Cognitive and neuroimaging markers for preclinical vascular cognitive impairment

Abstract

Detection of incipient cognitive impairment and dementia pathophysiology is critical to identify preclinical populations and target potentially disease modifying interventions towards them. There are currently concerted efforts for such detection for Alzheimer's disease (AD). By contrast, the examination of cognitive markers and their relationship to biomarkers for Vascular Cognitive Impairment (VCI) is far less established, despite VCI being highly prevalent and often concomitantly presenting with AD. Critically, vascular risk factors are currently associated with the most viable treatment options via pharmacological and non-pharmacological intervention, hence early identification of vascular factors have important implications for modifying dementia disease trajectories. The aim of this review is to examine the current evidence of cognitive marker correlates to VCI pathology. We begin by examining midlife risk factors that predict VCI. Next, discuss preclinical cognitive hallmarks of VCI informed by insights from neuropsychological assessment, network connectivity and ERP/EEG experimental findings. Finally, we discuss limitations of current cognitive assessments and the need for future cognitive test development to inform diagnostic assessment. As well as, intervention outcome measures for preclinical VCI. In turn, these tests will inform earlier detection of vascular changes and allow implementation of disease intervention approaches.

Keywords: AD, Alzheimer's disease; APOE-ε4, Apolipoprotein E Allele 4; Cardiovascular risk; Cerebrovascular change; Cognitive decline in midlife; DMN, default mode network; DTI, diffusion tensor imaging; ERPs, event related potentials; MCI, mild cognitive impairment; Preclinical dementia; VCI, vascular cognitive impairment; Vascular cognitive impairment; Vascular dementia.

Fig.. 1.

Schematic illustration of brain regions implicated and potential model of disconnectivity emerging between parietal sites and connecting anterior regions. Brain image courtesy of Servier Medical Art https://smart.servier.com/.