Presence and progression of white matter hyperintensities and cognition: a meta-analysis.

OBJECTIVE: We aimed to quantify the effects of white matter hyperintensities (WMHs) on specific cognitive functions with particular attention to WMH progression and localization. METHODS: PubMed (January 1990-July 2013) and bibliographies from included articles were used. Studies that were included (1) used MRI; (2) had a population-based or case-control design with a healthy control group that could be used for analysis; (3) matched/adjusted for age, sex, and education; and (4) addressed ≥1 predefined cognitive domains with ≥1 validated neuropsychological tests. Data were independently extracted by 2 investigators. Pearson r was extracted/calculated and used as the common metric for the effect size across studies. RESULTS: Twenty-three cross-sectional and 14 longitudinal studies were included with a total of 8,685 and 7,731 participants. Presence of WMHs was significantly associated with concurrent cognitive deficits in all examined domains: general intelligence (Fisher z -0.10, 95% confidence interval [CI] -0.19 to -0.04), memory (-0.08, -0.13 to -0.06), processing speed (-0.11, -0.17 to -0.07), attention and executive functions (-0.11, -0.16 to -0.07), and perception/construction (-0.15, -0.21 to -0.07). Similar effect sizes were observed for cognitive decline over time. WMH progression was associated with greater cognitive decline, particularly for general intelligence (Fisher z -0.31, 95% CI -0.5 to -0.02) and attention and executive functions (-0.32, -0.34 to -0.28). CONCLUSIONS: The small but robust and consistent effects of WMHs on all cognitive domains suggest a more global effect on cognition than previously thought. Progression of WMHs was associated with even worse cognitive functioning, most pronounced in attention and executive functioning.