Background: Epidemiologic studies have provided inconclusive evidence for a protective effect of caffeine consumption on risk of dementia and cognitive decline. Objective: To summarize literature on the association between caffeine and 1) the risk of dementia and/or cognitive decline, and 2) cognitive performance in individuals with mild cognitive impairment (MCI) or dementia, and 3) to examine the effect of study characteristics by categorizing studies based on caffeine source, quantity and other possible confounders. Methods: We performed a systematic review of caffeine effects by assessing overall study outcomes; positive, negative or no effect. Our literature search identified 61 eligible studies performed between 1990 and 2020. Results: For studies analyzing the association between caffeine and the risk of dementia and/or cognitive decline, 16/57 (28%) studies including a total of 40,707/153,070 (27%) subjects reported positive study outcomes, and 30/57 (53%) studies including 71,219/153,070 (47%) subjects showed positive results that were dependent on study characteristics. Caffeine effects were more often positive when consumed in moderate quantities (100-400mg/d), consumed in coffee or green tea, and in women. Furthermore, four studies evaluated the relationship between caffeine consumption and cognitive function in cognitively impaired individuals and the majority (3/4 [75% ]) of studies including 272/289 subjects (94%) reported positive outcomes. Conclusion: This review suggests that caffeine consumption, especially moderate quantities consumed through coffee or green tea and in women, may reduce the risk of dementia and cognitive decline, and may ameliorate cognitive decline in cognitively impaired individuals.