Visual Impairment and Cognitive Function in Aging Adults: Sex and Age Differences in Mediating Effect of Social Isolation and Depression

center dot PURPOSE: Visual impairment (VI) is prevalent in older adults and associated with cognitive decline. However, the mechanisms through which visual impairment affects cognitive functioning during the aging process are poorly understood. Our study aims to estimate the direct effect of visual acuity on cognitive function and its indirect effect through social isolation and depressive symptoms by sex and age. center dot DESIGN: Cross-sectional study. center dot PARTICIPANTS: 117,231 individuals aged 40-70 participated in the UK Biobank baseline and ocular assessment. Of these, 81% were white, 54% were female, and 45.6% were aged 60-70. The mean age was 56.8 (SD 8.1) years. center dot METHODS: Path analyses with multiple equations were conducted to examine the direct and indirect effects of visual acuity (VA). Stratified analyses by gender and age were performed. center dot MAIN OUTCOME MEASURES: LogMAR VA was the exposure, with social isolation and depressive symptoms as mediators. Cognitive functions, including visual memory, verbal-numerical reasoning, processing speed, and prospective memory, were the outcomes. center dot RESULTS: VA had a direct effect on cognitive function ( B =-0.979 for reasoning and OR = 0.67 for prospective memory). VA also influenced cognition indirectly through social isolation and depressive symptoms. The direct effect of VA on cognitive function was similar in men vs. women and middle-aged vs. older. However, there is a marked difference in the mediating effect via social isolation and depressive symptoms by age and sex. The mediating effect of VI on cognition via social isolation was stronger in older adults than middle-aged and in men than women; while the mediating effect via depressive symptoms was stronger in women and middle-aged individuals. VI had the largest mediating effect via social isolation in older males. center dot CONCLUSION AND RELEVANCE: Vision, social isolation, and depressive symptoms are modifiable factors and can be treated to preserve cognition. Encouraging social engagement among male and older adults with VI and promoting mental health awareness in women and middleaged individuals with VI will reduce the negative impact of VI on cognition, lower dementia risk, and improve the well-being of aging adults. (Am J Ophthalmol 2025;274: 196-208. (c) 2025 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)