Abstract Introduction Mild cognitive impairment (MCI), Alzheimer’s disease (AD), and dementia are common forms of neurodegenerative cognitive decline in aging populations. Alertness, attention, and sleep patterns are often impaired in dementia and MCI and can affect ongoing cognition. Given the current lack of treatment options, it is important to identify protective factors. Caffeine is a commonly consumed substance which has been demonstrated in previous observational studies to have a protective effect on the onset of MCI and the progression of MCI to AD. Methods A meta-analysis of longitudinal prospective cohort studies published up to December 2017 was conducted comparing highest vs lowest reported category of caffeine consumption on neurodegenerative outcomes. Three databases were searched including PubMed, EMBASE, and Web of Science. Two investigators independently extracted data and assessed study quality. 13 studies were selected including 94880 participants. The effect size was reported as RRs with ORs and HRs treated as approximations of the RRs. Results A meta-analysis conducted using random effects showed a pooled RR of .84, 95% CI (0.75, 0.93) indicating a moderate protective effect in higher levels of caffeine consumption compared to lower levels. By outcome, AD had a RR of 1.14 with 95% CI (0.69, 1.90); dementia had a RR of 0.81 (0.72, 0.92); cognitive decline had a RR of 0.81 (0.55, 1.18); and MCI had a RR of 0.78 (0.65, 0.93). Conclusion Overall this meta-analysis suggests that compared with the lowest category, the highest caffeine intake category is inversely related to the incidence of age-related cognitive disorders, with this relationship being most apparent for dementia and MCI. Given that caffeine is well accepted and consumed widely in a variety of forms, caffeine in moderate doses, may prove beneficial in sustaining cognitive functioning. Further work will examine the hypothesis that increased alertness and attention with caffeine may sustain cognition through use dependent plasticity or circadian modulation. Support None