Cerebral blood flow in small vessel disease: a systematic review and meta-analysis

White matter hyperintensities (WMHs) are frequent on neuroimaging of older people and are a key feature of cerebral small vessel disease (SVD). They are commonly attributed to chronic hypoperfusion, although whether low cerebral blood flow (CBF) is cause or effect is unclear. We systematically reviewed studies that assessed CBF in SVD patients, performed meta-analysis and sensitivity analysis of potential confounders. 38 studies (n=4006) met the inclusion criteria, including four longitudinal and 34 cross-sectional studies. Most CBF data were from grey matter. 24 cross-sectional studies (n=1161) were meta-analysed, showing that CBF was lower in subjects with more WMH, globally and in most grey and white matter regions (e.g. mean global CBF: standardised mean difference -0.71, 95% CI -1.12, -0.30). These CBF differences were attenuated by excluding studies in dementia or that lacked age-matching. Four longitudinal studies (n=1079) gave differing results, e.g.: more baseline WMH predated falling CBF (3.9y, n=575); CBF was low in regions that developed WMH (1.5y, n=40). CBF is lower in subjects with more WMH cross-sectionally, but evidence for falling CBF predating increasing WMH is conflicting. Future studies should be longitudinal, obtain more white matter data, use better age-correction and stratify by clinical diagnosis.