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: 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.

Biomarkers.

Background: Cerebral small vessel disease (cSVD), as defined by neuroimaging characteristics such as white matter hyperintensities (WMHs), cerebral microhemorrhages (CMHs), and lacunar infarcts, is highly prevalent and has been associated with dementia risk and other clinical sequelae. Although risk factors for cSVD have been identified, little is known about the biological processes and molecular mediators that influence cSVD development and progression.

Methods: Within the Atherosclerosis Risk in Communities (ARIC) study, we used SomaScan Multiplexed Proteomic technology to relate 4,877 plasma proteins to concurrently measured MRI-defined cSVD characteristics, including WMHs, CMHs, and lacunar infarcts, in late-life (n=1508; mean age: 76).

Public Health.

Background: Estimates of the prevalence of preclinical amyloid positivity in the US general population are of great interest to the field, but difficult to measure and thus unavailable in representative studies. A statistical approach from causal inference, 'transport', may allow for improved generalizability of findings from a sample of persons from one population to another. We aimed to explore the feasibility and validity of extending results from a deeply-phenotyped convenience sample, the Alzheimer's Disease Neuroimaging Initiative (ADNI), to a representative target sample, the Atherosclerosis Risk in Communities Study PET Amyloid Imaging Study (ARIC-PET) - with "proof of concept" defined by the performance of the transport estimator in recovering the observed prevalence of amyloid positivity in ARIC-PET.

Public Health.

Background: Weakened white matter (WM) integrity is highly associated with dementia risk. Still, not everyone with WM changes develops dementia, suggesting the important role modifiable lifestyle factors may have in reducing dementia risk. We investigated how social relationships in mid-life may modify the association between WM integrity and incident dementia risk within race and sex subgroups.