Background: Cerebral Small Vessel Disease (SVD); lacunes, Cerebral Microbleeds (CMBs),
and White Matter Hyperintensities (WMH) have a vital role in cognitive impairment and dementia.
SVD in lobar location is related to cerebral amyloid angiopathy, whereas SVD in a deep location with
hypertensive arteriopathy. It remains unclear how different locations of SVD affect long-term cognitive
decline. The present study aimed to analyse the association between different locations and severity
of SVD with global and domain-specific cognitive decline over the follow-up interval of 3 years.
Methods: We studied 428 participants who had performed MRI scans at baseline and at least 3 neuropsychological
assessments. Locations of lacunes and CMBs were categorized into strictly lobar,
strictly deep and mixed-location, WMH volume into anterior and posterior. The National Institute of
Neurological Disorders and Stroke-Canadian Stroke Network Harmonization Neuropsychological
Battery was used to assess cognitive function. To analyse the association between baseline location and
severity of SVD with cognitive decline, linear regression models with generalized estimated equations
were constructed to calculate the mean difference, 95% confidence interval and two-way interaction
factor between time and SVD.
Results: Increased numbers of baseline CMBs were associated with a decline in global cognition as
well as a decline in executive function and memory domains. Location-specific analysis showed similar
results with strictly lobar CMBs. There was no association with strictly deep and mixed-location
CMBs with cognitive decline. Baseline WMH volume was associated with a decline in global cognition,
executive function and memory. Similar results were obtained with anterior and posterior WMH
volumes. Lacunes and their locations were not associated with cognitive decline.
Conclusion: Strictly lobar CMBs, as well as WMH volume in anterior and posterior regions, were
associated with cognitive decline. Future research focuses are warranted to evaluate interventions that
may prevent cognitive decline related to SVD.