Biomarkers.

Background: In recent efforts to improve early identification, staging, and prediction of risk of persons at risk for vascular contributions to cognitive impairment and dementia (VCID) in relation with small vessel disease (SVD), the MarkVCID consortium has worked to identify and validate fluid- and imaging-based biomarkers for SVD associated with VCID. Free water (FW) measured derived from diffusion tensor imaging and one of the selected neuroimaging biomarker "kits", has been demonstrated to have excellent instrumental validity and to be a sensitive biomarker of cognitive performances. We sought to further examine FW clinical relevance by investigating whether FW predicts cognitive worsening over time.

Biomarkers.

Background: The MarkVCID consortium was established to address the paucity of biomarkers for vascular contributions to cognitive impairment and dementia (VCID), a leading cause of dementia. Plasma neurofilament light (NfL), a neuroaxonal injury marker elevated in several neurological and neurodegenerative diseases, was selected as one of the first biomarkers to be examined. We performed comprehensive instrumental and clinical validation of the Quanterix Simoa NfL assay using the first MarkVCID cohort.

Biomarkers.

Background: The location of proposed brain MRI markers of small vessel disease (SVD) might reflect their pathogenesis and may translate into differential associations with cognition. We derived regional MRI markers of SVD and studied: (i) associations with cognitive performance, (ii) patterns most likely to reflect underlying SVD, (iii) mediating effects on the relationships of age and cardiovascular disease (CVD) risk with cognition.

Method: In 891 participants from The Multi-Ethnic Study of Atherosclerosis, we segmented enlarged perivascular spaces (ePVS), white matter hyperintensities (WMH) and microbleeds (MBs) using deep learning-based algorithms, and calculated white matter (WM) microstructural integrity measures of fractional anisotropy (FA), trace (TR) and free water (FW) using automated DTI-processing pipelines.

Biomarkers.

Background: APOE genotype is the most important genetic risk factor for Alzheimer's disease (AD), but whether it affects the proteins associated with AD risk is unclear. Circulating proteins may reveal biology underlying pathologic processes.

Methods: We evaluated log2 standardized levels of 4979 proteins quantified using modified aptamer technology [SomaScan] in plasma from 2725 participants in the Cardiovascular Health Study who were free of dementia and stroke.

Biomarkers.

Background: Peak-width of skeletonized mean diffusivity (PSMD) is an emerging biomarker of cerebral small vessel disease (cSVD)-related vascular contributions to cognitive impairment and dementia (VCID). Higher PSMD values reflect greater white matter microstructural damage, and prior research has related PSMD to sporadic and monogenic forms of cSVD and worse cognitive function. Therefore, we proposed PSMD as a risk stratification biomarker for VCID.