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.
View Article and Find Full Text PDFThis 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.
View Article and Find Full Text PDFIntroduction: 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.
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.
View Article and Find Full Text PDFThe 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.
View Article and Find Full Text PDFBackground: 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.
View Article and Find Full Text PDFBackground And Purpose: Cerebral small vessel disease (SVD) has been suggested to contribute to the pathogenesis of Alzheimer's disease (AD). Yet, the role of SVD in potentially contributing to AD pathology is unclear. The main objective of this study was to test the hypothesis that WMHs influence amyloid β (Aβ) levels within connected default mode network (DMN) tracts and cortical regions in cognitively unimpaired older adults.
View Article and Find Full Text PDFIntroduction: 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.
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)].
View Article and Find Full Text PDFEmerging 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.
View Article and Find Full Text PDFIntroduction: 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.
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.
View Article and Find Full Text PDFCerebral 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.
View Article and Find Full Text PDFAge-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.
View Article and Find Full Text PDFExcessive 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.
View Article and Find Full Text PDFAnimate and inanimate objects differ in their intermediate visual features. For instance, animate objects tend to be more curvilinear compared to inanimate objects (e.g.
View Article and Find Full Text PDFThe fusiform and occipital face areas (FFA and OFA) are functionally defined brain regions in human ventral occipitotemporal cortex associated with face perception. There is an ongoing debate, however, whether these regions are face-specific or whether they also facilitate the perception of nonface object categories. Here, we present evidence that, under certain conditions, bilateral FFA and OFA respond to a nonface category equivalently to faces.
View Article and Find Full Text PDFVisuospatial attention often improves task performance by increasing signal gain at attended locations and decreasing noise at unattended locations. Attention is also believed to be the mechanism that allows information to enter awareness. In this experiment, we assessed whether orienting endogenous visuospatial attention with cues differentially affects visual discrimination sensitivity (an objective task performance) and visual awareness (the subjective feeling of perceiving) during the same discrimination task.
View Article and Find Full Text PDFHuman face recognition is often attributed to configural processing; namely, processing the spatial relationships among the features of a face. If configural processing depends on fine-grained spatial information, do visuospatial mechanisms within the dorsal visual pathway contribute to this process? We explored this question in human adults using functional magnetic resonance imaging and transcranial magnetic stimulation (TMS) in a same-different face detection task. Within localized, spatial-processing regions of the posterior parietal cortex, configural face differences led to significantly stronger activation compared to featural face differences, and the magnitude of this activation correlated with behavioral performance.
View Article and Find Full Text PDFMulti-echo fMRI, particularly the multi-echo independent component analysis (ME-ICA) algorithm, has previously proven useful for increasing the sensitivity and reducing false positives for functional MRI (fMRI) based resting state connectivity studies. Less is known about its efficacy for task-based fMRI, especially at the single subject level. This work, which focuses exclusively on individual subject results, compares ME-ICA to single-echo fMRI and a voxel-wise T2(⁎) weighted combination of multi-echo data for task-based fMRI under the following scenarios: cardiac-gated block designs, constant repetition time (TR) block designs, and constant TR rapid event-related designs.
View Article and Find Full Text PDFEveryday objects are often composed of multiple parts, each with a unique surface texture. The neural substrates mediating the integration of surface features on different object parts are not fully understood, and potential contributions by both the ventral and dorsal visual pathways are possible. To explore these substrates, we collected fMRI data while human participants performed a difference detection task on two objects with textured parts.
View Article and Find Full Text PDFAlthough object perception involves encoding a wide variety of object properties (e.g., size, color, viewpoint), some properties are irrelevant for identifying the object.
View Article and Find Full Text PDFGrowing evidence suggests that the functional specialization of the two cortical visual pathways may not be as distinct as originally proposed. Here, we explore possible contributions of the dorsal "where/how" visual stream to shape perception and, conversely, contributions of the ventral "what" visual stream to location perception in human adults. Participants performed a shape detection task and a location detection task while undergoing fMRI.
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