Cataracts are associated with smaller gray matter brain volume among participants in the UK Biobank

Abstract

AbstractBackgroundVisual impairments, including reduced visual acuity and cataracts, are emerging as novel and modifiable risk factors for Alzheimer disease (AD) and related dementias (ADRD). However, it is unclear whether vision impairments or cataracts are associated with structural integrity of brain regions linked to ADRD or other brain regions. We investigate associations between visual acuity, cataracts, genetic risk for cataract, and brain volumes.MethodWe analyzed 33,923 UK Biobank participants aged 55‐82 without dementia at enrollment who underwent brain MRI. Subsets had usable genetic data (n = 29,963) and visual acuity exams (n = 7,837). Participants self‐reported history of cataracts. The following imaging volumes were generated from FreeSurfer segmentations: hippocampal volume, total brain volume, and total gray matter volume. We additionally included an AD signature region defined as the cortical thickness averaged across six relevant brain regions. We calculated a genetic risk score (GRS) for cataract using 43 previously‐reported genetic variants. Linear regressions estimated the associations between brain volumes and visual acuity or self‐reported cataract, separately with adjustment for demographic and clinical confounders, intracranial volume, and imaging center. Linear regressions for brain volume using cataract GRS adjusted for ancestry principal components, sex, age, intracranial volume, and imaging center.ResultThe sample was an average of 66.0 years (SD = 6.26) at imaging, with a cataract prevalence of 2.5% (n = 863). History of cataract was associated with significantly smaller total gray matter volume (β = ‐2483 mm3, 95% CI: ‐4225 to ‐741). Increased genetic risk for cataract was significantly associated with smaller total gray matter (β = ‐485 mm3, 95% CI: ‐732 to ‐138) and total brain volume (β = ‐707 mm3, 95% CI: ‐1192 to ‐221). Neither cataract nor cataract GRS was associated with hippocampal volume or the AD signature region. Poor visual acuity (worse than 20/40 vision) was not significantly associated with any brain volumes.ConclusionHistory of and genetic risk for cataract is associated with smaller total gray matter volume, but not hippocampal volume. Our results suggest that cataract may increase risk of neurodegeneration independent of typical AD, but more investigation is needed.