Relationships of visual impairment and eye conditions with imaging markers, cognition, and diagnoses of dementia: a bi-directional Mendelian randomization study

ObjectiveTo evaluate the causal relationships between visual acuity, eye conditions (focusing on cataracts and myopia), and Alzheimer disease (AD) and related dementias. DesignCohort and two sample bi-directional mendelian randomization (MR) study. SettingUK Biobank participants and summary statistics from previously published genome-wide association studies on cataract, myopia, and AD. ParticipantsUK Biobank participants (n=304,953) aged 55-70 without dementia at baseline, underwent genotyping, reported on eye conditions, and a subset completed visual acuity exams (n=113,756) or brain imaging (n=36,855) Main outcome measuresAll-cause dementia, AD, and vascular dementia (VaD) identified from electronic medical records. ResultsThe sample averaged 62.1 years (SD=4.1) of age at baseline, 4.7% had cataracts, and 3.9% had worse than 20/40 vision. History of cataracts (HR=1.18, 95% CI: 1.07 to 1.29) and 20/40 vision (HR=1.35, 95% CI: 1.06 to 1.70) were associated with higher hazard of all-cause dementia. In MR analyses to estimate causal effects, cataracts increased risk of VaD inverse-variance weighted (OR=1.92, 95% CI: 1.26-2.92) borderline increased all-cause dementia (OR =1.21, 95% CI: 0.98 to 1.50) but not AD (OR=1.01, 95% CI: 0.97-1.06). There was no significant association between observed or genetic risk for myopia and dementia. In MR for reverse causality using genetic risk for AD, AD was not significantly associated with cataracts (inverse-variance weighted OR=0.99, 95% CI: 0.96 to 1.01). Genetic risk for cataracts were associated with smaller total brain ({beta}= -597.4 mm3, 95% CI: -1077.9 to -117.0) and grey matter volumes ({beta}= -375.2 mm3, 95% CI: -680.1 to -70.2), but not other brain regions or cognition. ConclusionsOur findings suggest cataracts increase risk of dementia and may reduce brain volume. This lends further support to the hypothesis that cataract extraction may reduce risk for dementia.