Low, A., Tsvetanov, K.A., Ntailianis, G. et al. (19 more authors) (2025) Neighborhood deprivation and midlife cognition: Evidence of a modifiable vascular pathway involving health behaviors and cerebral small vessel disease. Alzheimer's & Dementia, 21 (11). e70756. ISSN: 1552-5260
Abstract
INTRODUCTION
Neighborhood deprivation increases dementia risk, although mechanisms remain unclear. We tested a framework in which modifiable risk factors and cerebral small vessel disease (SVD) mediate the link between neighborhood deprivation and cognition.
METHODS
In 585 cognitively healthy midlife adults (ages 40–59), neighborhood deprivation was derived from postcodes, cognition was assessed using the COGNITO, lifestyle risk factors were measured using clinical assessments, and SVD (white matter hyperintensities, lacunes, microbleeds, perivascular spaces) was assessed on 3T magnetic resonance imaging. Multivariate analyses examined association pathways among these variables.
RESULTS
Neighborhood deprivation was associated with poorer cognition (r = 0.36, p < 0.001), greater prevalence of modifiable risk factors (r = 0.36, p < 0.001), and greater SVD burden (β = 0.18, p = 0.008). Serial mediation showed that the effects of deprivation on cognition were indirect, possibly operating via lifestyle risk and SVD, explaining 20% of the total effect, whereas SVD alone explained 28%.
DISCUSSION
Neighborhood disadvantage relates to poorer cognition, possibly mediated through vascular risk factors and cerebrovascular disease.
Highlights
Neighborhood deprivation linked to poorer cognition in healthy midlife adults
Deprivation linked to small vessel disease (SVD) and modifiable risk factors (chiefly cardiovascular risk)
Association between deprivation and cognition mediated by modifiable risk and SVD
Mediation was exclusive to hypertensive SVD, but not cerebral amyloid angiopathy (CAA)-related SVD
Metadata
| Item Type: | Article |
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| Authors/Creators: |
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| Copyright, Publisher and Additional Information: | © 2025 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association. This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | brain health disparities; cerebral small vessel disease; dementia prevention; midlife cognition; modifiable risk factors; neighborhood deprivation; structural determinants of health; vascular cognitive impairment |
| Dates: |
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| Institution: | The University of Sheffield |
| Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Medicine and Population Health |
| Date Deposited: | 10 Nov 2025 15:36 |
| Last Modified: | 10 Nov 2025 15:36 |
| Status: | Published |
| Publisher: | Wiley |
| Refereed: | Yes |
| Identification Number: | 10.1002/alz.70756 |
| Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:234252 |

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