Neighborhood deprivation and midlife cognition: Evidence of a modifiable vascular pathway involving health behaviors and cerebral small vessel disease.

1. Department of Psychiatry, School of Clinical Medicine, Cambridge Biomedical Campus, University of Cambridge, Cambridge, UK.
Authors
Low A¹
Prats-Sedano MA¹
McKiernan E¹
Carter SF¹
Stefaniak JD¹
Su L¹
McKeever A¹
Dounavi ME¹
O'Brien JT¹
(9 authors)
2. Department of Psychology, University of Cambridge, Cambridge, UK.
Authors
Tsvetanov KA^{2,

4}
(1 author)
3. Edinburgh Dementia Prevention, University of Edinburgh, Edinburgh, UK.
Authors
Ntailianis G³
Muniz-Terrera G³
Bridgeman K³
Gregory S³
Ritchie K³
Ritchie CW³
(6 authors)
4. Department of Clinical Neurosciences, Cambridge Biomedical Campus, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
Authors
Tsvetanov KA^{2,

4}
Nannoni S⁴
(2 authors)
5. Institute of Neuroscience, Trinity College Dublin, College Green, Lloyd Building, Trinity College, Dublin, Ireland.
Authors
Lawlor B⁵
Naci L⁵
Connolly C⁵
(3 authors)

Show all (7)

Alzheimer's & Dementia : the Journal of the Alzheimer's Association, 01 Nov 2025, 21(11):e70756
https://doi.org/10.1002/alz.70756 PMID: 41190623 PMCID: PMC12587304

This article is in the Europe PMC Open access subset. Refer to the copyright information in the article for licensing details.

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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.

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Funding

Funders who supported this work.

Alzheimer's Association (1)

Grant ID: TriBEKa‐17‐519007
publications

Alzheimer's Society (3)

Grant ID: 178
publications
Grant ID: 264
publications
Grant ID: 329
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Alzheimer's Association (1)

Grant ID: TriBEKa-17-519007
publications

Alzheimer's Research UK (1)

Grant ID: ARUK-SRF2017B-1
publications

Alzheimer's Society (5)

Grant ID: 17
publications
PREVENT Research Programme
Professor Craig Ritchie, Imperial College London
Grant ID: 178
publications
Grant ID: 264
publications
The PREVENT Project
Professor Craig Ritchie, University of Edinburgh
Grant ID: 329
publications
Grant ID: 602
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