Associations between total MRI-visible small vessel disease burden and domain-specific cognitive abilities in a community-dwelling older-age cohort

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Abstract

Cerebral small vessel disease (SVD) is a leading cause of vascular cognitive impairment, however the precise nature of SVD-related cognitive deficits, and their associations with structural brain changes, remain unclear. We combined computational volumes and visually-rated MRI markers of SVD to quantify total SVD burden, using data from the Lothian Birth Cohort 1936 (n=540; age:72.6±0.7 years). We found negative associations between total SVD burden and general cognitive ability (standardised β: −0.363; 95 [−0.49, −0.23]; p(FDR)lt;0.001), processing speed (−0.371 [−0.50, −0.24]; p(FDR)lt;0.001), verbal memory (−0.265; [−0.42, −0.11]; p(FDR)=0.002), and visuospatial ability (−0.170; [−0.32, −0.02]; p(FDR)=0.029). Only the association between SVD burden and processing speed remained after accounting for covariance with general cognitive ability (−0.325; [−0.61, −0.04]; p(FDR)=0.029). This suggests that SVD’s association with poorer processing speed is not driven by, but is independent of its association with poorer general cognitive ability. Tests of processing speed may be particularly sensitive to the cognitive impact of SVD, but all major cognitive domains should be tested to determine the full range of SVD-related cognitive characteristics.Competing Interest StatementThe authors have declared no competing interest.Funding StatementThe authors thank all participants of the LBC1936 who have contributed, and continue to contribute to the ongoing study. We thank the radiographers, nurses and Lothian Birth Cohort 1936 research team members who collected, entered and checked data used in this manuscript. We also thank Julie Staals and Tom Booth for their constructive comments on earlier versions of the manuscript. The LBC1936 is supported by Age UK [MR/M01311/1] (http://www.disconnectedmind.ed.ac.uk) and the Medical Research Council [G1001245/96099]. LBC1936 MRI brain imaging was supported by Medical Research Council (MRC) grants [G0701120], [G1001245], [MR/M013111/1] and [MR/R024065/1]. OKLH is funded by the University of Edinburgh College of Medicine and Veterinary Medicine as part of the Wellcome Trust 4-year PhD in Translational Neuroscience at the University of Edinburgh. SRC, JMW, IJD, SMM and LB were supported by MRC grants [MR/M013111/1] and [MR/R024065/1]. SRC and IJD are additionally supported by a National Institutes of Health (NIH) research grant R01AG054628, and IJD was also supported by the Dementias Platform UK [MR/L015382/1]. MVH was supported by the Row Fogo Charitable Trust [BROD.FID3668413]. JMW is supported by the European Union Horizon 2020, (PHC-03-15, project no 666881), “SVDs@Target”, the Fondation Leducq Transatlantic Network of Excellence for the Study of Perivascular Spaces in Small Vessel Disease (ref no. 16 CVD 05), and the UK Dementia Research Institute which receives its funding from DRI Ltd, funded by the UK Medical Research Council, Alzheimer"s Society and Alzheimer"s Research UK.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:Approval for the LBC1936 was obtained from the Scotland A Research Ethics Committee for Scotland (07/MRE00/58). All participants gave written, informed consent.All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesData supporting this study are available upon reasonable request from the corresponding authors.
Original languageUndefined/Unknown
Pages (from-to)2021.02.02.21250986
JournalNeurobiology of Aging
Volume105
Early online date22 Apr 2021
DOIs
Publication statusPublished - Sep 2021

Keywords

  • Acc/In press
  • LBC1936

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