain organization in ageing and Alzheimer\u2019s disease. Finally, to investigate the clinical validity of the different grey matter features, we evaluated whether grey matter volume or whole-brain pattern was related to clinical progression in cognitively normal older adults. Ageing and Alzheimer\u2019s disease contributed additive effects on grey matter volume in nearly all networks, except frontal lobe networks, where differences in grey matter were more specific to ageing. While no networks specifically discriminated Alzheimer\u2019s disease from ageing, heterogeneity in grey matter volumes across morphometric networks and in the whole-brain grey matter pattern characterized individuals with cognitive impairments. Preservation of the whole-brain grey matter pattern was also related to lower risk of developing cognitive impairment, more so than grey matter volume. These results suggest both ageing and Alzheimer\u2019s disease involve widespread atrophy, but that the clinical expression of Alzheimer\u2019s disease is uniquely associated with disruption of morphometric organization.<\/jats:p>","DOI":"10.1093\/brain\/awz414","type":"journal-article","created":{"date-parts":[[2019,12,20]],"date-time":"2019-12-20T20:11:18Z","timestamp":1576872678000},"page":"635-649","source":"Crossref","is-referenced-by-count":59,"title":["Morphometric network differences in ageing versus Alzheimer\u2019s disease dementia"],"prefix":"10.1093","volume":"143","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5218-3337","authenticated-orcid":false,"given":"Alexa","family":"Pichet Binette","sequence":"first","affiliation":[{"name":"Department of Psychiatry, Faculty of Medicine, McGill University, Montreal, Qc, H3A 1Y2, Canada"},{"name":"Douglas Mental Health University Institute, Montreal, Qc, H4H 1R3, 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Institute, Montreal, Qc, H4H 1R3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D Louis","family":"Collins","sequence":"additional","affiliation":[{"name":"McConnell Brain Imaging Center, Montreal Neurological Institute, Montreal, Qc, H3A 2B4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judes","family":"Poirier","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Faculty of Medicine, McGill University, Montreal, Qc, H3A 1Y2, Canada"},{"name":"Douglas Mental Health University Institute, Montreal, Qc, H4H 1R3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C S","family":"Breitner","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Faculty of Medicine, McGill University, Montreal, Qc, H3A 1Y2, Canada"},{"name":"Douglas Mental Health University Institute, Montreal, Qc, H4H 1R3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvia","family":"Villeneuve","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Faculty of Medicine, McGill University, Montreal, Qc, H3A 1Y2, Canada"},{"name":"Douglas Mental Health University Institute, Montreal, Qc, H4H 1R3, Canada"},{"name":"McConnell Brain Imaging Center, Montreal Neurological Institute, Montreal, Qc, H3A 2B4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8681-3154","authenticated-orcid":false,"given":"Etienne","family":"Vachon-Presseau","sequence":"additional","affiliation":[{"name":"Department of Anesthesia, Faculty of Medicine, McGill University, Montreal, Qc, H3A 1G1, Canada"},{"name":"Faculty of Dentistry, McGill University, Montreal, Qc, H3A 1G1, Canada"},{"name":"Alan Edwards Centre for Research on Pain (AECRP), McGill University, Montreal, Qc, H3A 1G1, 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