Cerebrovascular health impacts processing speed through anterior white matter alterations: a UK biobank study

Cerebrovascular disease is associated with an increased likelihood of developing dementia. Cerebrovascular risk factors are modifiable and may reduce the risk of later-life cognitive dysfunction, however, the relationship between cerebrovascular risk factors, brain integrity and cognition remains poorly characterised. Using a UK Biobank sample of mid-to-old 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 (e.g. genu, anterior corona radiata), rather than posterior (e.g. splenium, posterior corona radiata)-the mediatory effect of anterior white matter strengthened further with age. Effects were also significantly reduced when considering other forms of cognition, demonstrating both regional- and cognitive-specificity. Our findings also illustrate that cerebrovascular risk factors cross-sectionally predict cognitive processing speed performance, which can be further strengthened by accounting for risk factor duration, particularly hypertensive duration. In summary, our study highlights the vulnerability of anterior regions and sensitivity of processing speed performance to cerebrovascular burden, and show this effect is amplified with age. We also highlight an improved method of cerebrovascular burden quantification, which accounts for factor duration, as well as risk factor presence and degree. Future work will aim to establish the role of medication and effective risk factor control in alleviating or preventing white matter pathology and cognitive dysfunction.