Abstract
Objective: The objective of this study was 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. Methods: We included 888 participants aged 59+ years from the Rush Memory and Aging Project (MAP) and 303,887 participants aged 55+ years from the 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 (eg, Alzheimer's disease [AD], Lewy bodies, and 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. Results: In MAP, compared to ≤100 mg/day, caffeine intake >100 mg/day was associated with a significantly higher HR (95% confidence interval [CI]) of all-cause (HR = 1.35, 95% CI = 1.03–1.76) and AD (HR = 1.41, 95% CI = 1.07–1.85) dementia. Caffeine intake was not associated with cognitive decline. In UKB, compared to ≤100 mg/day, the HRs (95% CI) of all-cause dementia for consuming 100 ≤ 200, 200 ≤ 300, 300 ≤ 400, and > 400 mg/day were 0.83 (95% CI = 0.72–0.94), 0.74 (95% CI = 0.64–0.85), 0.74 (95% CI = 0.64–0.85), and 0.92 (95% CI = 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 >100 mg/day was associated with lower neocortical type Lewy bodies (odds ratio (95%CI): 0.40 (95% CI = 0.21–0.75). Interpretation: 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. ANN NEUROL 2022;91:834–846.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 834-846 |
| Number of pages | 13 |
| Journal | Annals of neurology |
| Volume | 91 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jun 2022 |
Funding
This study was supported by the National Institute on Aging (K01AG053477, P30AG013854, R01AG17917, and R01AG054476). Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the authors and do not necessarily reflect the view of the National Institute on Aging. This research has been conducted using the UK Biobank Resource (Application #21394). Computations in this paper were run on the Quest cluster supported in part through the computational resources and staff contributions provided for the Quest high performance computing facility at Northwestern University, which is jointly supported by the Office of the Provost, the Office for Research, and Northwestern University Information Technology. This research has been conducted using the UK Biobank Resource (Application #21394). Computations in this paper were run on the Quest cluster supported in part through the computational resources and staff contributions provided for the Quest high performance computing facility at Northwestern University, which is jointly supported by the Office of the Provost, the Office for Research, and Northwestern University Information Technology. This study was supported by the National Institute on Aging (K01AG053477, P30AG013854, R01AG17917, and R01AG054476). Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the authors and do not necessarily reflect the view of the National Institute on Aging.
ASJC Scopus subject areas
- Neurology
- Clinical Neurology