Cerebrospinal fluid (CSF) neurofilament light (NFL) is a protein biomarker of axonal injury. To study whether NFL is associated with diffusion tensor imaging (DTI) measurements of white matter (WM) microstructure, Vanderbilt Memory & Aging Project participants with normal cognition (n = 77), early mild cognitive impairment (n = 15), and MCI (n = 55) underwent lumbar puncture to obtain CSF and 3T brain MRI. Voxel-wise analyses cross-sectionally related NFL to DTI metrics, adjusting for demographic and vascular risk factors. Increased NFL correlated with multiple DTI metrics (p-values < 0.05). An NFL × diagnosis interaction (excluding early mild cognitive impairment) on WM microstructure (p-values < 0.05) was detected, with associations strongest among MCI. Multiple NFL × CSF biomarker interactions were detected. Associations between NFL and worse WM metrics were strongest among amyloid-β-negative, tau-positive, and suspected nonamyloid pathology participants. Findings suggest increased NFL, a biomarker of axonal injury, is correlated with compromised WM microstructure. Results highlight the role of elevated NFL in predicting WM damage in cognitively impaired older adults who are amyloid-negative, tau-positive, or meet suspected nonamyloid pathology criteria.

White matter hyperintensities (WMHs) are associated with poorer brain health, but their pathophysiological substrates remain elusive. To better understand the mechanistic underpinnings of WMHs among older adults, this study examined in vivo cerebrospinal fluid biomarkers of β-amyloid42 deposition (Aβ42), hyperphosphorylated tau pathology (p-tau), neurodegeneration (total tau), and axonal injury (neurofilament light; NFL) in relation to log-transformed WMHs volume. Participants free of clinical stroke and dementia were drawn from the Vanderbilt Memory & Aging Project (n=148, 72±6 years). Linear regression models adjusted for age, sex, race/ethnicity, education, intracranial volume, modified Framingham Stroke Risk Profile (excluding points assigned for age), cognitive diagnosis, and APOE-ε4 carrier status. Aβ42 (β=−0.001, p=0.007) and NFL (β=0.0003, p=0.01) concentrations related to WMHs, but neither p-tau nor total tau associations with WMHs reached statistical significance (p-values>0.21). In a combined model, NFL accounted for 3.2% of unique variance in WMHs and Aβ42 accounted for an additional 4.3% beyond NFL, providing novel evidence of the co-occurrence of at least two distinct pathways for WMHs among older adults, including amyloid deposition and axonal injury.

To examine the independent contributions of the Vestibular/Ocular Motor Screening (VOMS) to concussion symptom severity in youths while controlling for computerized neurocognitive screening performance, demographics, and medical history. Study Design: Cross-sectional. Setting: Concussion specialty clinic. Participants: A retrospective review of 278 concussed youths clinical charts resulted in a total of 158 participants (16.5 6 2.8 years, 46.8% women, 4.3 6 3.3 days post-injury) when exclusionary criteria (ie, neurological or substance use disorders, age .21, .14 days since injury, and missing/incomplete data) were applied. Independent Variables: Vestibular/Ocular Motor Screening items and computerized neurocognitive test scores. Main Outcome Measures: Standardized postconcussion symptom scale scores. Results: At the univariate level, all VOMS items were positively associated with concussion symptom severity at small to medium effect sizes (r range 0.26-0.42). Women and individuals with a concussion history and/or Attention Deficit Disorder/Attention Deficit Hyperactivity Disorder diagnosis reported higher VOMS item scores (Ps , 0.10). In a multiple hierarchical regression, the contribution of VOMS item scores was significant and explained 9.6% of the variance in concussion symptom severity after adjustment for sex, baseline VOMS symptom ratings, and ImPACT scores [F(6, 141) 5 3.90, P 5 0.001]. Vertical saccades (b 5 2.22, P 5 0.003) and vertical vestibulo-ocular reflex (VOR; b 5 21.46, P 5 0.004) VOMS items significantly contributed to concussion symptom severity in the multivariable model. Conclusions: Findings from this study provide support for the independent contributions of the VOMS items, particularly vertical saccades and vertical VOR, to acute concussion symptom severity in youths. Further work is warranted for a comparison of the VOMS to the full gold standard of concussion testing (ie, clinical interview, physical examination, balance testing, and neurocognitive assessment).

Objective: Over the last 20 years, the internet has become a fundamental means by which many people with neurocognitive disorders manage their activities of daily living (ADL; e.g., shopping) and engage in health behaviors (e.g., appointment scheduling). The aim of this review is to summarize the emerging literature on the neuropsychology of performance-based tasks of internet navigation skills (INS) as measures of everyday functioning. Method: We performed a structured, qualitative review of the extant literature on INS using PRISMA guidelines. Results: Seventeen peer-reviewed studies met inclusion criteria and their results suggest that performance-based tests of INS: 1) discriminate healthy adults from some neuropsychological populations (e.g., HIV, multiple sclerosis, traumatic brain injury); 2) are associated with performance-based tests of everyday functioning capacity, domain-specific declines in manifest everyday functioning, and self-reported internet behavior, but not global manifest functional status; 3) correlate with standard clinical neuropsychological tests, particularly executive functions and episodic memory; 4) may relate to demographic factors, most notably age; and 5) have largely unknown psychometric properties (e.g., reliability). Conclusions: This review provided early support for the construct validity of performancebased tasks of INS as modern measures of everyday functioning in neuropsychological populations. Future work is needed to refine these tasks, establish their psychometrics, and