Schedule of Events | Symposia

Cannabis use, cognitive functioning, and dementia risk: an observational and Mendelian randomization study

Poster Session E - Monday, March 31, 2025, 2:30 – 4:30 pm EDT, Back Bay Ballroom/Republic Ballroom

Saba Ishrat¹ (saba.ishrat@stx.ox.ac.uk), Klaus Ebmeier¹, Anya Topiwala¹; ¹University of Oxford

Cannabis use for medical and recreational purposes has increased significantly over the past decade. While adverse effects on neurocognitive performance have been reported in adolescents and young adults, its impact on cognition and dementia risk in older adults remains unclear. This study examines the association between lifetime cannabis use, cognitive performance, and dementia risk in older adults. We analysed data from approximately 15,000 to 18,000 lifetime cannabis users and 48,000 to 56,000 controls in UK Biobank, to assess observational associations between cannabis use and cognitive performance. Multiple linear regression and linear mixed-effects models were conducted in R to examine cross-sectional and longitudinal changes, respectively, while adjusting for potential covariates. Additionally, bidirectional two-sample Mendelian randomization analyses were used to investigate potential causal relationships. After false discovery rate correction, lifetime cannabis use was associated with better performance on Numeric Memory (β = 0.110, p < 0.001), and Fluid Intelligence test (β = 0.239, p < 0.001) compared to controls. However, cannabis users experienced greater cognitive decline over time compared to controls in Fluid Intelligence (β = -0.012, p < 0.001) and Trail Making (A) test (β = 0.135, p < 0.001). Genetically-predicted ‘cannabis dependence/abuse’ or ‘lifetime cannabis use’ was not associated with cognitive functioning or with all-cause or vascular dementia. Lifetime cannabis users had better cross-sectional performance but experienced faster decline over time in observational analyses. Genetically-predicted cannabis use did not associate with cognitive or dementia phenotypes, suggesting that higher cross-sectional cognitive performance of cannabis users may be due to residual confounding.

Topic Area: OTHER