Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Rush Alzheimer's Disease Center, Chicago, IL, USA.
Ann Neurol. 2022 Jun;91(6):834-846. doi: 10.1002/ana.26349. Epub 2022 Mar 31.
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.
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.
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).
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.
本研究旨在探讨咖啡因摄入与认知障碍之间的关联。还测试了咖啡因与神经病理学的相关性以及与生活方式和影响咖啡因代谢和反应的遗传因素的相互作用。
我们纳入了 Rush 记忆与衰老项目（MAP）中 888 名年龄在 59 岁及以上的参与者和 UK 生物银行（UKB）中 303887 名年龄在 55 岁及以上的参与者。MAP 参与者每年参加认知测试。痴呆的诊断基于临床神经学检查和标准化标准。一小部分人提供了用于评估常见与年龄相关疾病（如阿尔茨海默病[AD]、路易体和血管）的死后组织。对于 UKB，痴呆症是通过相关的医院和死亡记录确定的。在两个队列中，通过食物频率问卷来估计咖啡因的摄入量。Cox 比例风险比（HR）、回归和混合模型用于检查咖啡因摄入与新发痴呆、认知衰退和神经病理学之间的关联。
在 MAP 中，与≤100mg/天相比，咖啡因摄入量>100mg/天与全因（HR 95%置信区间[CI]）和 AD（HR 95%CI）痴呆的 HR（95%CI）显著更高（HR=1.35，95%CI=1.03-1.76）。咖啡因摄入与认知衰退无关。在 UKB 中，与≤100mg/天相比，每天摄入 100mg/天的全因痴呆的 HR（95%CI）为 0.83（95%CI=0.72-0.94），100mg/天至 200mg/天为 0.74（95%CI=0.64-0.85），200mg/天至 300mg/天为 0.74（95%CI=0.64-0.85），每天摄入 300mg/天至 400mg/天为 0.74（95%CI=0.64-0.85），每天摄入 400mg/天至 400mg/天为 0.92（95%CI=0.79-1.08）。对于阿尔茨海默病痴呆症也观察到了类似的结果。在 MAP 中，咖啡因摄入与死后路易体呈负相关，但与其他与年龄相关的病理学无关。每天摄入>100mg 咖啡因与新皮质型路易体的风险降低相关（比值比（95%CI）：0.40（95%CI=0.21-0.75）。
咖啡因摄入与临床痴呆之间的关联不一致；可能是由于队列中潜在的痴呆病因学差异所致。路易体可能将咖啡因与某些人的低风险联系起来。ANN NEUROL 2022；91:834-846。
