Analyses of subcortical gray structure volumes in non-demented idiopathic Parkinson's disease (PD) often, but not always, show volume loss of the putamen, caudate nucleus, nucleus accumbens, and hippocampus. There is building evidence that structure morphometry might be more sensitive to disease-related processes than volume.

Sepsis disproportionally affects people over the age of 65, and with an exponentially increasing older population, sepsis poses additional risks for cognitive decline. This review summarizes published literature for (1) authorship qualification; (2) the type of cognitive domains most often assessed; (3) timelines for cognitive assessment; (4) the control group and analysis approach, and (5) sociodemographic reporting. Using key terms, a PubMed database review from January 2000 to January 2021 identified 3050 articles, and 234 qualified as full text reviews with 18 ultimately retained as summaries. More than half (61%) included an author with an expert in cognitive assessment. Seven (39%) relied on cognitive screening tools for assessment with the remaining using a combination of standard neuropsychological measures. Cognitive domains typically assessed were declarative memory, attention and working memory, processing speed, and executive function. Analytically, 35% reported on education, and 17% included baseline (pre-sepsis) data. Eight (44%) included a non-sepsis peer group. No study considered sex or race/diversity in the statistical model, and only five studies reported on race/ethnicity, with Caucasians making up the majority (74%). Of the articles with neuropsychological measures, researchers report acute with cognitive improvement over time for sepsis survivors. The findings suggest avenues for future study designs.

Preoperative cognitive reserve and brain integrity may explain commonly observed intraoperative fluctuations seen on a standard anesthesia depth monitor used ubiquitously in operating rooms throughout the nation. Neurophysiological variability indicates compromised regulation and organization of neural networks. Based on theories of neuronal integrity changes that accompany aging, we assessed the relative contribution of: 1) premorbid cognitive reserve, 2) current brain integrity (gray and white matter markers of neurodegenerative disease), and 3) current cognition (specifically domains of processing speed/working memory, episodic memory, and motor function) on intraoperative neurophysiological variability as measured from a common intraoperative tool, the Bispectral Index Monitor (BIS).

Sexual dimorphisms exist in multiple domains, from learning and memory to neurocognitive disease, and even in the immune system. Male sex has been associated with increased susceptibility to infection, as well as increased risk of adverse outcomes. Sepsis remains a major source of morbidity and mortality globally, and over half of septic patients admitted to intensive care are believed to suffer some degree of sepsis-associated encephalopathy (SAE). In the short term, SAE is associated with an increased risk of in-hospital mortality, and in the long term, has the potential for significant impairment of cognition, memory, and acceleration of neurocognitive disease. Despite increasing information regarding sexual dimorphism in neurologic and immunologic systems, research into these dimorphisms in sepsis-associated encephalopathy remains critically understudied. In this narrative review, we discuss how sex has been associated with brain morphology, chemistry, and disease, sexual dimorphism in immunity, and existing research into the effects of sex on SAE.

Greater brain network integrity may associate with physically active lifestyles. Three resting state networks may provide unique insights into known physical activity-mediated brain health benefits: the default mode network (involved with self-monitoring), the salience network (involved in orienting oneself to salient external and internal stimuli), and the central executive network (responsible for higher level cognitive task). The current study explored relationships between system-wide neural network integrity measured by functional magnetic resonance imaging and objectively-measured physical activity. We hypothesize connectivity patterns as measured by fMRI networks will relate to actigraphy markers such that 1) there will be higher connectivity within the central executive network in more physically active individuals, and 2) there will be higher connectivity within the default mode network and salience network in those with higher levels of physical activity.

Chronic pain is variably associated with brain structure. Phenotyping based on pain severity may address inconsistencies. Sociodemographic groups also differ in the experience of chronic pain severity. Whether differences by chronic pain severity and/or sociodemographic groups are indicated in pain-related areas of the brain is unknown. Relations between 2 measures of chronic pain severity and brain structure via T1-weighted MRI were investigated and sociodemographic group differences explored. The observational study included 142 community-dwelling (68 non-Hispanic Black [NHB] and 74 non-Hispanic White [NHW]) adults with/at risk for knee osteoarthritis. Relationships between chronic pain severity, sociodemographic groups, and a priori selected brain structures (postcentral gyrus, insula, medial orbitofrontal, anterior cingulate, rostral middle frontal gyrus, hippocampus, amygdala, thalamus) were explored. Chronic pain severity associated with cortical thickness. NHB participants reported lower sociodemographic protective factors and greater clinical pain compared to NHWs who reported higher sociodemographic protective factors and lower clinical pain. Greater chronic pain severity was associated with smaller amygdala volumes in the NHB group and larger amygdala volumes in the NHW group. Brain structure by chronic pain stage differed between and within sociodemographic groups. Overall, chronic pain severity and sociodemographic factors are associated with pain-related brain structures. Our findings highlight the importance of further investigating social and environmental contributions in the experience of chronic pain to unravel the complex array of factors contributing to disparities. PERSPECTIVE: The study presents data demonstrating structural brain relationships with clinical pain severity, characteristic pain intensity and chronic pain stage, differ by sociodemographic groups. Findings yield insights into potential sources of previous inconsistent pain-brain relationships and highlights the need for future investigations to address social and environmental factors in chronic pain disparities research.

The human brain is a heterogeneous network of connected functional regions; however, most brain network studies assume that all brain connections can be described in a framework of binary connections. The brain is a complex structure of white matter tracts connected by a wide range of tract sizes, which suggests a broad range of connection strengths. Therefore, the assumption that the connections are binary yields an incomplete picture of the brain. Various thresholding methods have been used to remove spurious connections and reduce the graph density in binary networks. But these thresholds are arbitrary and make problematic the comparison of networks created at different thresholds. The heterogeneity of connection strengths can be represented in graph theory by applying weights to the network edges. Using our recently introduced edge weight parameter, we estimated the topological brain network organization using a complimentary weighted connectivity framework to the traditional framework of a binary network. To examine the reproducibility of brain networks in a controlled condition, we studied the topological network organization of a single healthy individual by acquiring 10 repeated diffusion-weighted magnetic resonance image datasets, over a 1-month period on the same scanner, and analyzing these networks with deterministic tractography. We applied a threshold to both the binary and weighted networks and determined that the extra degree of freedom that comes with the framework of weighting network connectivity provides a robust result as any threshold level. The proposed weighted connectivity framework provides a stable result and is able to demonstrate the small world property of brain networks in situations where the binary framework is inadequate and unable to demonstrate this network property.

The current investigation examined verbal memory in idiopathic non-dementia Parkinson's disease and the significance of the left entorhinal cortex and left entorhinal-retrosplenial region connections (via temporal cingulum) on memory impairment in Parkinson's disease.

For adults age 65 and older, the brain shows acute functional connectivity decreases after total knee arthroplasty with the severity of change predicted by preoperative cognitive function and brain disease burden. The extent of acute structural microstructural brain changes acutely after surgery remains unknown within the literature. For the current study, we report on the severity of acute post-surgery microstructural brain changes as measured by diffusion imaging and free-water analysis. Participants who underwent total knee arthroplasty under general anesthesia and non-surgery peers were part of a federally funded prospective cohort investigation involving participants. Recruitment occurred between 2013 and 2017. Data were collected in outpatient and inpatient settings within a university-affiliated medical center. A total of 232 TKA patients were referred by the study surgeon and contacted for study inclusion. Of these, 78 met inclusion and exclusion criteria and completed assessment. Five participants were excluded due to anesthetic protocol changes (spinal instead of general) with an additional 12 excluded for imaging-related complications. The total included sample size was 61. A total of 127 non-surgery participants were screened with 66 enrolled. One non-surgery participant was excluded for an imaging-related complication. Total knee arthroplasty and general anesthetic protocols were standardized. Participants received preoperative neurocognitive assessment and brain magnetic resonance imaging, with repeat imaging 48 h after surgery or pseudo surgery. Free-water analyses were performed using diffusion weighted images and tract-based spatial statistics with baseline cognitive data used to predict free-water changes. Surgery participants had widespread increases in white matter free-water. Surgery participants with higher cognitive functions as measured by immediate memory and less evidence of brain atrophy and disease (i.e., brain integrity) had greater free-water increase. Non-surgery peers had no free-water change. We interpret the surgery group's free-water change as indicating widespread brain white matter glial response, with greater change indicative of better brain response to the acute surgery/anesthesia experience.

Chronic pain is a stressor that affects whole person functioning. Persistent and prolonged activation of the body's stress systems without adequate recovery can result in measurable physiological and neurobiological dysregulation recognized as allostatic load. We and others have shown chronic pain is associated with measures of allostatic load including clinical biomarker composites, telomere length, and brain structures. Less is known regarding how different measures of allostatic load align. The purpose of the study was to evaluate relationships among two measures of allostatic load: a clinical composite and pain-related brain structures, pain, function, and socioenvironmental measures. Participants were non-Hispanic black and non-Hispanic white community-dwelling adults between 45 and 85 years old with knee pain. Data were from a brain MRI, questionnaires specific to pain, physical and psychosocial function, and a blood draw. Individuals with all measures for the clinical composite were included in the analysis (n = 175). Indicating higher allostatic load, higher levels of the clinical composite were associated with thinner insula cortices with trends for thinner inferior temporal lobes and dorsolateral prefrontal cortices (DLPFC). Higher allostatic load as measured by the clinical composite was associated with greater knee osteoarthritis pathology, pain disability, and lower physical function. Lower allostatic load as indicated by thicker insula cortices was associated with higher income and education, and greater physical functioning. Thicker insula and DLPFC were associated with a lower chronic pain stage. Multiple linear regression models with pain and socioenvironmental measures as the predictors were significant for the clinical composite, insular, and inferior temporal lobes. We replicate our previously reported bilateral temporal lobe group difference pattern and show that individuals with high chronic pain stage and greater socioenvironmental risk have a higher allostatic load as measured by the clinical composite compared to those individuals with high chronic pain stage and greater socioenvironmental buffers. Although brain structure differences are shown in individuals with chronic pain, brain MRIs are not yet clinically applicable. Our findings suggest that a clinical composite measure of allostatic load may help identify individuals with chronic pain who have biological vulnerabilities which increase the risk for poor health outcomes.

The clock drawing test (CDT) is a neuropsychological assessment tool to evaluate a patient's cognitive ability. In this study, we developed a Fair and Interpretable Representation of Clock drawing tests (FaIRClocks) to evaluate and mitigate bias against people with lower education while predicting their cognitive status. We represented clock drawings with a 10-dimensional latent embedding using Relevance Factor Variational Autoencoder (RF-VAE) network pretrained on publicly available clock drawings from the National Health and Aging Trends Study (NHATS) dataset. These embeddings were later fine-tuned for predicting three cognitive scores: the Mini-Mental State Examination (MMSE) total score, attention composite z-score (ATT-C), and memory composite z-score (MEM-C). The classifiers were initially tested to see their relative performance in patients with low education (<= 8 years) versus patients with higher education (> 8 years). Results indicated that the initial unweighted classifiers confounded lower education with cognitive impairment, resulting in a 100% type I error rate for this group. Thereby, the samples were re-weighted using multiple fairness metrics to achieve balanced performance. In summary, we report the FaIRClocks model, which a) can identify attention and memory deficits using clock drawings and b) exhibits identical performance between people with higher and lower education levels.

In this study, we investigate the organization of the structural connectome in cognitively well participants with Parkinson's disease (PD-Well; n = 31) and a subgroup of participants with Parkinson's disease who have amnestic disturbances (PD-MI; n = 9). We explore correlations between connectome topology and vulnerable cognitive domains in Parkinson's disease relative to non-Parkinson's disease peers (control, n = 40). Diffusion-weighted MRI data and deterministic tractography were used to generate connectomes. Connectome topological indices under study included weighted indices of node strength, path length, clustering coefficient, and small-worldness. Relative to controls, node strength was reduced 4.99% for PD-Well (p = 0.041) and 13.2% for PD-MI (p = 0.004). We found bilateral differences in the node strength between PD-MI and controls for inferior parietal, caudal middle frontal, posterior cingulate, precentral, and rostral middle frontal. Correlations between connectome and cognitive domains of interest showed that topological indices of global connectivity negatively associated with working memory and displayed more and larger negative correlations with neuropsychological indices of memory in PD-MI than in PD-Well and controls. These findings suggest that indices of network connectivity are reduced in PD-MI relative to PD-Well and control participants.

This prospective investigation examined: 1) processing speed and working memory relative to other cognitive domains in non-demented medically managed idiopathic Parkinson's disease, and 2) the predictive role of cortical/subcortical gray thickness/volume and white matter fractional anisotropy on processing speed and working memory.

The caudate nucleus plays important roles in cognition and affect. Depending on associated connectivity and function, the caudate can be further divided into dorsal and ventral aspects. Dorsal caudate, highly connected to dorsolateral prefrontal cortex (DLPFC), is implicated in executive function and working memory; ventral caudate, more interconnected with the limbic system, is implicated in affective functions such as pain processing. Clinically, certain brain disorders are known to differentially impact dorsal and ventral caudate. Thus, precise parcellation of caudate has both basic and clinical neuroscience significance. In young adults, past work has combined resting-state fMRI functional connectivity with clustering algorithms to define dorsal and ventral caudate. Whether the same approach is effective in older adults and how to validate the parcellation results have not been considered. We addressed these problems by obtaining resting-state fMRI data from 56 older non-demented adults (age: 69.07 ± 5.92 years and MOCA: 25.71 ± 2.46) along with a battery of cognitive and clinical assessments. Connectivity from each voxel of caudate to the rest of the brain was computed using cross correlation. Applying the K-means clustering algorithm to the connectivity patterns with K = 2 yielded two substructures within caudate, which agree well with previously reported dorsal and ventral divisions of caudate. Furthermore, dorsal-caudate-seeded functional connectivity was shown to be more strongly associated with working memory and fluid reasoning composite scores, whereas ventral-caudate-seeded functional connectivity more strongly associated with pain and fatigue severity. These results demonstrate that dorsal and ventral caudate can be reliably identified by combining resting-state fMRI and clustering algorithms in older adults.

This pilot study explored differences in distribution of white matter hyperintensities (called leukoaraiosis; LA) in older adults (mean age = 67 years) with atrial fibrillation (AF) vs. non-AF peers measured by: (1) depth distribution; (2) anterior-posterior distribution; (3) associations between LA and cortical thickness; and (4) presence of lacunae and stroke.