Cerebral Small Vessel Disease Severity, Progression May Predict Dementia Risk

Baseline SVD severity and SVD progression play a role in the development of incident all-cause dementia.

The severity of cerebral small vessel disease (SVD) at baseline and SVD progression are independently associated with a higher risk for incident all-cause dementia. This suggests that SVD progression precedes dementia and may be a contributor to its development, thus making SVD a potential modifiable target for delaying dementia. These are the findings of a study published in The American Journal of Psychiatry.

SVD is the main vascular contributor to dementia and cognitive decline. Although a causal association appears to exist between magnetic resonance imaging (MRI) indicators of SVD and dementia, it remains to be confirmed.

For the study, researchers evaluated the link between baseline SVD severity and SVD progression on MRI markers and incident dementia, based on subtype, among individuals with sporadic SVD over a 14-year follow-up period. The researchers enrolled a total of 503 community-dwelling participants with sporadic SVD and without dementia from the prospective Radboud University Nijmegan Diffusion Tensor and Magnetic Resonance Cohort (RUN DMC) study. RUN DMC was designed to explore the risk factors for and clinical outcomes of SVD.

All participants underwent a brain MRI, and were assessed for study inclusion. MRI findings confirmed a diagnosis of SVD, according to the presence of lacunes or WMHs. Follow-up evaluations occurred in 2011, 2015, and 2020.

A delay in disease onset by merely a few years could reduce the devastating burden of dementia substantially.

The Standards for Reporting Vascular Changes on Neuroimaging (STRIVE) were used to appraise all MRI markers of SVD. Dementia, which was diagnosed based on the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) clinical criteria for “major neurocognitive disorder due to a neurodegenerative disease,” was classified as vascular dementia or Alzheimer disease (AD).

All patients involved in the in-person follow-up visits were initially screened with the Mini Mental State Examination (MMSE) and the Instrumental Activities of Daily Living (IADL) scale. Patients screened positive if they met the following 2 criteria:

  • MMSE score of <26 or a decrease of ≥3 points compared with the prior evaluation
  • Exhibiting an impairment on ≥1 item on the IADL scale (ie, a score of <8)

The mean participant age was 65.7±8.8 years. As an endpoint, dementia was available in 99.0% (498 of 503) of the participants, with 5 individuals lost to follow-up.

Overall, 21.7% (108 of 498) of the participants developed dementia after a median follow-up of 13.2 years (range, 8.8-13.8 years), which yielded an incidence rate of 19.4 per 1000 person-years. In 99.0% (107 of 108) of these patients, the subtype of dementia could be determined, with Alzheimer dementia the most common in 35.2% of participants, vascular dementia in 31.5% of patients, and dementia of mixed etiology (ie, Alzheimer dementia/vascular dementia) in 24.1% of individuals.

The participants who developed dementia were older, reported a lower level of education, experienced a higher burden of baseline MRI markers of SVD, and exhibited worse cognitive performance. Based on dementia subtype, individuals who developed vascular dementia exhibited worse baseline cognitive performance and higher baseline SVD burden per MRI than did those who were diagnosed with either Alzheimer dementia or dementia of mixed etiology.

The following features were all independently associated with all-cause dementia and vascular dementia:

  • Higher baseline WMH volume: hazard ratio (HR), 1.31 per 1-standard deviation (SD) increase; 95% CI, 1.02-1.67; P =.04
  • Presence of diffusion-weighted-imaging-positive lesions: HR, 2.03; 95% CI, 1.01-4.04; P =.04
  • Higher peak width of skeletonized mean diffusivity: HR, 1.24 per 1-SD increase; 95% CI, 1.02-1.51; P =.03

Additionally, progression of WMH volume and of hippocampal volume were significant predictors of all-cause dementia (HR, 1.76 per 1-SD increase; 95% CI, 1.18-2.63;
P =.005).

“Agents improving endothelial dysfunction, blood-brain barrier integrity, and anti-inflammatory effects, but also preventive strategies for managing vascular risk factors earlier in life, have been proposed as potentially promising therapeutic targets for SVD and thus dementia,” the researchers wrote. They concluded, “A delay in disease onset by merely a few years could reduce the devastating burden of dementia substantially.”

Disclosure: Some of the study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 

This article originally appeared on Neurology Advisor


Jacob MA, Cai M, van de Donk V, et al. Cerebral small vessel disease progression and the risk of dementia: a 14-year follow-up study. Am J Psychiatry. Published online April 19, 2023. doi:10.1176/appi.ajp.20220380