Cerebrovascular Health Mediates Processing Speed Change Through Anterior White Matter Alterations: A UK Biobank Study

Abstract Cerebrovascular disease is associated with an increased likelihood of developing dementia. While cardiovascular risk factors are modifiable and may reduce the risk of later-life cognitive dysfunction, the relationship between cerebrovascular risk factors, brain integrity and cognition remains poorly characterised. Using a large UK Biobank sample of predominantly middle-aged adults, without neurological disease, our structural equation mediation models showed that poor cerebrovascular health, indicated by the presence of cerebrovascular risk factors, was associated with slowed processing speed. This effect was best explained by anterior white matter microstructure changes, rather than posterior changes. Effects were also significantly reduced when considering other forms of cognition, demonstrating both regional- and cognitive-specificity of our effects. Critically, our findings also demonstrate that including measures of risk factor duration may be particularly important for improving estimations of cerebrovascular burden. In summary, our study demonstrates the specific impact of early cerebrovascular burden on brain structure and cognitive function, highlighting the necessary next steps for improving cerebrovascular burden quantification and improving clinical predictions.