Abstract
Background Previous research suggests that white matter hyperintensities, amyloid, and tau contribute to age-related cognitive decline. It remains unknown as to how these factors relate to one another and how they jointly contribute to cognitive decline in normal aging. This project examines the association between these pathologies and their relationship to cognitive decline.
Methods Cognitively normal older adult data from the Alzheimer’s Disease Neuroimaging Initiative were examined. Participants were included if they had no subjective cognitive decline, had baseline white matter hyperintensity, CSF Aß42/40, CSF pTau181, and cognitive scores. Of the 102 participants included, only 79 had follow-up cognitive scores. Linear regressions examined the influence of white matter hyperintensities, amyloid, and tau on baseline and follow-up cognitive scores. Linear regressions also examined the association of amyloid and tau on white matter hyperintensities and between tau and amyloid.
Results Increased white matter hyperintensity load was associated with lower baseline memory (ß= -0.20, p =.046), follow-up executive functioning (ß= -0.32, p<.001), and follow-up ADAS-13 (ß=2.69, p<.001) scores. White matter hyperintensities were not related to pTau or Aß42/40. Lower Aß42/40 was associated with increased pTau (p=.025). pTau was not associated with decline in any cognitive score. Lower Aß42/40 was associated with lower baseline (p=.015) but not follow-up executive function.
Discussion White matter hyperintensities may be one of the earliest pathologies observed in healthy older adults that contribute to cognitive decline. The inclusion of white matter hyperintensities as an additional marker for early cognitive decline may improve our current understanding of age-related changes.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
↵‡ Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf
Funding information Alzheimer’s Disease Neuroimaging Initiative; This research was supported by a grant from the Canadian Institutes of Health Research and The Louise & André Charron Family.
Financial Disclosures Dr. Morrison is supported by a Canadian Institute of Health Research Postdoctoral Fellowship Funding Reference Number: MFE-176608.
Dr. Dadar is supported by a scholarship from the Canadian Consortium on Neurodegeneration in Aging as well as an Alzheimer Society Research Program (ASRP) postdoctoral award. The Consortium is supported by a grant from the Canadian 24 Institutes of Health Research with funding from several partners including the Alzheimer Society of Canada, Sanofi, and Women’s Brain Health Initiative.
Dr. Villeneuve reports work supported by a Canada Research Chair, a Canadian Institutes of Health Research Foundation Grant, a Canada Fund for Innovation Grant, an Alzheimer’s Association Grant, and an Alzheimer’s society of Canada and Fonds de recherche Sante Quebec fellowship.
Dr. Collins reports receiving research funding from Canadian Institutes of Health research, the Canadian National Science and Engineering Research Council, Brain Canada, the Weston Foundation, and the Famille Louise & André Charron.
