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To test whether clinicoanatomic heterogeneity in AD is driven by the involvement of specific networks, network connectivity was assessed in healthy subjects by seeding regions commonly and specifically atrophied in three clinical AD variants: early-onset AD (age at onset, &lt;65 y; memory and executive deficits), logopenic variant primary progressive aphasia (language deficits), and posterior cortical atrophy (visuospatial deficits). Four-millimeter seed regions of interest were used to obtain intrinsic connectivity maps in 131 healthy controls (age, 65.5 \u00b1 3.5 y). Atrophy patterns in independent cohorts of AD variant patients and their correspondence to connectivity networks in controls were also assessed. The connectivity maps of commonly atrophied regions of interest support posterior DMN and precuneus network involvement across AD variants, whereas seeding regions specifically atrophied in each AD variant revealed distinct, syndrome-specific connectivity patterns. Goodness-of-fit analysis of each connectivity map with network templates showed the highest correspondence between the early-onset AD seed connectivity map and anterior salience and right executive-control networks, the logopenic aphasia seed connectivity map and the language network, and the posterior cortical atrophy seed connectivity map and the higher visual network. Connectivity maps derived from controls matched regions commonly and specifically atrophied in the patients. Our findings indicate that the posterior DMN and precuneus network are commonly affected in AD variants, whereas syndrome-specific neurodegenerative patterns are driven by the involvement of specific networks outside the DMN.<\/jats:p>","DOI":"10.1073\/pnas.1221536110","type":"journal-article","created":{"date-parts":[[2013,6,25]],"date-time":"2013-06-25T00:20:05Z","timestamp":1372119605000},"page":"11606-11611","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":115,"title":["Intrinsic connectivity networks in healthy subjects explain clinical variability in Alzheimer\u2019s disease"],"prefix":"10.1073","volume":"110","author":[{"given":"Manja","family":"Lehmann","sequence":"first","affiliation":[{"name":"Memory and Aging Center, Department of Neurology, University of California, San Francisco, CA 94158;"},{"name":"Helen Wills Neuroscience Institute, University of California, Berkeley, CA 94720;"},{"name":"Dementia Research Centre, Institute of Neurology, University College London, London WC1N 3BG, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cindee M.","family":"Madison","sequence":"additional","affiliation":[{"name":"Helen Wills Neuroscience Institute, University of California, Berkeley, CA 94720;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pia M.","family":"Ghosh","sequence":"additional","affiliation":[{"name":"Memory and Aging Center, Department of Neurology, University of California, San Francisco, CA 94158;"},{"name":"Helen Wills Neuroscience Institute, University of California, Berkeley, CA 94720;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William W.","family":"Seeley","sequence":"additional","affiliation":[{"name":"Memory and Aging Center, Department of Neurology, University of California, San Francisco, CA 94158;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Mormino","sequence":"additional","affiliation":[{"name":"Helen Wills Neuroscience Institute, University of California, Berkeley, CA 94720;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael D.","family":"Greicius","sequence":"additional","affiliation":[{"name":"Functional Imaging in Neuropsychiatric Disorders Laboratory, Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305; 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