Robb Catherine, Brodtmann Amy, Woods Robyn L, Trevaks Ruth E, Ward Stephanie A, Law Meng, Orchard Suzanne G, Murray Anne M, Wolfe Rory, Ryan Joanne, Stocks Nigel P, Rupasinghe Noni, Shah Raj C, Reid Christopher M, Abhayaratna Walter P, Egan Gary F, Khlif Mohamed Salah, Chong Trevor T J, Robman Liubov, McNeil John J
Industrial Transformation Training Centre for Optimal Ageing, Monash University, Melbourne, Victoria, Australia.
School of Psychological Sciences, Monash University, Melbourne, Victoria, Australia.
Age Ageing. 2025 Aug 29;54(9). doi: 10.1093/ageing/afaf243.
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.
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.
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]).
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.
视网膜血管管径（RVC）是微血管健康的无创标志物，可作为脑小血管疾病（CSVD）和未来认知障碍的可及指标。本研究探讨RVC是否与认知衰退相关，以及这些关联与CSVD的已知标志物白质高信号（WMH）相比如何。
对ASPREE试验及子研究中70岁及以上的社区居住参与者的数据进行分析，这些参与者在基线时无痴呆和心血管疾病。通过眼底照片测量RVC，通过3T磁共振成像测量WMH体积。协变量调整的线性混合效应模型评估相对于基线RVC和WMH体积的认知轨迹。通过线性回归研究基线RVC与WMH之间的横断面关联。
本研究纳入了3540名有RVC数据的参与者和489名有WMH数据的参与者（年龄中位数[四分位间距]：73.2[71.4 - 76.3]岁和72.5[71.2 - 75.4]岁；女性：52.9%和47.6%），中位随访时间分别为7.4[四分位间距5.5 - 8.5]年和3.8[四分位间距2.9 - 5.3]年。基线RVC与认知轨迹及基线WMH均无显著关联。更大的基线WMH体积与更大的整体（改良简易精神状态检查）衰退（平均0.40分/年；95%置信区间0.57，0.22）以及延迟记忆（HVLT - r）衰退（-0.13[-0.22，-0.04]）、精神运动功能（符号数字模态测验）衰退（-0.29[-0.52，-0.07]）相关，在较小程度上还与执行功能（受控口语词语联想测验）衰退（-0.09[95%置信区间-0.22，0.03]）相关。
与WMH体积不同，RVC与认知衰退无关。探索更广泛的视网膜和脑生物标志物的纵向变化可能会更深入地洞察CSVD中眼部和脑部生物标志物之间的关系以及临床结局。
