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Impaired default network functional connectivity in autosomal dominant Alzheimer disease
Open accessAbstract
OBJECTIVE: To investigate default mode network (DMN) functional connectivity MRI (fcMRI) in a large cross-sectional cohort of subjects from families harboring pathogenic presenilin-1 (PSEN1), presenilin-2 (PSEN2), and amyloid precursor protein (APP) mutations participating in the Dominantly Inherited Alzheimer Network. METHODS: Eighty-three mutation carriers and 37 asymptomatic noncarriers from the same families underwent fMRI during resting state at 8 centers in the United States, United Kingdom, and Australia. Using group-independent component analysis, fcMRI was compared using mutation status and Clinical Dementia Rating to stratify groups, and related to each participant's estimated years from expected symptom onset (eYO). RESULTS: We observed significantly decreased DMN fcMRI in mutation carriers with increasing Clinical Dementia Rating, most evident in the precuneus/posterior cingulate and parietal cortices (p < 0.001). Comparison of asymptomatic mutation carriers with noncarriers demonstrated decreased fcMRI in the precuneus/posterior cingulate (p = 0.014) and right parietal cortex (p = 0.0016). We observed a significant interaction between mutation carrier status and eYO, with decreases in DMN fcMRI observed as mutation carriers approached and surpassed their eYO. CONCLUSION: Functional disruption of the DMN occurs early in the course of autosomal dominant Alzheimer disease, beginning before clinically evident symptoms, and worsening with increased impairment. These findings suggest that DMN fcMRI may prove useful as a biomarker across a wide spectrum of disease, and support the feasibility of DMN fcMRI as a secondary endpoint in upcoming multicenter clinical trials in Alzheimer disease.
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“our findings support the possibility that callosal white matter degeneration contribute to functional disruption of functional networks such as the default mode network (Chhatwal et al., 2013; Mueller and Weiner, 2017; Taylor et al., 2017)”
From White matter diffusion alterations precede symptom onset in autosomal dominant Alzheimer’s disease (2018) · cites this paper as Chhatwal et al., 2013
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“a functional network showing reduced connectivity in early-stage Alzheimer’s disease (Sorg et al., 2007; Chhatwal et al., 2013)”
From White matter diffusion alterations precede symptom onset in autosomal dominant Alzheimer’s disease (2018) · cites this paper as Chhatwal et al., 2013
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Metadata
- Authors
- Chhatwal, J. P., Schultz, A. P., Johnson, K., Benzinger, T. L. S., Jack, C., Ances, B. M., Sullivan, C. A., Salloway, S. P., Ringman, J. M., Koeppe, R. A., Marcus, D. S., Thompson, P., Saykin, A. J., Correia, S., Schofield, P. R., Rowe, C. C., Fox, N. C., Brickman, A. M., Mayeux, R., McDade, E., Bateman, R., Fagan, A. M., Goate, A. M., Xiong, C., Buckles, V. D., Morris, J. C., & Sperling, R. A.
- Affiliations
- Harvard University (US)
- From the Departments of Neurology (J.P.C., A.P.S., K.J., C.A.S., R.A.S.) and Radiology (K.J.), and Martinos Center for Biomedical Imaging (J.P.C., A.P.S., K.J., C.A.S., R.A.S.), Massachusetts General Hospital, Harvard Medical School, Boston; Department of Radiology, Section of Neuroradiology (T.L.S.B., D.S.M.), Mallinckrodt Institute of Radiology (T.L.S.B., B.M.A., D.S.M.), Departments of Neurology (B.M.A., R.B., A.M.F., V.D.B., J.C.M.), Genetics (A.M.G.), and Psychiatry (A.M.G.), and Division of...
- ORCID
- Chhatwal, Jasmeer P.
- Schultz, Aaron P.
- Johnson, Keith
- Benzinger, Tammie L.S.
- Jack, Clifford
- Ances, Beau M.
- Salloway, Stephen P.
- Ringman, John M.
- Koeppe, Robert A.
- Marcus, Daniel S.
- Thompson, Paul
- Saykin, Andrew J.
- Correia, Stephen
- Schofield, Peter R.
- Fox, Nick C.
- Brickman, Adam M.
- Mayeux, Richard
- McDade, Eric
- Bateman, Randall
- Fagan, Anne M.
- Xiong, Chengjie
- Morris, John C.
- Sperling, Reisa A.
- Venue
- Neurology
- Published
- 2013-08-20
- Volume
- 81
- Issue
- 8
- Pages
- 736-744
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- PMC
- PMC3776464
- OpenAlex
- W2165942026
- Cited by
- 179
- References
- 42
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 8 · 2023: 10 · 2022: 10 · 2021: 14 · 2020: 11 · 2019: 33 · 2018: 18 · 2017: 19 · 2016: 10 · 2015: 12 · 2014: 24 · 2013: 1
- FWCI
- 8.59
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Neurology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- National Institute for Health and Care Research (NF-SI-0508-10123)
- National Institute on Aging (K24AG035007, P50AG005134, U19AG032438, U24AG021886, P30AG062421)
- National Institute of Nursing Research (R01NR012657)
- National Institute of Neurological Disorders and Stroke (P30NS048056)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Keywords
- autosomal dominant Alzheimer's disease, default mode network, functional connectivity, presenilin 1 mutations, amyloid precursor protein mutations, mutation carriers, asymptomatic carriers, precuneus, posterior cingulate cortex, parietal cortex, Clinical Dementia Rating, early biomarkers
- MeSH terms
- Adult, Alzheimer Disease, Brain, Female, Genes, Dominant, Heterozygote, Humans, Male, Nerve Net, Prevalence, Amyloid beta-Protein Precursor, Genetic Predisposition to Disease, Internationality, Presenilin-1, Presenilin-2, Connectome
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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