Serum NfL is increased in patients with an RSSI and the occurrence of new CSVD-related MRI lesions, even when clinically silent. This suggests NfL as a blood biomarker for active CSVD.

Gait and balance impairment is highly prevalent in older people. We aimed to assess whether and how single markers of small vessel disease (SVD) or a combination thereof explain gait and balance function in the elderly. We analysed 678 community-dwelling healthy subjects from the Lothian Birth Cohort 1936 at the age of 71–74 years who had undergone comprehensive risk factor assessment, gait and balance assessment as well as brain MRI. We investigated the impact of individual SVD markers (white matter hyperintensity – WMH, microbleeds, lacunes, enlarged perivascular spaces, brain atrophy) as seen on structural brain MRI and of a global SVD score on the patients’ performance. A regression model revealed that age, sex, and hypertension significantly explained gait speed. Among SVD markers white matter hyperintensity (WMH) score or volume were additional significant and independent predictors of gait speed in the regression model. A similar association was seen with the global SVD score. Our study confirms a negative impact of SVD-related morphologic brain changes on gait speed in addition to age, sex and hypertension independent from brain atrophy. The presence of WMH seems to be the major driving force for SVD on gait impairment in healthy elderly subjects.

Iron accumulation in the basal ganglia is more pronounced in the early than later phases of the disease and occurs independent from other morphologic brain changes. Short-term changes in iron concentration are not associated with disease activity or changes in disability.

The concept of cognitive reserve describes differences between individuals in the ability to compensate age-related brain changes or pathology as a result of greater intellectual enrichment. Cerebral small vessel disease (CSVD) is a common age-related vascular disease of the brain associated with slowly accumulating tissue damage and represents a leading cause of functional loss, disability and cognitive decline in the elderly. The promotion of cognitive reserve might be a valuable possibility to moderate the negative impact of accumulating brain changes associated with CSVD on cognitive function and thus limit the functional consequences of CSVD. We here review existing studies investigating this topic in CSVD and provide conceptual considerations why future research is needed. Relevant studies were identified using the electronic databases PubMed and MEDLINE. Six studies including 7893 subjects were found that all focused on a single feature of CSVD only, i.e., white matter hyperintensities (WMH). We also included one study investigating 247 CADASIL patients. In general, they confirm that higher cognitive reserve (i.e., educational attainment) attenuates the negative impact of WMH on cognition. Further studies should attempt to replicate this association for all features of CSVD and to expand the concept to other areas of functional loss like disordered gait. Finally intervention studies will be needed to define when and how we can still increase our cognitive reserve and what kind and magnitude of protective effects this may offer.