Cerebral small vessel disease burden and longitudinal cognitive decline from age 73 to 82: the Lothian Birth Cohort 1936

Hamilton, O. K. L. et al. (2021) Cerebral small vessel disease burden and longitudinal cognitive decline from age 73 to 82: the Lothian Birth Cohort 1936. Translational Psychiatry, 11, 376. (doi: 10.1038/s41398-021-01495-4) (PMID:34226517) (PMCID:PMC8257729)

Abstract

Slowed processing speed is considered a hallmark feature of cognitive decline in cerebral small vessel disease (SVD); however, it is unclear whether SVD’s association with slowed processing might be due to its association with overall declining general cognitive ability. We quantified the total MRI-visible SVD burden of 540 members of the Lothian Birth Cohort 1936 (age: 72.6 ± 0.7 years; 47% female). Using latent growth curve modelling, we tested associations between total SVD burden at mean age 73 and changes in general cognitive ability, processing speed, verbal memory and visuospatial ability, measured at age 73, 76, 79 and 82. Covariates included age, sex, vascular risk and childhood cognitive ability. In the fully adjusted models, greater SVD burden was associated with greater declines in general cognitive ability (standardised β: −0.201; 95% CI: [−0.36, −0.04]; pFDR = 0.022) and processing speed (−0.222; [−0.40, −0.04]; pFDR = 0.022). SVD burden accounted for between 4 and 5% of variance in declines of general cognitive ability and processing speed. After accounting for the covariance between tests of processing speed and general cognitive ability, only SVD’s association with greater decline in general cognitive ability remained significant, prior to FDR correction (−0.222; [−0.39, −0.06]; p = 0.008; pFDR = 0.085). Our findings do not support the notion that SVD has a specific association with declining processing speed, independent of decline in general cognitive ability (which captures the variance shared across domains of cognitive ability). The association between SVD burden and declining general cognitive ability supports the notion of SVD as a diffuse, whole-brain disease and suggests that trials monitoring SVD-related cognitive changes should consider domain-specific changes in the context of overall, general cognitive decline.

• Item Type: Articles
• Additional Information: 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 were 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]. JO was supported by the Economic and Social Research Council [ES/S015604/1]. 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.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Hamilton, Dr Olivia
• Authors: Hamilton, O. K. L., Cox, S. R., Okely, J. A., Conte, F., Ballerini, L., Bastin, M. E., Corley, J., Taylor, A. M., Page, D., Gow, A. J., Muñoz Maniega, S., Redmond, P., Valdés-Hernández, M. d. C., Wardlaw, J. M., and Deary, I. J.
• College/School: College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > MRC/CSO SPHSU
• Journal Name: Translational Psychiatry
• Publisher: Springer
• ISSN: 2158-3188
• ISSN (Online): 2158-3188
• Copyright Holders: Copyright © 2021 The Authors
• First Published: First published in Translational Psychiatry 11: 376
• Publisher Policy: Reproduced under a Creative Commons License