To examine the association between caffeine intake and cognitive impairment. Caffeine-neuropathology correlations and interactions with lifestyle and genetic factors impacting caffeine metabolism and response were also tested.
We included 888 participants aged 59+ from the Rush Memory and Aging Project(MAP) and 303,887 participants aged 55+ from UK Biobank(UKB). MAP participants took part in annual cognitive testing. Diagnosis of dementia was based on clinical neurological examination and standardized criteria. A subset provided postmortem tissue for neuropathologic evaluation for common age-related diseases (e.g. AD, Lewy bodies, vascular). For UKB, dementia was determined by linked hospital and death records. Self-reported caffeine intake was estimated using food-frequency questionnaires in both cohorts. Cox proportional hazard ratio(HR), regression and mixed models were used to examine associations of caffeine intake with incident dementia, cognitive decline, and neuropathology.
In MAP, compared to ≤100mg/d, caffeine intake >100mg/d was associated with a significantly higher HR(95%CI) of all-cause[1.35(1.03,1.76)] and Alzheimer's[1.41(1.07,1.85)] dementia. Caffeine intake was not associated with cognitive decline. In UKB, compared to ≤100mg/d, the HRs(95%CI) of all-cause dementia for consuming 100≤200, 200≤300, 300≤400 and >400mg/d were 0.83(0.72,0.94), 0.74(0.64,0.85), 0.74(0.64,0.85) and 0.92(0.79,1.08), respectively. Similar results were observed for Alzheimer's dementia. In MAP, caffeine intake was inversely associated with postmortem Lewy bodies but no other age-related pathologies. Caffeine intake >100mg/d was associated with lower neocortical type Lewy bodies[Odds ratio(95%CI): 0.40(0.21,0.75)].
Caffeine intake was inconsistently associated with clinical dementia; potentially explained by cohort differences in underlying dementia etiology. Lewy bodies may link caffeine to lower risk in some persons.