Progression of White Matter Hyperintensities in Older Adults: A Systematic Review and Meta-Analysis.

White matter hyperintensities (WMH) are ubiquitous on magnetic resonance images (MRI) in older adults. However, the rate and mechanisms of their proliferation remain unclear, as they are inferred mainly from cross-sectional studies and imperfect single indicators of theoretical constructs. To assess the magnitude of WMH change and its modifiers, we conducted a meta-analysis of 54 longitudinal studies. We found the increase in WMH burden over time (pooled effect size) even in the studies with rigorous participant health screening. WMH proliferation was faster in the samples with higher mean age but independent of sample's sex or ethno-racial composition. Higher prevalence of vascular disease in the sample and lower sample average of diastolic or mean arterial pressure at baseline yielded faster mean WMH progression. Lower baseline cognitive status in samples with healthiest participants was associated with faster WMH increase. Automatic and manual methods produced equivalent results, but manual intervention in automatic methods yielded higher estimates. We found no evidence of publication bias. To better quantify the WMH progression and the influence of moderators in future studies, we recommend increasing the number of assessment occasions, applying uniform protocols and instruments, using multiple indicators of risk factors and cognitive outcomes, adding assessment of metabolic, energetic, and hemodynamic properties of the brain, applying state-of-the-art statistical modeling methods, providing comprehensive sample descriptions, and reporting the results in greater detail.