The association of retinal vessel calibre, white matter hyperintensities and cognitive decline in community-dwelling older adults

Catherine Robb; Amy Brodtmann; Robyn L. Woods; Ruth E. Trevaks; Stephanie A. Ward; Meng Law; Suzanne G. Orchard; Anne M. Murray; Rory Wolfe; Joanne Ryan; Nigel P. Stocks; Noni Rupasinghe; Raj C. Shah; Christopher M. Reid; Walter P. Abhayaratna; Gary F. Egan; Mohamed Salah Khlif; Trevor T.J. Chong; Liubov Robman; John J. McNeil

doi:10.1093/ageing/afaf243

The association of retinal vessel calibre, white matter hyperintensities and cognitive decline in community-dwelling older adults

Catherine Robb
, Amy Brodtmann
, Robyn L. Woods
, Ruth E. Trevaks
, Stephanie A. Ward
, Meng Law
, Suzanne G. Orchard
, Anne M. Murray
, Rory Wolfe
, Joanne Ryan
, Nigel P. Stocks
, Noni Rupasinghe
, Raj C. Shah
, Christopher M. Reid
, Walter P. Abhayaratna
, Gary F. Egan
, Mohamed Salah Khlif
, Trevor T.J. Chong
, Liubov Robman
, John J. McNeil

Research output: Contribution to journal › Article › peer-review

2 Citations (Scopus)

Abstract

Background Retinal vessel calibres (RVCs) are non-invasive markers of microvascular health and may serve as accessible indicators of cerebral small vessel disease (CSVD) and future cognitive impairment. This study examines whether RVCs are associated with cognitive decline, and how these associations compare with those observed for white matter hyperintensities (WMH), a known marker of CSVD. Methods Data were analysed from community-dwelling participants aged 70+ in the ASPREE trial and sub-studies, free of dementia and cardiovascular disease at baseline. RVCs were measured from fundus photography and WMH volumes from 3 T magnetic resonance imaging. Covariate-adjusted linear mixed-effects models assessed cognitive trajectories relative to baseline RVCs and WMH volumes. Cross-sectional associations between baseline RVCs and WMHs were examined via linear regression. Results This study included 3540 participants with RVC data and 489 with WMH data (median [IQR] age: 73.2 [71.4-76.3] and 72.5 [71.2-75.4] years; female: 52.9% and 47.6%) over a median follow-up of 7.4 [IQR 5.5-8.5] and 3.8 [IQR 2.9-5.3] years, respectively. Baseline RVCs were not significantly associated with cognitive trajectories nor with baseline WMHs. Larger baseline WMH volumes were associated with greater global (Modified Mini-Mental State Examination) decline (mean 0.40 points/year; 95% CI 0.57, 0.22) and declines in delayed memory (HVLT-r) (-0.13 [-0.22, -0.04]), psychomotor function (Symbol Digit Modalities Test) (-0.29 [-0.52, -0.07]) and to a lesser extent, executive function (Controlled Oral Word Association Test) (-0.09 [95% CI -0.22, 0.03]). Conclusion In contrast to WMH volumes, RVCs were not associated with cognitive decline. Exploring longitudinal changes in a broader range of retinal and brain biomarkers may provide deeper insights into the relationship between ocular and cerebral biomarkers in CSVD and clinical outcomes.

Original language	English (US)
Article number	afaf243
Journal	Age and Ageing
Volume	54
Issue number	9
DOIs	https://doi.org/10.1093/ageing/afaf243
Publication status	Published - 1 Sept 2025
Externally published	Yes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

ageing
cognition
microvasculature
older people
retinal vessel calibre
white matter hyperintensities

Access to Document

10.1093/ageing/afaf243

Cite this

Robb, C., Brodtmann, A., Woods, R. L., Trevaks, R. E., Ward, S. A., Law, M., Orchard, S. G., Murray, A. M., Wolfe, R., Ryan, J., Stocks, N. P., Rupasinghe, N., Shah, R. C., Reid, C. M., Abhayaratna, W. P., Egan, G. F., Khlif, M. S., Chong, T. T. J., Robman, L., & McNeil, J. J. (2025). The association of retinal vessel calibre, white matter hyperintensities and cognitive decline in community-dwelling older adults. Age and Ageing, 54(9), Article afaf243. https://doi.org/10.1093/ageing/afaf243

@article{5173270eedca4b01b134cdfe860cc0db,

title = "The association of retinal vessel calibre, white matter hyperintensities and cognitive decline in community-dwelling older adults",

abstract = "Background Retinal vessel calibres (RVCs) are non-invasive markers of microvascular health and may serve as accessible indicators of cerebral small vessel disease (CSVD) and future cognitive impairment. This study examines whether RVCs are associated with cognitive decline, and how these associations compare with those observed for white matter hyperintensities (WMH), a known marker of CSVD. Methods Data were analysed from community-dwelling participants aged 70+ in the ASPREE trial and sub-studies, free of dementia and cardiovascular disease at baseline. RVCs were measured from fundus photography and WMH volumes from 3 T magnetic resonance imaging. Covariate-adjusted linear mixed-effects models assessed cognitive trajectories relative to baseline RVCs and WMH volumes. Cross-sectional associations between baseline RVCs and WMHs were examined via linear regression. Results This study included 3540 participants with RVC data and 489 with WMH data (median [IQR] age: 73.2 [71.4-76.3] and 72.5 [71.2-75.4] years; female: 52.9\% and 47.6\%) over a median follow-up of 7.4 [IQR 5.5-8.5] and 3.8 [IQR 2.9-5.3] years, respectively. Baseline RVCs were not significantly associated with cognitive trajectories nor with baseline WMHs. Larger baseline WMH volumes were associated with greater global (Modified Mini-Mental State Examination) decline (mean 0.40 points/year; 95\% CI 0.57, 0.22) and declines in delayed memory (HVLT-r) (-0.13 [-0.22, -0.04]), psychomotor function (Symbol Digit Modalities Test) (-0.29 [-0.52, -0.07]) and to a lesser extent, executive function (Controlled Oral Word Association Test) (-0.09 [95\% CI -0.22, 0.03]). Conclusion In contrast to WMH volumes, RVCs were not associated with cognitive decline. Exploring longitudinal changes in a broader range of retinal and brain biomarkers may provide deeper insights into the relationship between ocular and cerebral biomarkers in CSVD and clinical outcomes.",

keywords = "ageing, cognition, microvasculature, older people, retinal vessel calibre, white matter hyperintensities",

author = "Catherine Robb and Amy Brodtmann and Woods, \{Robyn L.\} and Trevaks, \{Ruth E.\} and Ward, \{Stephanie A.\} and Meng Law and Orchard, \{Suzanne G.\} and Murray, \{Anne M.\} and Rory Wolfe and Joanne Ryan and Stocks, \{Nigel P.\} and Noni Rupasinghe and Shah, \{Raj C.\} and Reid, \{Christopher M.\} and Abhayaratna, \{Walter P.\} and Egan, \{Gary F.\} and Khlif, \{Mohamed Salah\} and Chong, \{Trevor T.J.\} and Liubov Robman and McNeil, \{John J.\}",

note = "Publisher Copyright: {\textcopyright} 2025 The Author(s). Published by Oxford University Press on behalf of the British Geriatrics Society.",

year = "2025",

month = sep,

day = "1",

doi = "10.1093/ageing/afaf243",

language = "English (US)",

volume = "54",

journal = "Age and Ageing",

issn = "0002-0729",

publisher = "Oxford University Press",

number = "9",

}

Robb, C, Brodtmann, A, Woods, RL, Trevaks, RE, Ward, SA, Law, M, Orchard, SG, Murray, AM, Wolfe, R, Ryan, J, Stocks, NP, Rupasinghe, N, Shah, RC, Reid, CM, Abhayaratna, WP, Egan, GF, Khlif, MS, Chong, TTJ, Robman, L & McNeil, JJ 2025, 'The association of retinal vessel calibre, white matter hyperintensities and cognitive decline in community-dwelling older adults', Age and Ageing, vol. 54, no. 9, afaf243. https://doi.org/10.1093/ageing/afaf243

TY - JOUR

T1 - The association of retinal vessel calibre, white matter hyperintensities and cognitive decline in community-dwelling older adults

AU - Robb, Catherine

AU - Brodtmann, Amy

AU - Woods, Robyn L.

AU - Trevaks, Ruth E.

AU - Ward, Stephanie A.

AU - Law, Meng

AU - Orchard, Suzanne G.

AU - Murray, Anne M.

AU - Wolfe, Rory

AU - Ryan, Joanne

AU - Stocks, Nigel P.

AU - Rupasinghe, Noni

AU - Shah, Raj C.

AU - Reid, Christopher M.

AU - Abhayaratna, Walter P.

AU - Egan, Gary F.

AU - Khlif, Mohamed Salah

AU - Chong, Trevor T.J.

AU - Robman, Liubov

AU - McNeil, John J.

PY - 2025/9/1

Y1 - 2025/9/1

N2 - Background Retinal vessel calibres (RVCs) are non-invasive markers of microvascular health and may serve as accessible indicators of cerebral small vessel disease (CSVD) and future cognitive impairment. This study examines whether RVCs are associated with cognitive decline, and how these associations compare with those observed for white matter hyperintensities (WMH), a known marker of CSVD. Methods Data were analysed from community-dwelling participants aged 70+ in the ASPREE trial and sub-studies, free of dementia and cardiovascular disease at baseline. RVCs were measured from fundus photography and WMH volumes from 3 T magnetic resonance imaging. Covariate-adjusted linear mixed-effects models assessed cognitive trajectories relative to baseline RVCs and WMH volumes. Cross-sectional associations between baseline RVCs and WMHs were examined via linear regression. Results This study included 3540 participants with RVC data and 489 with WMH data (median [IQR] age: 73.2 [71.4-76.3] and 72.5 [71.2-75.4] years; female: 52.9% and 47.6%) over a median follow-up of 7.4 [IQR 5.5-8.5] and 3.8 [IQR 2.9-5.3] years, respectively. Baseline RVCs were not significantly associated with cognitive trajectories nor with baseline WMHs. Larger baseline WMH volumes were associated with greater global (Modified Mini-Mental State Examination) decline (mean 0.40 points/year; 95% CI 0.57, 0.22) and declines in delayed memory (HVLT-r) (-0.13 [-0.22, -0.04]), psychomotor function (Symbol Digit Modalities Test) (-0.29 [-0.52, -0.07]) and to a lesser extent, executive function (Controlled Oral Word Association Test) (-0.09 [95% CI -0.22, 0.03]). Conclusion In contrast to WMH volumes, RVCs were not associated with cognitive decline. Exploring longitudinal changes in a broader range of retinal and brain biomarkers may provide deeper insights into the relationship between ocular and cerebral biomarkers in CSVD and clinical outcomes.

AB - Background Retinal vessel calibres (RVCs) are non-invasive markers of microvascular health and may serve as accessible indicators of cerebral small vessel disease (CSVD) and future cognitive impairment. This study examines whether RVCs are associated with cognitive decline, and how these associations compare with those observed for white matter hyperintensities (WMH), a known marker of CSVD. Methods Data were analysed from community-dwelling participants aged 70+ in the ASPREE trial and sub-studies, free of dementia and cardiovascular disease at baseline. RVCs were measured from fundus photography and WMH volumes from 3 T magnetic resonance imaging. Covariate-adjusted linear mixed-effects models assessed cognitive trajectories relative to baseline RVCs and WMH volumes. Cross-sectional associations between baseline RVCs and WMHs were examined via linear regression. Results This study included 3540 participants with RVC data and 489 with WMH data (median [IQR] age: 73.2 [71.4-76.3] and 72.5 [71.2-75.4] years; female: 52.9% and 47.6%) over a median follow-up of 7.4 [IQR 5.5-8.5] and 3.8 [IQR 2.9-5.3] years, respectively. Baseline RVCs were not significantly associated with cognitive trajectories nor with baseline WMHs. Larger baseline WMH volumes were associated with greater global (Modified Mini-Mental State Examination) decline (mean 0.40 points/year; 95% CI 0.57, 0.22) and declines in delayed memory (HVLT-r) (-0.13 [-0.22, -0.04]), psychomotor function (Symbol Digit Modalities Test) (-0.29 [-0.52, -0.07]) and to a lesser extent, executive function (Controlled Oral Word Association Test) (-0.09 [95% CI -0.22, 0.03]). Conclusion In contrast to WMH volumes, RVCs were not associated with cognitive decline. Exploring longitudinal changes in a broader range of retinal and brain biomarkers may provide deeper insights into the relationship between ocular and cerebral biomarkers in CSVD and clinical outcomes.

KW - ageing

KW - cognition

KW - microvasculature

KW - older people

KW - retinal vessel calibre

KW - white matter hyperintensities

UR - https://www.scopus.com/pages/publications/105016389135

U2 - 10.1093/ageing/afaf243

DO - 10.1093/ageing/afaf243

M3 - Article

C2 - 40966613

AN - SCOPUS:105016389135

SN - 0002-0729

VL - 54

JO - Age and Ageing

JF - Age and Ageing

IS - 9

M1 - afaf243

ER -

The association of retinal vessel calibre, white matter hyperintensities and cognitive decline in community-dwelling older adults

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Keywords

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