Recent studies have shown that neuroimaging markers of cerebral small vessel disease can also regress over time. We investigated the cognitive consequences of regression of small vessel disease markers. Two hundred and seventy-six participants of the RUNDMC study underwent neuroimaging and cognitive assessments at three time-points over 8.7 years. We semi-automatically assessed white matter hyperintensities volumes and manually rated lacunes and microbleeds. We analysed differences in cognitive decline and accompanying brain atrophy between participants with regression, progression and stable small vessel disease by analysis of variance. Fifty-six participants (20.3%) showed regression of small vessel disease markers: 31 (11.2%) white matter hyperintensities regression, 10 (3.6%) vanishing lacunes and 27 (9.8%) vanishing microbleeds. Participants with regression showed a decline in overall cognition, memory, psychomotor speed and executive function similar to stable small vessel disease. Participants with small vessel disease progression showed more cognitive decline compared with stable small vessel disease (p < 0.001 for cognitive index and memory; p < 0.01 for executive function), although significance disappeared after adjusting for age and sex. Loss of total brain, gray matter and white matter volume did not differ between participants with small vessel disease regression and stable small vessel disease, while participants with small vessel disease progression showed more volume loss of total brain and gray matter compared to those with stable small vessel disease (p < 0.05), although significance disappeared after adjustments. Regression of small vessel disease markers was associated with similar cognitive decline compared to stable small vessel disease and did not accompany brain atrophy, suggesting that small vessel disease regression follows a relatively benign clinical course. Future studies are required to validate these findings and to assess the role of vascular risk factor control on small vessel disease regression and possible recovery of clinical symptoms. Our findings of comparable cognitive decline between participants with regression and stable small vessel disease might suggest that small vessel disease regression has a relative benign cognitive outcome.
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