Etiology of White Matter Hyperintensities in Autosomal Dominant and Sporadic Alzheimer Disease.

Autor:	Shirzadi Z; Massachusetts General Hospital, Brigham and Women's Hospital, Harvard Medical School, Boston., Schultz SA; Massachusetts General Hospital, Brigham and Women's Hospital, Harvard Medical School, Boston., Yau WW; Massachusetts General Hospital, Brigham and Women's Hospital, Harvard Medical School, Boston., Joseph-Mathurin N; Washington University in St Louis School of Medicine, St Louis, Missouri., Fitzpatrick CD; Massachusetts General Hospital, Brigham and Women's Hospital, Harvard Medical School, Boston., Levin R; Massachusetts General Hospital, Brigham and Women's Hospital, Harvard Medical School, Boston., Kantarci K; Department of Radiology, Mayo Clinic, Rochester, Minnesota., Preboske GM; Department of Radiology, Mayo Clinic, Rochester, Minnesota., Jack CR Jr; Department of Radiology, Mayo Clinic, Rochester, Minnesota., Farlow MR; Indiana Alzheimer's Disease Research Center, Indianapolis., Hassenstab J; Washington University in St Louis School of Medicine, St Louis, Missouri., Jucker M; Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.; German Center for Neurodegenerative Diseases (DZNE), Tübingen, Tübingen, Germany., Morris JC; Washington University in St Louis School of Medicine, St Louis, Missouri., Xiong C; Washington University in St Louis School of Medicine, St Louis, Missouri., Karch CM; Washington University in St Louis School of Medicine, St Louis, Missouri., Levey AI; Emory University School of Medicine, Atlanta, Georgia., Gordon BA; Washington University in St Louis School of Medicine, St Louis, Missouri., Schofield PR; Neuroscience Research Australia, Sydney, New South Wales, Australia.; School of Biomedical Sciences, University of New South Wales, Sydney, New South Wales, Australia., Salloway SP; Alpert Medical School of Brown University, Providence, Rhode Island., Perrin RJ; Washington University in St Louis School of Medicine, St Louis, Missouri., McDade E; Washington University in St Louis School of Medicine, St Louis, Missouri., Levin J; Department of Neurology, Ludwig-Maximilians-Universität München, German Center for Neurodegenerative Diseases, site Munich, Munich Cluster for Systems Neurology, Munich, Germany., Cruchaga C; Washington University in St Louis School of Medicine, St Louis, Missouri., Allegri RF; Fleni Neurological Institute, Buenos Aires, Argentina., Fox NC; UK Dementia Research Institute, University College London, London, United Kingdom., Goate A; Washington University in St Louis School of Medicine, St Louis, Missouri., Day GS; Department of Neurology, Mayo Clinic, Jacksonville, Florida., Koeppe R; Department of Radiology, University of Michigan, Ann Arbor., Chui HC; Keck School of Medicine, University of Southern California, Los Angeles., Berman S; Department of Neurology, University of Pittsburgh, Pittsburgh, Pennsylvania., Mori H; Osaka Metropolitan University Medical School, Osaka, Nagaoka Sutoku University, Osaka City, Niigata, Japan., Sanchez-Valle R; Neurological Tissue Bank Hospital Clinic, IDIBAPS, Barcelona, Spain., Lee JH; Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea., Rosa-Neto P; Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada., Ruthirakuhan M; Sunnybrook Research Institute, University of Toronto, Toronto, Ontario, Canada., Wu CY; Sunnybrook Research Institute, University of Toronto, Toronto, Ontario, Canada., Swardfager W; Sunnybrook Research Institute, University of Toronto, Toronto, Ontario, Canada., Benzinger TLS; Washington University in St Louis School of Medicine, St Louis, Missouri., Sohrabi HR; Centre for Healthy Ageing, School of Psychology, Health Future Institute, Murdoch University, Perth, Western Australia, Australia., Martins RN; School of Medical and Health Sciences, Edith Cowan University, Perth, Western Australia, Australia., Bateman RJ; Washington University in St Louis School of Medicine, St Louis, Missouri., Johnson KA; Massachusetts General Hospital, Brigham and Women's Hospital, Harvard Medical School, Boston., Sperling RA; Massachusetts General Hospital, Brigham and Women's Hospital, Harvard Medical School, Boston., Greenberg SM; Massachusetts General Hospital, Brigham and Women's Hospital, Harvard Medical School, Boston., Schultz AP; Massachusetts General Hospital, Brigham and Women's Hospital, Harvard Medical School, Boston., Chhatwal JP; Massachusetts General Hospital, Brigham and Women's Hospital, Harvard Medical School, Boston.
Jazyk:	angličtina
Zdroj:	JAMA neurology [JAMA Neurol] 2023 Dec 01; Vol. 80 (12), pp. 1353-1363.
DOI:	10.1001/jamaneurol.2023.3618
Abstrakt:	Importance: Increased white matter hyperintensity (WMH) volume is a common magnetic resonance imaging (MRI) finding in both autosomal dominant Alzheimer disease (ADAD) and late-onset Alzheimer disease (LOAD), but it remains unclear whether increased WMH along the AD continuum is reflective of AD-intrinsic processes or secondary to elevated systemic vascular risk factors. Objective: To estimate the associations of neurodegeneration and parenchymal and vessel amyloidosis with WMH accumulation and investigate whether systemic vascular risk is associated with WMH beyond these AD-intrinsic processes. Design, Setting, and Participants: This cohort study used data from 3 longitudinal cohort studies conducted in tertiary and community-based medical centers-the Dominantly Inherited Alzheimer Network (DIAN; February 2010 to March 2020), the Alzheimer's Disease Neuroimaging Initiative (ADNI; July 2007 to September 2021), and the Harvard Aging Brain Study (HABS; September 2010 to December 2019). Main Outcome and Measures: The main outcomes were the independent associations of neurodegeneration (decreases in gray matter volume), parenchymal amyloidosis (assessed by amyloid positron emission tomography), and vessel amyloidosis (evidenced by cerebral microbleeds [CMBs]) with cross-sectional and longitudinal WMH. Results: Data from 3960 MRI sessions among 1141 participants were included: 252 pathogenic variant carriers from DIAN (mean [SD] age, 38.4 [11.2] years; 137 [54%] female), 571 older adults from ADNI (mean [SD] age, 72.8 [7.3] years; 274 [48%] female), and 318 older adults from HABS (mean [SD] age, 72.4 [7.6] years; 194 [61%] female). Longitudinal increases in WMH volume were greater in individuals with CMBs compared with those without (DIAN: t = 3.2 [P = .001]; ADNI: t = 2.7 [P = .008]), associated with longitudinal decreases in gray matter volume (DIAN: t = -3.1 [P = .002]; ADNI: t = -5.6 [P < .001]; HABS: t = -2.2 [P = .03]), greater in older individuals (DIAN: t = 6.8 [P < .001]; ADNI: t = 9.1 [P < .001]; HABS: t = 5.4 [P < .001]), and not associated with systemic vascular risk (DIAN: t = 0.7 [P = .40]; ADNI: t = 0.6 [P = .50]; HABS: t = 1.8 [P = .06]) in individuals with ADAD and LOAD after accounting for age, gray matter volume, CMB presence, and amyloid burden. In older adults without CMBs at baseline, greater WMH volume was associated with CMB development during longitudinal follow-up (Cox proportional hazards regression model hazard ratio, 2.63; 95% CI, 1.72-4.03; P < .001). Conclusions and Relevance: The findings suggest that increased WMH volume in AD is associated with neurodegeneration and parenchymal and vessel amyloidosis but not with elevated systemic vascular risk. Additionally, increased WMH volume may represent an early sign of vessel amyloidosis preceding the emergence of CMBs.
Databáze:	MEDLINE
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