CAFFEINE AND COFFEE INTAKE AND THE RISK OF ALZHEIMER’S DISEASE PROGRESSION: A SYSTEMATIC REVIEW AND META-ANALYSIS: A SYSTEMATIC REVIEW

Background: Alzheimer’s disease (AD) is the most prevalent form of dementia, contributing to significant disability and dependency in older adults worldwide. With more than 55 million people currently affected, identifying modifiable lifestyle factors to delay disease onset or progression has become a global health priority. Caffeine, predominantly consumed as coffee, has been proposed as a neuroprotective compound through adenosine receptor antagonism, antioxidant activity, and anti-inflammatory mechanisms. Understanding its potential role in preserving cognition may inform preventive and therapeutic strategies. Objective: To systematically review and quantify the relationship between caffeine or coffee consumption and the risk of Alzheimer’s disease progression. Methods: This systematic review and meta-analysis followed PRISMA 2020 guidelines and was registered in PROSPERO (ID pending). A comprehensive search of PubMed/MEDLINE, Embase, Web of Science, Scopus, PsycINFO, and the Cochrane Library was performed for studies published from January 2012 to September 2025. Eligible designs included prospective cohort, case–control, and randomized controlled trials that evaluated caffeine or coffee intake and AD progression using validated tools such as the Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR), and Alzheimer’s Disease Assessment Scale–Cognitive Subscale (ADAS-Cog). Two reviewers independently conducted data extraction and quality assessment. Pooled effect estimates were calculated using a random-effects model, with heterogeneity assessed by I² statistics. Publication bias was examined using funnel plots and Egger’s regression test. Results: Fifteen studies including 5,420 participants were analyzed. Higher caffeine intake was associated with a significant reduction in AD progression: MMSE hazard ratio (HR) 0.76 (95% CI 0.68–0.85), CDR HR 0.81 (95% CI 0.72–0.91), and ADAS-Cog HR 0.79 (95% CI 0.71–0.89). Subgroup analysis demonstrated stronger protective effects among high consumers (>300 mg/day; HR 0.71) compared to light consumers (<100 mg/day; HR 0.94). Gender-based differences were modest, with slightly stronger benefits in men. Heterogeneity was moderate (I² = 44–55%), yet sensitivity analyses confirmed the stability of findings. Publication bias was low. Conclusion: Moderate-to-high caffeine and coffee consumption was consistently linked with slower cognitive decline, reduced Alzheimer’s disease progression, and improved memory outcomes. These findings highlight caffeine as a low-cost, accessible dietary factor with potential to complement existing therapeutic approaches to AD management.