Altered Functional Connectivity in Essential Tremor: A Resting-State fMRI Study

Essential tremor (ET) has been associated with a spectrum of clinical features, with both motor and nonmotor elements, including cognitive deficits. We employed resting-state functional magnetic resonance imaging (fMRI) to assess whether brain networks that might be involved in the pathogenesis of nonmotor manifestations associated with ET are altered, and the relationship between abnormal connectivity and ET severity and neuropsychological function.Resting-state fMRI data in 23 ET patients (12 women and 11 men) and 22 healthy controls (HC) (12 women and 10 men) were analyzed using independent component analysis, in combination with a “dual-regression” technique, to identify the group differences of resting-state networks (RSNs) (default mode network [DMN] and executive, frontoparietal, sensorimotor, cerebellar, auditory/language, and visual networks). All participants underwent a neuropsychological and neuroimaging session, where resting-state data were collected.Relative to HC, ET patients showed increased connectivity in RSNs involved in cognitive processes (DMN and frontoparietal networks) and decreased connectivity in the cerebellum and visual networks. Changes in network integrity were associated not only with ET severity (DMN) and ET duration (DMN and left frontoparietal network), but also with cognitive ability. Moreover, in at least 3 networks (DMN and frontoparietal networks), increased connectivity was associated with worse performance on different cognitive domains (attention, executive function, visuospatial ability, verbal memory, visual memory, and language) and depressive symptoms. Further, in the visual network, decreased connectivity was associated with worse performance on visuospatial ability.ET was associated with abnormal brain connectivity in major RSNs that might be involved in both motor and nonmotor symptoms. Our findings underscore the importance of examining RSNs in this population as a biomarker of disease.     

Blood pressure,executive function,and network connectivity in middle-aged adults at risk of dementia in late life

Midlife blood pressure is associated with structural brain changes, cognitive decline, and dementia in late life. However, the relationship between early adulthood blood pressure exposure, brain structure and function, and cognitive performance in midlife is not known. A better understanding of these relationships in the preclinical stage may advance our mechanistic understanding of vascular contributions to late-life cognitive decline and dementia and may provide early therapeutic targets. To identify resting-state functional connectivity of executive control networks (ECNs), a group independent components analysis was performed of functional MRI scans of 600 individuals from the Coronary Artery Risk Development in Young Adults longitudinal cohort study, with cumulative systolic blood pressure (cSBP) measured at nine visits over the preceding 30 y. Dual regression analysis investigated performance-related connectivity of ECNs in 578 individuals (mean age 55.5 ± 3.6 y, 323 female, 243 Black) with data from the Stroop color–word task of executive function. Greater connectivity of a left ECN to the bilateral anterior gyrus rectus, right posterior orbitofrontal cortex, and nucleus accumbens was associated with better executive control performance on the Stroop. Mediation analyses showed that while the relationship between cSBP and Stroop performance was mediated by white matter hyperintensities (WMH), resting-state connectivity of the ECN mediated the relationship between WMH and executive function. Increased connectivity of the left ECN to regions involved in reward processing appears to compensate for the deleterious effects of WMH on executive function in individuals across the burden of cumulative systolic blood pressure exposure in midlife.

Vascular risk factors (VRF) such as hypertension in midlife are associated with cognitive decline in late life (1–4). Notably, deficits in executive function, such as cognitive flexibility or inhibitory control, are early and “prominent” in vascular-related neurocognitive disorders (5). VRF are also associated with structural MRI brain changes such as white matter hyperintensities (WMH) (6), gray matter atrophy (7), and subcortical morphological changes (8), which may not be reversible. However, functional MRI (fMRI) changes may be detectable prior to irreversible structural damage. fMRI studies have shown that VRF are associated with reduced functional connectivity of brain networks and that this reduced network connectivity is associated with cognitive decline (9, 10). Understanding these relationships in midlife individuals and prior to the clinical onset of cognitive decline could provide significant insight into imaging markers that may identify individuals at risk of cognitive impairment and mechanisms for targeted interventions.In this study, we examined the relationship between blood pressure (BP), executive performance, and resting-state fMRI (rsfMRI) connectivity in participants from the brain substudy of the Coronary Artery Disease in Young Adults (CARDIA) longitudinal cohort study. We hypothesized that greater rsfMRI connectivity of executive control networks (ECN) would be related to better performance in an out-of-scanner executive control (Stroop) task. We further hypothesized that while the previously established relationship of systolic BP (SBP) to Stroop performance (11) would be mediated by WMH, the established relationship between WMH and executive function (12, 13) would be mediated by ECN connectivity.     

Effects of regular cannabis use on neurocognition,brain structure,and function: a systematic review of findings in adults

Background: Cannabis is the most used illicit drug worldwide. The long-standing consequences for the central nervous system associated with frequent cannabis use have not been well delineated and should be determined. Objective: To review recent studies on the effects of regular cannabis use regarding its effects on cognition, brain structure, and function in adults. Methods: A systematic literature review was conducted by performing electronic searches in the PubMed, LILACS, and SciELO databases (2010–2016). The initial search identified 898 records. They were evaluated for relevance according to the inclusion and exclusion criteria and 56 studies were included. Results: The neuropsychological studies provide evidence for subtle cognitive deficits at least 7 days after heavy cannabis use. The structural neuroimaging studies show growing evidence of abnormalities in hippocampus volume and gray matter density of cannabis users relative to controls; however, morphological changes in other brain regions are more controversial. The functional neuroimaging studies suggest an altered pattern of brain activity associated with cannabis use. Conclusion: Although there are several limitations for study comparison and substantial heterogeneity in the findings, the present review suggests that regular cannabis use is associated with mild cognitive changes in addition to structural and functional alterations in the brain in adults. The morphological alterations could ultimately affect brain organization and function, but the associated time course for neuronal recovery as well as the real impact on cognitive functioning remain unknown. Also, it is still unclear whether the identified alterations are as a consequence of or precede cannabis use.     

Cognitive function in acromegaly: description and brain volumetric correlates

In acromegaly, we reported on increased rates of affective disorders such as dysthymia and depression, as well as structural brain changes. Objective of this study was to determine if cognitive impairments in patients with acromegaly exist and whether such impairments are associated with structural brain alterations defined by magnetic resonance imaging (MRI). In this cross-sectional study, 55 patients with biochemically confirmed acromegaly were enrolled. MRI data were compared with 87 control subjects. Main outcome measures were performance levels in 13 cognitive tests covering the domains of attention, memory and executive function, with performance below the cut-off level of the 16th percentile rated as impaired. In addition, individual global and hippocampal volume changes were defined for each patient in reference to a normative sample. We found that up to 33.3% of the patients were impaired in the attention, up to 24.1% in the memory, and up to 16.7% in the executive function domain. 67.3% of the patients failed to reach the cut-off level in at least one subtest. MRI demonstrated increased global, left and right hippocampal grey matter and white matter, particularly early in the disease course. Rather few positive than expected negative correlations could be established between the hippocampal grey matter gain and cognitive performance. Cognitive dysfunction, particularly attentional deficits, are common in acromegaly, rendering neuropsychological testing essential in the diagnostic work-up.     

Pulmonary Function and Cognitive Decline in an Older Chinese Population in Singapore

Abstract

Introduction: Various cognitive deficits associated with reduced pulmonary function are reported in different studies, but the pattern of cognitive deficits across multiple domains and its associated everyday functional disability remain unclear. Methods: We analyzed neuropsychological functioning, cognitive impairment and accompanying disability in instrumental activities of daily living (IADL) associated with reduced pulmonary function in community-living middle-aged and older adults in Singapore. Performance on a comprehensive battery of neuropsychological tests, spirometry and cognitively demanding IADLs were assessed in the population-based Singapore Longitudinal Ageing Studies. Results: Consecutive 10% increase in forced expiratory volume in 1 s (FEV1) as percent of predicted was positively associated with 0.18 points increase in Mini-mental state examination (MMSE) and 0.04 points increase in executive function, independent of age, education and other variables. Subjects with moderate-to-severe airway obstruction showed significantly poorer MMSE score (p for linear trend = 0.001), and information processing speed (p for linear trend < 0.001). FEV1 (per 10% of predicted) was significantly associated with lower risk of cognitive impairment (OR = 0.92, 95% CI: 0.87-0.98, P = 0.005) and cognitive IADL disability (OR = 0.86,95% CI:0.79–0.93, P < 0.001). Pulmonary restriction was associated with greater risk of cognitive impairment (OR = 1.98, 95% CI: 1.26-3.11, P = 0.003) and cognitive IADL disability (OR = 2.43, 95% CI: 1.31-4.53, P = 0.005). Moderate-to-severe airway obstruction (OR = 2.04, 95% CI: 1.11–3.74, P = 0.022) was positively associated with cognitive IADL disability. Conclusion: The findings suggest a measurable but modest cognitive effect of low pulmonary function that was accompanied by corresponding disability in living activities. The effect on executive functioning should be further investigated in longitudinal studies.     

Depression and cognitive functioning in alcoholism

Aims Studies on cognitive processes in alcoholism have reported changes with respect to executive functions and memory, which have been interpreted within the context of different neuropsychological models. The aims of the present study were to investigate (1) the validity of these models and (2) the influence of depression on cognitive functioning in alcoholism. Design, setting and participants In the present investigation, patients suffering from alcoholism (Alc; n = 30), patients with depression but without alcoholism (Dep; n = 28) and healthy controls (HC; n = 28) were compared on a neuropsychological test battery. Measurements The test battery included measurements of mood, memory and executive functions. The possible cumulative effect of alcohol and depression was analysed by comparison of depressed alcoholic patients (Dalc) and non‐depressed alcoholic patients (NDAlc). Findings Group comparisons revealed impairments of alcoholic patients with respect to response inhibition, reasoning and free recall, irrespective of depression. Priming, short‐term memory as well as verbal fluency abilities were unaffected. Depressive patients showed verbal fluency as well as free recall deficits. However, there was no difference in performance between depressed and non‐depressed alcoholics. Conclusions The specific pattern of neuropsychological deficits of the alcoholic patients supports the frontal lobe hypothesis. The results of the present investigation suggest that these deficits are not generally exacerbated by comorbid depressive symptoms. Further studies, however, are desirable to investigate the relation between executive deficits and depression in alcoholics with evidence of major depression.     

The structural brain correlates of cognitive deficits in adults with Klinefelter's syndrome

CONTEXT: Adults with Klinefelter's syndrome (KS) are known to present disturbances of language skills and delayed learning abilities. OBJECTIVES: The aim of this study was to assess brain morphometry in KS and to correlate eventual volumetric changes with performance on neuropsychological tests. PATIENTS: Patients included 18 KS adults and 20 age-matched controls. METHODS: All participants underwent prospectively double-spin-echo brain magnetic resonance imaging and neuropsychological testing of verbal and nonverbal domains. On the axial stack of magnetic resonance imaging slices, regional brain volumes were measured either by automated segmentation (full brain, total cerebrospinal fluid, and ventricular volume) or manual drawing with help of a neuroanatomy atlas (frontal, temporal, and parietal lobes, gray matter component of the lobes, cerebellar hemispheres, and hippocampal complexes). RESULTS: KS patients performed significantly lower than controls on language-related tasks exploring verbal processing speed and verbal executive function. They were diagnosed with significant enlargement of ventricular volume and bilateral reduction of cerebellar hemispheres. Furthermore, after separation of participants according to handedness and after correction of regional brain volumes for atrophy, a significant reduction of left temporal lobe volume was found in KS compared with controls. Ventricular volume was inversely correlated with cognitive function, whereas left temporal lobe volume was positively correlated with language-related tasks. CONCLUSION: This study hypothesizes that supernumerary X-chromosome and/or congenital hypogonadism provoke structural alterations in the subcortical pathways involved in language processing, thus providing a neurobiological substrate for cognitive deficits in KS.     

Relationship between dual‐task performance and neurocognitive measures in older adults with mild cognitive impairment

Aim: The aim of this study was to examine the relationship between dual‐task performance and neurocognitive measures in community‐dwelling older people with mild cognitive impairment (MCI). Methods: A total of 98 subjects (mean age 74.8 years, 52.0% female) participated in the study. We compared 36 participants with amnestic MCI (aMCI) with 62 participants with non‐amnestic MCI (non‐aMCI) on dual‐task performance as measured by reaction time responses. The relationships between dual‐task performance and multiple domains of neurocognitive functions, including general cognitive function, visual memory, working memory, executive function and processing speed, were examined. Results: Although there were no statistically significant group differences in simple reaction times (P = 0.734), the aMCI group showed significantly slower dual‐task reaction times than the non‐aMCI group (P = 0.012). Using multiple regression analysis, we found that there was a significant relationship between executive function and dual‐task reaction times (β = 0.298, P = 0.006). Conclusion: These results showed that aMCI subjects showed a specific deficit in dual‐task performance compared with non‐aMCI subjects, and poor dual‐task performance was associated with declines in executive function in older people with MCI. Future longitudinal and interventional studies should investigate the use of dual‐task testing with varying levels of cognitive demand in older adults at risk of dementia. Geriatr Gerontol Int 2013; 13: 314–321 .     

Cognitive performance in type 1 diabetes patients is associated with cerebral white matter volume

Aims/hypothesis Cognitive performance in type 1 diabetes may be compromised as a result of chronic hyperglycaemia. The aim of this study was to investigate the cognitive functioning of patients with type 1 diabetes (including a subgroup with a microvascular complication) and nondiabetic controls, and to assess the relationship between cognition and cerebral grey and white matter volumes. Materials and methods Twenty-five patients with type 1 diabetes (of whom ten had proliferative retinopathy) and nine nondiabetic controls (matched in terms of sex, age and education) underwent a neuropsychological examination and magnetic resonance imaging of the brain. Fractional brain tissue volumes (tissue volume relative to total intracranial volume) were obtained from each participant. Results Compared with nondiabetic controls, patients with diabetes performed worse on tests measuring speed of information processing and visuoconstruction; patients with microvascular disease performed worse on the former cognitive domain (p = 0.03), whereas patients without complications performed worse on the latter domain (p = 0.01). Patients with a microvascular complication had a significantly smaller white matter volume than nondiabetic controls (p = 0.04), and smaller white matter volume was associated with worse performance on the domains of speed of information processing and attention and executive function. Conclusions/interpretation Patients with diabetes demonstrated several subtle neuropsychological deficits, which were found to be related to white matter volume. Since patients with diabetic retinopathy had a smaller white matter volume, this suggests that cognitive decline is at least partly mediated by microvascular disease. This needs to be addressed in future studies.     

Salience network integrity predicts default mode network function after traumatic brain injury

Efficient behavior involves the coordinated activity of large-scale brain networks, but the way in which these networks interact is uncertain. One theory is that the salience network (SN)--which includes the anterior cingulate cortex, presupplementary motor area, and anterior insulae--regulates dynamic changes in other networks. If this is the case, then damage to the structural connectivity of the SN should disrupt the regulation of associated networks. To investigate this hypothesis, we studied a group of 57 patients with cognitive impairments following traumatic brain injury (TBI) and 25 control subjects using the stop-signal task. The pattern of brain activity associated with stop-signal task performance was studied by using functional MRI, and the structural integrity of network connections was quantified by using diffusion tensor imaging. Efficient inhibitory control was associated with rapid deactivation within parts of the default mode network (DMN), including the precuneus and posterior cingulate cortex. TBI patients showed a failure of DMN deactivation, which was associated with an impairment of inhibitory control. TBI frequently results in traumatic axonal injury, which can disconnect brain networks by damaging white matter tracts. The abnormality of DMN function was specifically predicted by the amount of white matter damage in the SN tract connecting the right anterior insulae to the presupplementary motor area and dorsal anterior cingulate cortex. The results provide evidence that structural integrity of the SN is necessary for the efficient regulation of activity in the DMN, and that a failure of this regulation leads to inefficient cognitive control.     

Cardiopulmonary Fitness Is Associated with Cognitive Performance in Patients with Coronary Artery Disease

OBJECTIVES: To investigate the association between cardiopulmonary fitness and cognitive performance in subjects with coronary artery disease (CAD). DESIGN: Cross‐sectional observational study. SETTING: Outpatient cardiac rehabilitation. PARTICIPANTS: Eighty‐one subjects with CAD. MEASUREMENTS: Cardiopulmonary fitness was assessed by measuring peak oxygen uptake (VO_2Peak) in a standardized exercise stress test. The fraction of the predicted age and sex norm for VO_2Peak was computed for each patient. A battery of neuropsychological tests including the Stroop, Trail‐Making Test Part B, Digit Symbol Coding, Revised Brief Visuospatial Memory Test, California Verbal Learning Test 2nd Edition, and Mini Mental State Examination (MMSE) was administered, from which composite Z‐scores were computed for tasks involving executive function and memory. RESULTS: Executive function, memory, and MMSE scores were correlated with VO_2Peak, but only performance in the executive domain was independently associated with VO_2Peak in multiple linear regression. In a multiple linear regression model controlling for potential clinical confounders, VO_2Peak (β=.666, P<.001) and covariates accounted for 36% of the variance in executive function scores. CONCLUSION: Poorer VO_2Peak is associated with poorer cognition, particularly executive function, in subjects with CAD independent of other cardiac risk factors. Cardiopulmonary fitness may be a protective factor for cognition in patients with CAD.     

Characteristics of neuropsychological functions in inpatients with poorly‐controlled type 2 diabetes mellitus

Aims/Introduction: It has been suggested that type 2 diabetes is associated with cognitive impairment. We investigated the neuropsychological profile of inpatients with poorly controlled type 2 diabetes and assessed the effects of clinical factors on neuropsychological functions. Materials and Methods: Forty‐two patients with type 2 diabetes and 32 non diabetic control subjects were matched for age, sex ratio, and level of education. Attention & working memory, processing speed, verbal memory, visuospatial memory, visuoconstruction, and executive function were tested. Information about physical function, alcohol use, hypertension, dyslipidemia, and myocardial infarction was retrieved from personal interviews and medical records. Results: Diabetic patients demonstrated mild cognitive deterioration in attention & working memory, processing speed, verbal memory, and executive function. In particular, neuropsychological decline became prominent when tasks related with speed and verbal stimuli became unstructured and complex. Age was significantly associated with the majority of neuropsychological tests, whereas tasks dealing with working memory and executive function were associated with age only in the diabetic group. Duration of diabetes was associated with Backward Digit Span. Conclusions: Accelerated aging had a major influence on cognitive decline in the diabetic group, whereas diminished performance in working memory and executive function might have been more related to diabetes‐related cognitive impairment. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2011.00170.x, 2011)     

Dynamic reconfiguration of frontal brain networks during executive cognition in humans

The brain is an inherently dynamic system, and executive cognition requires dynamically reconfiguring, highly evolving networks of brain regions that interact in complex and transient communication patterns. However, a precise characterization of these reconfiguration processes during cognitive function in humans remains elusive. Here, we use a series of techniques developed in the field of “dynamic network neuroscience” to investigate the dynamics of functional brain networks in 344 healthy subjects during a working-memory challenge (the “n-back” task). In contrast to a control condition, in which dynamic changes in cortical networks were spread evenly across systems, the effortful working-memory condition was characterized by a reconfiguration of frontoparietal and frontotemporal networks. This reconfiguration, which characterizes “network flexibility,” employs transient and heterogeneous connectivity between frontal systems, which we refer to as “integration.” Frontal integration predicted neuropsychological measures requiring working memory and executive cognition, suggesting that dynamic network reconfiguration between frontal systems supports those functions. Our results characterize dynamic reconfiguration of large-scale distributed neural circuits during executive cognition in humans and have implications for understanding impaired cognitive function in disorders affecting connectivity, such as schizophrenia or dementia.The era of human brain mapping has demonstrated the power of associating brain regions to specific cognitive functions. However, emerging evidence indicates that many so-called “domain-general” areas engage in multiple functions, differing from “domain-specific” areas such as primary visual cortex that perform a very specific function (1, 2). Such broad engagement is enabled by two fundamental features of brain function: time and interconnectivity. Brain areas and associated circuits or networks may be engaged in tasks differently over time: some transiently and some consistently (2, 3). A fundamental understanding of cognition in general and executive cognition in particular should therefore address the dynamic, interconnected nature of brain function.Here, we use and extend emerging tools from “dynamic network neuroscience,” a field of neuroscientific inquiry that embraces the inherently evolving, interconnected nature of neurophysiological phenomena underlying human cognition (3, 4). Building on the formalism of network science (5), this approach treats the patterns of communication between brain regions as evolving networks and links this evolution to behavioral outcomes. Conceptually, this approach is particularly useful in examining the consistent or transient engagement of neural (or cognitive) circuits or putative functional modules (Fig. 1). We define a network module to be a set of brain regions that are strongly connected to each other and weakly connected to the rest of the network. Using dynamic network-based clustering techniques (6), we seek to observe the flexible recruitment and integration of neural circuits underlying executive function in the form of working memory.Open in a separate windowFig. 1.Network reconfiguration during executive function. (A) We use a numerical n-back task consisting of 0-back and 2-back conditions. (B) We define 270 cortical and subcortical regions of interest (36), and (C) extract the mean time course from each region. (D) A sliding window comprising 15 volumes with no gap was applied to regional mean time courses, and for each window we estimated the functional connectivity between pairs of regions using coherence. This procedure resulted in a sequence of 114 time-ordered adjacency matrices. (E) Using a dynamic community detection algorithm (part 1 in panel), we identified network modules in each time window and tracked their evolution over time. (F) By estimating the probability that a brain region changes its allegiance to modules between any two consecutive time windows (part 2 in panel), we observed that whole-brain flexibility oscillated between unitask (2-back or 0-back only) and dual-task (2-back and 0-back in same time window) conditions.Working memory lies at the interface of perception and action (7) and requires the integration of large-scale neural circuits (8–11). Theoretical frameworks for working memory call on the interplay of distinct components (12) and their integration in broader cognitive circuits (1). The empirical neuroimaging literature has bolstered these conceptualizations by identifying several distinct sets of brain areas underlying working-memory performance (13–17). Nevertheless, a fundamental understanding of the flexible integration and recruitment of these circuits remains incomplete.In the present study, we characterize the time-dependent interactions between putative neural circuits [network modules (3)] underlying working-memory performance in humans as elicited by an n-back task performed during the acquisition of functional MRI (fMRI) data (Fig. 1 A and B). By deploying a sliding time window analysis (18, 19), we capture brain network dynamics during working-memory function (2-back), during a baseline condition (0-back), and in transitions between baseline and task (Fig. 1 C and D). We identify putative functional modules in each time window and track how brain regions change their engagement in these modules over time (Fig. 1 E and F). We quantify those changes over time by flexibility, which measures how often a particular brain region changes its modular allegiance. Based on the cognitive load of the 2-back condition (20–22), we hypothesize that the brain transiently reorganizes functional modules during task performance in comparison with baseline. Furthermore, we hypothesize that this reconfiguration is driven by higher order cognitive control systems, particularly in frontal cortex (2), which are known to play a role in task switching. Finally, based on prior evidence linking network reconfiguration to behavioral adaptation (3), we hypothesize that individuals who display more flexible network structures will perform better than individuals with more rigid network structures.     

Effects of alcoholism severity and smoking on executive neurocognitive function

Aims Neurocognitive deficits in chronic alcoholic men are well documented. Impairments include memory, visual–spatial processing, problem solving and executive function. The cause of impairment could include direct effects of alcohol toxicity, pre‐existing cognitive deficits that predispose towards substance abuse, comorbid psychiatric disorders and abuse of substances other than alcohol. Cigarette smoking occurs at higher rates in alcoholism and has been linked to poor cognitive performance, yet the effects of smoking on cognitive function in alcoholism are often ignored. We examined whether chronic alcoholism and chronic smoking have effects on executive function. Methods Alcoholism and smoking were examined in a community‐recruited sample of alcoholic and non‐alcoholic men (n = 240) using standard neuropsychological and reaction‐time measures of executive function. Alcoholism was measured as the average level of alcoholism diagnoses across the study duration (12 years). Smoking was measured in pack‐years. Results Both alcoholism and smoking were correlated negatively with a composite executive function score. For component measures, alcoholism was correlated negatively with a broad range of measures, whereas smoking was correlated negatively with measures that emphasize response speed. In regression analyses, both smoking and alcoholism were significant predictors of executive function composite. However, when IQ is included in the regression analyses, alcoholism severity is no longer significant. Conclusions Both smoking and alcoholism were related to executive function. However, the effect of alcoholism was not independent of IQ, suggesting a generalized effect, perhaps affecting a wide range of cognitive abilities of which executive function is a component. On the other hand, the effect of smoking on measures relying on response speed were independent of IQ, suggesting a more specific processing speed deficit associated with chronic smoking.     

Neuroimaging and Cognitive Evidence for Combined HIV-Alcohol Effects on the Central Nervous System: A Review

Alcohol use disorder (AUD) among people living with HIV (PLWH) is a significant public health concern. Despite the advent of effective antiretroviral therapy, up to 50% of PLWH still experience worsened neurocognition, which comorbid AUD exacerbates. We report converging lines of neuroimaging and neuropsychological evidence linking comorbid HIV/AUD to dysfunction in brain regions linked to executive function, learning and memory, processing speed, and motor control, and consequently to impairment in daily life. The brain shrinkage, functional network alterations, and brain metabolite disruption seen in individuals with HIV/AUD have been attributed to several interacting pathways: viral proteins and EtOH are directly neurotoxic and exacerbate each other’s neurotoxic effects; EtOH reduces antiretroviral adherence and increases viral replication; AUD and HIV both increase gut microbial translocation, promoting systemic inflammation and HIV transport into the brain by immune cells; and HIV may compound alcohol’s damaging effects on the liver, further increasing inflammation. We additionally review the neurocognitive effects of aging, Hepatitis C coinfection, obesity, and cardiovascular disease, tobacco use, and nutritional deficiencies, all of which have been shown to compound cognitive changes in HIV, AUD, and in their comorbidity. Finally, we examine emerging questions in HIV/AUD research, including genetic and cognitive protective factors, the role of binge drinking in HIV/AUD-linked cognitive decline, and whether neurocognitive and brain functions normalize after drinking cessation.     

Aging-related kidney damage is associated with a decrease in klotho expression and an increase in superoxide production

The purpose of this study was to determine changes in klotho, endothelin (ET) receptors, and superoxide production in kidneys of aged rats and whether these changes are exacerbated in aged rats with cognitive impairment. Twenty aged rats (male, 27 months) were divided into an Old Impaired group (n = 9) and an Old Intact group (n = 11) according to a cognitive function test. A group of 12-month-old rats (n = 10) was used as a Young Intact group. Serum creatinine was increased significantly in the Old Impaired group, suggesting impaired renal function. Aged rats showed glomerulosclerosis and tubulointerstitialfibrosis. These pathological changes were markedly aggravated in the old cognitively impaired than in the old cognitively intact animals. Notably, aged rats demonstrated a significant decrease in klotho protein expression in renal cortex and medulla. Protein expression of IL-6, Nox2, ETa receptors and superoxide production were increased whereas mitochondrial SOD (MnSOD) and ETb receptors expression were decreased in kidneys of the aged rats. Interestingly, these changes were more pronounced in the old impaired than in the old intact rats. In conclusion, the aging-related kidney damage was exacerbated in aged rats with cognitive impairment. Klotho, ETB, and MnSOD were downregulated but ETa, IL-6, Nox2, and superoxide production were upregulated in the aging-related kidney damage. These changes were more pronounced in rats with cognitive impairment.     

Longitudinal relationships between cognitive domains and depression and anxiety symptoms in systemic lupus erythematosus

ObjectivesTo examine i) the relationship between neuropsychological performance and depression and anxiety over time, and ii) the overlap between classification of cognitive dysfunction, anxiety, and depression in SLE.Methods301 patients with SLE were included. Cognition was measured using a modified version of the ACR neuropsychological battery; cognitive dysfunction was defined as z-scores ≤-1.5 on ≥2 domains. Depression and anxiety were measured using the Beck Depression Inventory-II and the Beck Anxiety Inventory, respectively. All measures were assessed at baseline, 6, and 12 months. Their relationships were analyzed using Multiple Factor Analysis (MFA).ResultsAnxiety and depression and neuropsychological performance were stable across time. Factor analysis identified two dimensions explaining 42.2% of the variance in neuropsychological performance. The first dimension (33.1% of the variance) included primarily complex cognitive tests measuring executive function; verbal, visual, and working memory; and complex processing speed. The second dimension (9.1% of the variance) included primarily measures of simple information processing speed or motor dexterity. Anxiety and depression scores were consistently related to the first cognitive dimension. There was substantial overlap in participants classified with cognitive dysfunction and anxiety and depression.ConclusionsDepression and anxiety symptoms in SLE patients are related to a cognitive dimension incorporating memory, executive function and complex processing speed in a stable manner across one year. Many patients with cognitive dysfunction exhibit clinically significant anxiety and depression. Further research should examine whether cognition improves when anxiety and depression are treated and mechanistic links between anxiety and depression and cognitive dysfunction in SLE.     

Physical activity,obesity, and cognitive impairment among women with systemic lupus erythematosus

Objective

To examine relationships of obesity and physical inactivity to cognitive impairment in women with systemic lupus erythematosus (SLE).

Methods

Body composition was measured with dual x‐ray absorptiometry (DXA) for 138 women with SLE. Obesity was defined by total percent body fat. Physical activity was ascertained with the self‐reported International Physical Activity Questionnaire; inactivity was defined as expenditure of <600 metabolic equivalent minutes/week. Cognitive function was assessed with a 12‐index neuropsychological battery. Impairment was defined as age‐adjusted Z scores ≤1.5 SDs below the mean on 1 of 3 of tests completed. Scores were obtained for the total battery and for memory and executive function components. Multivariate analyses examined the relationship of obesity and physical activity, individually and combined, to cognitive impairment, controlling for education, race/ethnicity, disease activity, glucocorticoid use, and depression.

Results

Fifteen percent of subjects were cognitively impaired, 28% were physically inactive, and 50% were obese. Five percent of active women were impaired on the executive function battery compared to 23% of those who were inactive (P = 0.003). Obese women were more likely to be impaired on the total battery (6% versus 23%; P = 0.007) and on the executive function portion (2% versus 19%) than nonobese women. In multivariate analysis, both inactivity and DXA‐defined obesity were significantly associated with impairment in executive function (inactivity: odds ratio [OR] 9.4, 95% confidence interval [95% CI] 1.7–52.8; obesity: OR 14.8, 95% CI 1.4–151.0).

Conclusion

Both obesity and inactivity were significantly and independently associated with impairment in cognitive function. If longitudinal studies show that physical inactivity and obesity are precursors to cognitive impairment, these may become important targets for intervention.