The temporal relationships between white matter hyperintensities, neurodegeneration, amyloid beta, and cognition
Year: 2020
Type: article
Abstract: ABSTRACT INTRODUCTION Cognitive decline in Alzheimer’s disease is associated with amyloid-β accumulation, neurodegeneration and cerebral small vessel disease, but the temporal relationships between these factors is not well established. METHODS Data included white matter hyperintensity (WMH) load, grey matter (GM) atrophy and Alzheimer’s Disease Assessment Scale-Cognitive-Plus (ADAS13) scores for 720 participants and cerebrospinal fluid amyloid (Aβ1-42) for 461 participants from the Alzheimer’s Disease Neuroimaging Initiative. Linear regressions were used to assess the relationships between baseline WMH, GM, and Aβ1-42 to changes in WMH, GM, Aβ1-42, and cognition at one-year follow-up. RESULTS Baseline WMHs and Aβ1-42 predicted WMH increase and GM atrophy. Baseline WMHs, GM, and Aβ1-42 predicted worsening cognition. Only baseline Aβ1-42 predicted change in Aβ1-42. DISCUSSION Baseline WMHs lead to greater future GM atrophy and cognitive decline, suggesting that WM damage precedes neurodegeneration and cognitive decline. Baseline Aβ1-42 predicted WMH increase, suggesting a potential role of amyloid in WM damage. Research in Context Systematic Review : Both amyloid β and neurodegeneration are primary pathologies in Alzheimer’s disease. White matter hyperintensities (indicative of presence of cerebrovascular disease) might also be part of the pathological changes in Alzheimer’s. However, the temporal relationship between white matter hyperintensities, amyloid β, neurodegeneration, and cognitive decline is still unclear. Interpretation : Our results establish a potential temporal order between white matter hyperintensities, amyloid β, neurodegeneration, and cognitive decline, showing that white matter hyperintensities precede neurodegeneration and cognitive decline. The results provide some evidence that amyloid β deposition, in turn, precedes accumulation of white matter hyperintensities. Future Directions : The current findings reinforce the need for future longitudinal investigations of the mechanisms through which white matter hyperintensities impact the aging population in general and Alzheimer’s disease patients, in particular.
DOI: 10.1002/dad2.12091
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,200
Funders: National Science Foundation, U.S. Department of Defense, Foundation for the National Institutes of Health, Alzheimer's Association, 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 of Biomedical Imaging and Bioengineering
Awards: G1012222616, G104586243, G1298807586, G1554142629, G1593117279, G1650819308, G1823308732, G1880935189, Alzheimer's Disease Neuroimaging Initiative, G2100670906, G2105457377, G2152643862, G2189010064, G2340207221, G2423387114, G2471646051, G2522063444, G2835601961, G29951154, G3130427885, G3131374986, G3146424788, G3216574877, G3553156159, G3705772492, G3710456697, G3752451908, G3870774570, G3908963977, G3966393351, G4119534169, G43180419, G4401988282, G4475667458, G4501223628, G4800177743, G4860885537, 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)", G5389965057, G5654639750, G5740349702, G5850682332, G613619302, G6173816828, G6210868510, G6371410416, G6412110892, G6447063303, G6719828067, G6792506723, G6899163935, G6948409098, G72415811, G7298697282, G7414321945, G764699806, G7799614282, G781725486, G8228018387, G8281378126, G8301434335, G839208290, G8852128998, G8895907669, G8897063270, G8957659042, G9000039018, G9000074849, G9000122335, G920654007
OpenAlex ID: W3093190276