Year: 2025
Type: article
Study design: Observational Study
Abstract: Cognitive and behavioral deficits in Alzheimer's disease (AD) and frontotemporal dementia (FTD) result from brain atrophy and altered functional connectivity. However, it is unclear how atrophy relates to functional connectivity disruptions across dementia subtypes and stages. We addressed this question using structural and functional MRI from 221 patients with AD (n=82), behavioral variant FTD (n=41), corticobasal syndrome (n=27), nonfluent (n=34) and semantic (n=37) variant primary progressive aphasia, and 100 cognitively normal individuals. Using partial least squares regression, we identified three principal structure-function components. The first component showed overall atrophy correlating with primary cortical hypo-connectivity and subcortical/association cortical hyper-connectivity. Components two and three linked focal syndrome-specific atrophy to peri-lesional hypo-connectivity and distal hyper-connectivity. Structural and functional component scores predicted global and domain-specific cognitive deficits. Anatomically, functional connectivity changes reflected alterations in specific brain activity gradients. Eigenmode analysis identified temporal phase and amplitude collapse as an explanation for atrophy-driven functional connectivity changes.
Source: Nature Communications
Authors: Jesse A. Brown, Alex J. Lee, Kristen Fernhoff, Taylor Pistone, Lorenzo Pasquini, Amy B. Wise, Adam M. Staffaroni, Maria Luisa Mandelli, Suzee E. Lee, Adam L. Boxer, Katherine P. Rankin, Gil D. Rabinovici, Maria Luisa Gorno Tempini, Howard J. Rosen, Joel H. Kramer, Bruce L. Miller, William W. Seeley, Alzheimer’s Disease Neuroimaging Initiative (ADNI)
Institution: University of California, San Francisco
Language: English
Subfield: Cognitive Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
Funders: U.S. Department of Defense, U.S. Department of Health and Human Services, Alzheimer's Association, Larry L. Hillblom Foundation, Bristol-Myers Squibb, Eli Lilly and Company, Pfizer, Biogen, University of Southern California, F. Hoffmann-La Roche, Meso Scale Diagnostics, Alzheimer's Disease Neuroimaging Initiative, BioClinica, Novartis Pharmaceuticals Corporation, Northern California Institute for Research and Education, Eisai, Servier, H. Lundbeck A/S, IXICO, National Institutes of Health, Genentech, Canadian Institutes of Health Research, National Institute on Aging, National Institute on Deafness and Other Communication Disorders
Awards: G1012222616, G1298807586, G1554142629, G1593117279, G1650819308, Frontotemporal Dementia: Genes, Images and Emotions, G1880935189, G1888650583, Defining trajectories of dynamic biomarkers for C9ORF72 repeat expansion carriers, Alzheimer's Disease Neuroimaging Initiative, G2100670906, G2152643862, G2189010064, G2340207221, G2423387114, G2471646051, G2522063444, G2835601961, Patient-tailored network prediction of neurodegenerative disease progression, G29951154, G3087761170, G3131374986, New Approaches to Dementia Heterogeneity, G3216574877, G3553156159, G3710456697, G3752451908, G3870774570, G3908963977, G3966393351, G4119534169, Primary Progressive Aphasia: Cognition, Anatomy and Progression, G43180419, G4475667458, G4501223628, G4800177743, G5207404921, G5209990037, G528601746, G5365730499, EFFECTS OF TRAUMATIC BRAIN INJURY (TBI) AND POST TRAUMATIC STRESS DISORDER (PTSD) ON ALZHEIMER'S DISEASE (AD) IN VETERANS USING IMAGING AND BIOMARKERS IN THE AD NEUROIMAGING INITIATIVE (ADNI)", G5654639750, G5707719899, G5740349702, G5850682332, G603598372, G613619302, G6173816828, G6210868510, G6371410416, G6412110892, G6447063303, G6719828067, G6792506723, G6899163935, G6948409098, G7093851537, G7140046214, G72415811, G7298697282, G764699806, G7799614282, G781725486, G7822125570, G8228018387, G8281378126, G839208290, Dynamic neural systems underlying socioemotional function, The Four Repeat Tauopathy Neuroimaging Initiative, G8852128998, G8895907669, G8897063270, G8957659042, G9000018678, G9000029343, G9000039018, G9000062124, G9000122335, G9000147287, G9000173587, ARTFL LEFFTDS Longitudinal Frontotemporal Lobar Degeneration, Cycle 2 (ALLFTD2), Training program in the neurology of language and neurodegenerative aphasias, Primary Progressive Aphasia: Cognition, Anatomy and Progression
OpenAlex ID: W4416470705