Abstract
Dementia is a major public health issue with rising prevalence rates, but many individuals remain undiagnosed. Accurate and timely diagnosis is key for the optimal targeting of interventions. A noninvasive, easily measurable peripheral biomarker would have greatest utility in population-wide diagnostic screening. Epigenetics, including DNA methylation, is implicated in dementia; however, it is unclear whether epigenetic changes can be detected in peripheral tissue. This study aimed to systematically review the evidence for an association between dementia and peripheral DNA methylation. Forty-eight studies that measured DNA methylation in peripheral blood were identified, and 67% reported significant associations with dementia. However, most studies were underpowered and limited by their case-control design. We emphasize the need for future longitudinal studies on large well-characterized populations, measuring epigenetic patterns in asymptomatic individuals. A biomarker detectable in the preclinical stages of the disease would have the greatest utility in future intervention and treatment trials.