RT Journal Article
SR Electronic
T1 The Temporal Relationships between White Matter Hyperintensities, Neurodegeneration, Amyloid β, and Cognition
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.05.27.119586
DO 10.1101/2020.05.27.119586
A1 Mahsa Dadar
A1 Richard Camicioli
A1 Simon Duchesne
A1 D. Louis Collins
A1 for the Alzheimer’s Disease Neuroimaging Initiative
YR 2020
UL http://biorxiv.org/content/early/2020/05/30/2020.05.27.119586.abstract
AB 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 ContextSystematic 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.Competing Interest StatementThe authors have declared no competing interest.