Cannabis use has increased in recent years. However, the long-term implications of cannabis use on brain health remain unknown. We explored the associations of cannabis use with volumetric brain magnetic resonance imaging (MRI) measures in dementia-free older adults. This cross-sectional and longitudinal study included dementia-free participants of the UK Biobank aged ≥60years. Linear regression models were used to evaluate the association of cannabis use and patterns of use with volumetric brain MRI measures. The association between cannabis use and change in brain MRI measures over time was also tested. All models were adjusted for potential confounders. The sample included 19,932 participants (mean age 68 ± 5years, 48% men), 3,800 (19%) reported lifetime use of cannabis. Cannabis use was associated with smaller total, white, grey and peripheral cortical grey matter volumes (B= -6,690 ± 1,157; P< 0.001, B= -4,396 ± 766; P< 0.001, B= -2,140 ± 690; P= 0.002 and B= -2,451 ± 606; P< 0.001, respectively). Among cannabis users, longer duration of use was associated with smaller total brain, grey and cortical grey matter volumes (B= -7,878 ± 2,396; P= 0.001, B= -5,411 ± 1,430; P< 0.001, B = -5,396 ± 1,254; P< 0.001, respectively), and with increased white matter hyperintensity volume (B= 0.09 ± 0.03; P= 0.008). Additionally, current vs. former users (B= -10,432 ± 4,395; P= 0.020) and frequent versus non-frequent users (B= -2,274 ± 1,125; P= 0.043) had smaller grey and cortical grey matter volumes, respectively. No significant associations were observed between cannabis use and change in brain MRI measures. Our findings suggest that cannabis use, particularly longer duration and frequent use, may be related to smaller grey and white matter volumes in older ages, but not to late-life changes in these measures over time.
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