| Title: |
Etiology of White Matter Hyperintensities in Autosomal Dominant and Sporadic Alzheimer Disease |
| Authors: |
Shirzadi, Z; Schultz, SA; Yau, WYW; Joseph-Mathurin, N; Fitzpatrick, CD; Levin, R; Kantarci, K; Preboske, GM; Jack, CR; Farlow, MR; Hassenstab, J; Jucker, M; Morris, JC; Xiong, C; Karch, CM; Levey, AI; Gordon, BA; Schofield, PR; Salloway, SP; Perrin, RJ; McDade, E; Levin, J; Cruchaga, C; Allegri, RF; Fox, NC; Goate, A; Day, GS; Koeppe, R; Chui, HC; Berman, S; Mori, H; Sanchez-Valle, R; Lee, JH; Rosa-Neto, P; Ruthirakuhan, M; Wu, CY; Swardfager, W; Benzinger, TLS; Sohrabi, HR; Martins, RN; Bateman, RJ; Johnson, KA; Sperling, RA; Greenberg, SM; Schultz, AP; Chhatwal, JP |
| Source: |
JAMA Neurology , 80 (12) pp. 1353-1363. (2023) |
| Publisher Information: |
American Medical Association |
| Publication Year: |
2023 |
| Collection: |
University College London: UCL Discovery |
| Description: |
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 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: ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
text |
| Language: |
English |
| Relation: |
https://discovery.ucl.ac.uk/id/eprint/10185441/2/Fox_Etiology%20of%20White%20Matter%20Hyperintensities%20in%20Autosomal%20Dominant%20and%20Sporadic%20Alzheimer%20Disease_AAM.pdf; https://discovery.ucl.ac.uk/id/eprint/10185441/ |
| Availability: |
https://discovery.ucl.ac.uk/id/eprint/10185441/2/Fox_Etiology%20of%20White%20Matter%20Hyperintensities%20in%20Autosomal%20Dominant%20and%20Sporadic%20Alzheimer%20Disease_AAM.pdf; https://discovery.ucl.ac.uk/id/eprint/10185441/ |
| Rights: |
open |
| Accession Number: |
edsbas.864D82B3 |
| Database: |
BASE |