Instrumental and biological validation of PSMD as a VCID biomarker.

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.

Synergistic effects of plasma S100b levels and MRI‐based water exchange rate across the blood‐brain‐barrier on memory performance among older adults.

Background: Non‐invasive biofluid and MRI measures of blood‐brain‐barrier (BBB) dysfunction may aid early detection of cerebral small vessel disease (cSVD). Plasma markers of astrocytic function and injury, such as S100 calcium‐binding protein B (S100b), have gained increased attention in relation to BBB integrity and cognition. Here we explored the inter‐relationships between plasma S100b levels, an MRI measure of water exchange rate across the BBB (kw), and cognitive performance among older adults.

Cerebrovascular reactivity (CVR) MRI as a biomarker for cerebral small vessel disease (SVD) related cognitive decline: Multi‐site validation in the MarkVCID Consortium.

Background: Cerebral small vessel disease (SVD) related vascular contributions represent a major factor contributing to cognitive decline and dementia (VCID) in older adults. However, there has not been a validated biomarker for the diagnosis and treatment monitoring of this condition. Recently, the US National Institute on Neurological Disorders and Stroke (NINDS) funded the MarkVCID Consortium to identify and validate clinical‐trial‐ready biomarkers for VCID.

Healthy Dietary Intake Diminishes the Effect of Vascular Pathology on Cognitive Performance in Older Adults.

Background: Cognitive reserve (CR) in the context of Alzheimer’s’ disease has been widely studied, yet less is known about how CR protects against vascular brain pathologies. Here, we explored whether dietary factors might attenuate the association between magnetic resonance imaging (MRI)‐derived vascular biomarkers and cognition.

Method: Seventy‐one older adults (ages 60‐85) were scanned using a 3‐Tesla MRI Siemens Magnetom Prisma at the University of Kentucky.

Cerebrovascular reactivity (CVR) MRI as a biomarker for cerebral small vessel disease (SVD) related cognitive decline: Multi‐site validation in the MarkVCID Consortium.

Background: Cerebral small vessel disease (SVD) related vascular contributions represent a major factor contributing to cognitive decline and dementia (VCID) in older adults. However, there has not been a validated biomarker for the diagnosis and treatment monitoring of this condition. Recently, the US National Institute on Neurological Disorders and Stroke (NINDS) funded the MarkVCID Consortium to identify and validate clinical‐trial‐ready biomarkers for VCID.

A Review of the Association Between Dietary Intake and Brain Iron Levels in Older Adults: Preliminary Findings and Future Directions.

Non-heme iron is essential for critical neuronal functions such as ATP generation, synaptogenesis, neurotransmitter synthesis, and myelin formation. However, as non-heme iron accumulates with age, excessive levels can contribute to oxidative stress, potentially disrupting neuronal integrity and contributing to cognitive decline. Despite growing evidence linking high brain iron with poorer cognitive performance, there are currently no proven methods to reduce brain iron accumulation in aging or to protect cognitive function from iron's negative effects.

Biological validation of peak-width of skeletonized mean diffusivity as a VCID biomarker: The MarkVCID Consortium.

Background: Peak-width of skeletonized mean diffusivity (PSMD), a neuroimaging marker of cerebral small vessel disease (SVD), has shown excellent instrumental properties. Here, we extend our work to perform a biological validation of PSMD.

Methods: We included 396 participants from the Biomarkers for Vascular Contributions to Cognitive Impairment and Dementia (MarkVCID-1) Consortium and three replication samples (Cohorts for Heart and Aging Research in Genomic Epidemiology = 6172, Rush University Medical Center = 287, University of California Davis Alzheimer's Disease Research Center = 567).

Exploring the links among brain iron accumulation, cognitive performance, and dietary intake in older adults: A longitudinal MRI study.

This study evaluated longitudinal brain iron accumulation in older adults, its association with cognition, and the role of specific nutrients in mitigating iron accumulation. MRI-based, quantitative susceptibility mapping estimates of brain iron concentration were acquired from seventy-two healthy older adults (47 women, ages 60-86) at a baseline timepoint (TP1) and a follow-up timepoint (TP2) 2.5-3.

Enlarged perivascular space burden predicts declines in cognitive and functional performance.

Introduction: We evaluated the relationship between baseline enlarged perivascular space (ePVS) burden and later cognitive decline.

Methods: 83 community-dwelling, older adults (aged 56-86) completed three annual cognitive assessments that included the Clinical Dementia Rating (CDR®) Dementia Staging Instrument Sum of Boxes (CDR-SB) and composite measures of executive function and episodic memory. An MRI scan at baseline was used to count ePVS in the basal ganglia and centrum semiovale.

MRI free water mediates the association between water exchange rate across the blood brain barrier and executive function among older adults.

Vascular risk factors contribute to cognitive aging, with one such risk factor being dysfunction of the blood brain barrier (BBB). Studies using non-invasive magnetic resonance imaging (MRI) techniques, such as diffusion prepared arterial spin labeling (DP-ASL), can estimate BBB function by measuring water exchange rate (kw). DP-ASL kw has been associated with cognition, but the directionality and strength of the relationship is still under investigation.

Regional differences in the link between water exchange rate across the blood-brain barrier and cognitive performance in normal aging.

The blood-brain barrier (BBB) undergoes functional changes with aging which may contribute to cognitive decline. A novel, diffusion prepared arterial spin labeling-based MRI technique can measure the rate of water exchange across the BBB (k) and may thus be sensitive to age-related alterations in water exchange at the BBB. However, studies investigating relationships between k and cognition have reported different directions of association.

Association of Baseline Cerebrovascular Reactivity and Longitudinal Development of Enlarged Perivascular Spaces in the Basal Ganglia.

Background: Increasing evidence suggests that enlarged perivascular spaces (ePVS) are associated with cognitive dysfunction in aging. However, the pathogenesis of ePVS remains unknown. Here, we tested the possibility that baseline cerebrovascular dysfunction, as measured by a magnetic resonance imaging measure of cerebrovascular reactivity, contributes to the later development of ePVS.

Plasma TDP-43 levels are associated with neuroimaging measures of brain structure in limbic regions.

Introduction: We evaluated the relationship between plasma levels of transactive response DNA binding protein of 43 kDa (TDP-43) and neuroimaging (magnetic resonance imaging [MRI]) measures of brain structure in aging.

Methods: Plasma samples were collected from 72 non-demented older adults (age range 60-94 years) in the University of Kentucky Alzheimer's Disease Research Center cohort. Multivariate linear regression models were run with plasma TDP-43 level as the predictor variable and brain structure (volumetric or cortical thickness) measurements as the dependent variable.

MRI free water as a biomarker for cognitive performance: Validation in the MarkVCID consortium.

Introduction: To evaluate the clinical validity of free water (FW), a diffusion tensor imaging-based biomarker kit proposed by the MarkVCID consortium, by investigating the association between mean FW (mFW) and executive function.

Methods: Baseline mFW was related to a baseline composite measure of executive function (EFC), adjusting for relevant covariates, in three MarkVCID sub-cohorts, and replicated in five, large, independent legacy cohorts. In addition, we tested whether baseline mFW predicted accelerated EFC score decline (mean follow-up time: 1.

Multi-compartment diffusion magnetic resonance imaging models link tract-related characteristics with working memory performance in healthy older adults.

Multi-compartment diffusion MRI metrics [such as metrics from free water elimination diffusion tensor imaging (FWE-DTI) and neurite orientation dispersion and density imaging (NODDI)] may reflect more specific underlying white-matter tract characteristics than traditional, single-compartment metrics [i.e., metrics from Diffusion Tensor Imaging (DTI)].

Enlarged Perivascular Spaces Are Negatively Associated With Montreal Cognitive Assessment Scores in Older Adults.

Emerging evidence suggests that enlarged perivascular spaces (ePVS) may be a clinically significant neuroimaging marker of global cognitive function related to cerebral small vessel disease (cSVD). We tested this possibility by assessing the relationship between ePVS and both a standardized measure of global cognitive function, the Montreal Cognitive Assessment (MoCA), and an established marker of cSVD, white matter hyperintensity volume (WMH) volume. One hundred and eleven community-dwelling older adults (56-86) underwent neuroimaging and MoCA testing.

Instrumental validation of free water, peak-width of skeletonized mean diffusivity, and white matter hyperintensities: MarkVCID neuroimaging kits.

Introduction: To describe the protocol and findings of the instrumental validation of three imaging-based biomarker kits selected by the MarkVCID consortium: free water (FW) and peak width of skeletonized mean diffusivity (PSMD), both derived from diffusion tensor imaging (DTI), and white matter hyperintensity (WMH) volume derived from fluid attenuation inversion recovery and T1-weighted imaging.

Methods: The instrumental validation of imaging-based biomarker kits included inter-rater reliability among participating sites, test-retest repeatability, and inter-scanner reproducibility across three types of magnetic resonance imaging (MRI) scanners using intra-class correlation coefficients (ICC).

Results: The three biomarkers demonstrated excellent inter-rater reliability (ICC >0.

Ironsmith: An automated pipeline for QSM-based data analyses.

Quantitative susceptibility mapping (QSM) is an MRI-based, computational method for anatomically localizing and measuring concentrations of specific biomarkers in tissue such as iron. Growing research suggests QSM is a viable method for evaluating the impact of iron overload in neurological disorders and on cognitive performance in aging. Several software toolboxes are currently available to reconstruct QSM maps from 3D GRE MR Images.

Multi-vendor and multisite evaluation of cerebrovascular reactivity mapping using hypercapnia challenge.

Cerebrovascular reactivity (CVR), which measures the ability of cerebral blood vessels to dilate or constrict in response to vasoactive stimuli such as CO2 inhalation, is an important index of the brain's vascular health. Quantification of CVR using BOLD MRI with hypercapnia challenge has shown great promises in research and clinical studies. However, in order for it to be used as a potential imaging biomarker in large-scale and multi-site studies, the reliability of CO2-CVR quantification across different MRI acquisition platforms and researchers/raters must be examined.

White Matter Hyperintensity Volume and Location: Associations With WM Microstructure, Brain Iron, and Cerebral Perfusion.

Cerebral white matter hyperintensities (WMHs) represent macrostructural brain damage associated with various etiologies. However, the relative contributions of various etiologies to WMH volume, as assessed via different neuroimaging measures, is not well-understood. Here, we explored associations between three potential early markers of white matter hyperintensity volume.

Healthy dietary intake moderates the effects of age on brain iron concentration and working memory performance.

Age-related brain iron accumulation is linked with oxidative stress, neurodegeneration and cognitive decline. Certain nutrients can reduce brain iron concentration in animal models, however, this association is not well established in humans. Moreover, it remains unknown if nutrition can moderate the effects of age on brain iron concentration and/or cognition.

Cortical iron disrupts functional connectivity networks supporting working memory performance in older adults.

Excessive brain iron negatively affects working memory and related processes but the impact of cortical iron on task-relevant, cortical brain networks is unknown. We hypothesized that high cortical iron concentration may disrupt functional circuitry within cortical networks supporting working memory performance. Fifty-five healthy older adults completed an N-Back working memory paradigm while functional magnetic resonance imaging (fMRI) was performed.

Processing of Real-World, Dynamic Natural Stimuli in Autism is Linked to Corticobasal Function.

Many individuals with autism spectrum disorder (ASD) have been shown to perceive everyday sensory information differently compared to peers without autism. Research examining these sensory differences has primarily utilized nonnatural stimuli or natural stimuli using static photos with few having utilized dynamic, real-world nonverbal stimuli. Therefore, in this study, we used functional magnetic resonance imaging to characterize brain activation of individuals with high-functioning autism when viewing and listening to a video of a real-world scene (a person bouncing a ball) and anticipating the bounce.