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ObjectivesLatinos are about twice as likely to develop cognitive impairment. Culturally, filial support and familismo are expected within Latino families. Yet approximately twenty percent of Latinos live alone in the United States. The purpose of this study is to explore the concerns and priorities of older Latinos living alone with cognitive impairment, using a precarity framework.MethodWe conducted 22 in-home interviews with older Latinos living alone with cognitive impairment, and we supplemented the interviews with interviews with members of the older adults' social circle and providers. Themes influencing the precarity of Latino older adults living alone were organized through the major areas of the precarity lens; 1) Limited awareness of cognitive impairment; 2) Self-management of cognitive impairment; and 3) Lacking tailored services for cognitive impairment.ResultsLatino culture permeated and intersected across the lived experiences of participants living alone with cognitive impairment. Precarity was prevalent in all participants' lives and was exacerbated by familismo combined with cognitive impairment.ConclusionFindings showed precarity in the experiences the participants shared. Participant narratives reveal how the Latino culture intersects with the experience of precarity while living alone with cognitive impairment, especially in reference to the role that family plays through the expectation of familismo. However, given the difficult demands of employment and raising their own families, familismo can become more like a goal than a practice. Further research is needed to better understand how to bridge the gap between the needs of these older Latino adults living alone with cognitive impairment, their families, and formal services.

BACKGROUND: About one-third of older adults aged 65 years and older often have mild cognitive impairment or dementia. Acoustic and psycho-linguistic features derived from conversation may be of great diagnostic value because speech involves verbal memory and cognitive and neuromuscular processes. The relative decline in these processes, however, may not be linear and remains understudied. OBJECTIVE: This study aims to establish associations between cognitive abilities and various attributes of speech and natural language production. To date, the majority of research has been cross-sectional, relying mostly on data from structured interactions and restricted to textual versus acoustic analyses. METHODS: In a sample of 71 older (mean age 83.3, SD 7.0 years) community-dwelling adults who completed qualitative interviews and cognitive testing, we investigated the performance of both acoustic and psycholinguistic features associated with cognitive deficits contemporaneously and at a 1-2 years follow up (mean follow-up time 512.3, SD 84.5 days). RESULTS: Combined acoustic and psycholinguistic features achieved high performance (F1-scores 0.73-0.86) and sensitivity (up to 0.90) in estimating cognitive deficits across multiple domains. Performance remained high when acoustic and psycholinguistic features were used to predict follow-up cognitive performance. The psycholinguistic features that were most successful at classifying high cognitive impairment reflected vocabulary richness, the quantity of speech produced, and the fragmentation of speech, whereas the analogous top-ranked acoustic features reflected breathing and nonverbal vocalizations such as giggles or laughter. CONCLUSIONS: These results suggest that both acoustic and psycholinguistic features extracted from qualitative interviews may be reliable markers of cognitive deficits in late life.

Using data from Vietnamese-origin older immigrants/refugees in the Houston, Texas area, we assessed their overall health, chronic conditions, disability, depressive symptoms, and cognitive impairment, and examined the association between their chronic conditions and disability by comorbidity clusters. The mean age of the sample was 76 years old. The majority were married in fair/poor health with several chronic conditions and disabilities and lived with families in low-income households. Hypertension and arthritis were the most common health conditions, but cognitive impairment had the most significant impact on their disability. They experienced similar health conditions to other older Americans but had higher rates of depressive symptoms and cognitive impairment possibly due to cultural factors that may have delayed mental health treatment. Culturally and linguistically tailored services created by policymakers, healthcare professionals, and local social service agencies are recommended for the well-being of immigrants/refugees who migrated to the U.S. for a better life.

Cognitive impairment in focal cerebellar disorders has been widely recognized and is described as cerebellar cognitive affective syndrome (CCAS). However, the relationship between CCAS and crossed cerebello-cerebral diaschisis (CCD) has rarely been discussed. The present report describes the uncommon phenomenon of CCD in two cases with isolated cerebellar infarction, and discuss its contribution to cognitive impairment. Cognitive performance was examined using the CCAS scale and a battery of neuropsychological assessments. Moreover, the relative distribution of cerebral and cerebellar blood flow was measured using three-dimensional arterial spin labeling imaging. Case 1 showed deficits in general cognition and had impaired language, episodic memory, and executive function. Case 2 showed deficits in general cognition at baseline, and cognitive deterioration of visuospatial abilities, language, episodic memory, and executive function was observed at the 3-month follow-up. Both cases met the diagnosis criteria of CCAS. Reduced cerebral blood flow was observed in the cerebral hemisphere contralateral to the cerebellar infarction at baseline in Case 1, and at the 3-month follow-up in Case 2. The present report describes cognitive decline after isolated cerebellar infarction in combination with contralateral cerebral hypoperfusion, as measured using quantitative arterial spin labeling. One possible mechanism involves the functional depression of cerebello-cerebral pathways.

This study explored the acute effects of different running intensities on cognitive and motor performances in individuals with intellectual disability (ID). An ID group (age, M = 15.25 years, SD = 2.76) and a control group without ID (age, M = 15.11 years, SD = 1.54) performed visual simple and choice reaction times, auditory simple reaction time, and finger tapping tests before and after running at low or moderate intensity (30% and 60% of heart rate reserve [HRR], respectively). Visual simple reaction time values decreased (p <.001) after both intensities at all time points with higher (p =.007) extend after the 60% HRR intensity for both groups. After both intensities, the VCRT decreased (p <.001) in the ID group at all time points compared with preexercise (Pre-EX) while, in the control group, these values decreased (p <.001) only immediately (IM-EX) and after 10 min (Post-10) of exercise cessation. Compared withs Pre-EX, in the ID group, the auditory simple reaction time values decreased (p <.001) at all time points after the 30% HHR intensity whereas, after the 60% HRR, these values decreased only at IM-EX (p <.001), Post-10 (p =.001) and Post-20 (p <.001). In the control group, auditory simple reaction time values decreased (p =.002) only after the 30% HRR intensity at IM-EX. The finger tapping test increased at IM-EX (p <.001) and at Post-20 (p =.001) compared to Pre-EX in both groups only after the 30% HHR intensity and for the dominant hand. The effect of physical exercise on cognitive performances in individuals with ID seems to depend on the cognitive test type as well as the exercise intensity. [ABSTRACT FROM AUTHOR]

Background and objectivesTo investigate the associations between self-reported visual functioning (VF) and hearing functioning with cognition in the Hispanic/Latino population.Research design and methodsWe utilized data from the Miami Ocular Study of Latinos ancillary study to Hispanic Community Health Study/Study of Latinos with 1,056 participants aged 45 and older. The outcomes were cognitive performances assessed by the Digit Symbol Substitution Test (DSST), Word Fluency, Brief-Spanish English Verbal Learning Test-recall (B-SEVLT recall), words recalled over 3 trials, and the Six-Item Screener. VF was measured by National Eye Institute Visual Function Questionnaire (NEI-VFQ), and hearing function was measured by Hearing Handicap Inventory Screening Questionnaire for Adults and Elderly (HHIA/E-S). Multiple regressions were performed for each cognitive outcome while controlling for covariates and complex sampling design.ResultsNEI-VFQ was associated with 3 of the 5 cognitive outcomes. A 4-point NEI-VFQ score difference was associated with a 0.56-point difference in DSST (standard error [SE] = 0.27, p

BACKGROUND: DATATOP was a study of early Parkinsons disease (PD) conducted in the 1980 s, before mandatory folic acid fortification in the United States. Our analysis of its baseline serum samples revealed a geometric mean vitamin B12 of 369 pg/mL and homocysteine (tHcy) of 9.5μmol/l. We also found that low B12 predicted greater worsening of ambulatory capacity (AC) and elevated tHcy (>15μmol/L) predicted greater declines in cognitive function. OBJECTIVE: We sought to measure B12 and tHcy in contemporary trial participants with early PD who had not started dopaminergic treatment and to determine whether these analytes were associated with clinical progression. METHODS: We measured B12 and tHcy from baseline and end-of-study blood samples from three recent clinical trials. RESULTS: Baseline geometric mean B12 levels for these studies ranged from 484- 618 pg/ml and for tHcy ranged from 7.4- 10μmol/L. Use of B12-containing supplements ranged from 41- 61%, and those taking supplements had higher B12 and lower tHcy. Those who began levodopa, but were not taking B12-supplements, had greater end-of-study tHcy. There was no association of baseline tHcy > 15μmol/L with annualized change in Montreal Cognitive Assessment and no association of baseline B12 tertiles with change in AC. CONCLUSIONS: In these longitudinal trials, B12 levels were higher than for DATATOP, due in large part to increased B12-supplement intake, while tHcy levels were similar. Initiation of levodopa was associated with increases of tHcy in those not taking a B12-containing supplement. These smaller studies did not replicate prior findings of low B12 and elevated tHcy with features of progression, possibly due to higher baseline B12.

BackgroundFrontotemporal lobar degeneration (FTLD) is a leading cause of dementia in individuals aged

BACKGROUND: Although effective antiretroviral therapy (ART) has improved the life expectancy of people with HIV (PWH), the prevalence of milder forms of HIV-associated neurocognitive disorders (HAND) persist, and it is associated with systemic and neuro-inflammatory processes that could impact other organ systems. However, the complex signaling mechanisms between the bone-kidney systems and the brain in HAND remain unknown. Extracellular vesicles (EVs) play a potential role in inter-organ communication and are involved in regulating cell activity in distant tissues. In this study, we examined whether levels of EVs from bone-and kidney-related cells associate with cognitive dysfunction and explored the relationship between kidney-bone EV axis in PWH experiencing cognitive deficits. METHODS: EV subtypes were characterized in plasma from 61 PWH with either cognitive impairment (CI, n = 53) or normal cognition (NC, n = 8) based on the American Academy of Neurology criteria for HIV-associated dementia (HAD, n = 11), minor cognitive motor disorder (MCMD, n = 25) or asymptomatic neurocognitive impairment (ANI, n = 17) by spectral flow cytometry. EVs were profiled with markers reflecting bone and kidney cell origin. A support vector machine learning-based model was employed for analyses of EV phenotypes to predict the cognitive dysfunction. RESULTS: Plasma-EVs expressing osteocalcin, sclerostin, and nephrin were significantly higher in the cognitive impairment group compared to the normal cognition group. EVs bearing kidney cell markers correlated significantly with bone-derived EVs. A machine learning-based model, comprised of osteocalcin+, nephrin+, and CD24+ EVs predicted cognitive impairment in PWH on ART. CONCLUSION: Our study reveals that neurocognitive impairment in PWH is associated with increased levels of plasma EVs enriched with the bone markers osteocalcin and sclerostin and the kidney marker nephrin, suggesting that these EV subtypes may be novel candidate biomarkers for disease-spanning neurocognitive dysfunction. Moreover, the relationship between bone-derived EVs with kidney-derived EVs may suggest their role in mediating inter-organ crosstalk in the pathogenesis of HIV-associated cognitive impairment.

BACKGROUND: Between 29% and 67% of neuromyelitis optica spectrum disorder patients have cognitive alterations. OBJECTIVE: To assess the frequency of cognitive impairment in patients with neuromyelitis optica spectrum disorder in Mexico using the Brief International Cognitive Assessment for Multiple Sclerosis. METHODS: We evaluated 40 neuromyelitis optica spectrum disorder patients and 40 healthy controls from Mexico. RESULTS: 28 (70.0%) patients with neuromyelitis optica spectrum disorder had cognitive impairment in two or more cognitive domains. Student´s T test showed statistically poor performance by neuromyelitis optica spectrum disorder patients compared to healthy controls on all three neuropsychological test scores. This significant difference was observed on the Symbols Digit Modalities Test (t = 8.875; p ≤ 0.001); California Verbal Learning Test-II memory (t = 10.418; p ≤ 0.001); and Brief Visuospatial Memory Test Revised (t = 6.123; p ≤ 0.001). CONCLUSIONS: This study showed that 70% of neuromyelitis optica spectrum disorder patients exhibited cognitive impairment in two or more cognitive domains. Determining the frequency of cognitive impairment will guide the decision of Neuropsychologists in planning cognitive rehabilitation across various domains.

As the United States' (US) elderly population becomes increasingly diverse, it is imperative that research studies address cognitive health in diverse populations of older Americans. White Matter Hyperintensities (WMH) are useful imaging findings that can be studied in elderly individuals and have been linked to an increased risk of neurological conditions, such as stroke, cognitive impairment, and dementia. We performed a systematic review of literature using PubMed sources to compile all the studies that investigated the prevalence of ethnic and racial differences of WMH burden amongst diverse groups in the US. We identified 23 unique articles that utilized 16 distinct cohorts of which 94 % were prospective, longitudinal studies that included community-based and family-based populations. The overall results were heterogenous in all aspects of data collection and analysis, limiting our ability to run meta-analyses and draw definitive conclusions. General observations suggest increased vascular risk on African American populations, contributing to greater WMH burden in that population. Overall, the findings of this study indicate a need for a standardized approach to investigating WMH in efforts to measure its clinical impact on diverse populations.

BackgroundAimsMethods and procedureResultsConclusionsDescription tasks are used to evaluate and investigate the production abilities of people with language impairments such as aphasia.The goal of the present study is to investigate the production abilities of Catalan-speaking individuals with aphasia (IWA), as well as a smaller sample of individuals with cognitive impairment (IWCI), in comparison with those of healthy controls. A second goal is to evaluate whether the scoring system of the Catalan version of the CAT (CAT-CAT) is helpful to discriminate different patterns of language impairment.In the study, 109 control subjects, 20 IWA and 4 IWCI were asked to orally describe a picture from the CAT-CAT. The scoring method consisted in a closed-rating system that evaluates productivity, discourse efficiency, fluency, grammatical complexity and grammaticality.The results show that the overall scores of the control subjects were significantly higher than those of the experimental groups; the difference between the two experimental groups was not significant. Yet, the group of IWA showed greater intersubject variability than the group of IWCI. Also, the IWA were consistently worse in fluency, grammaticality and grammatical complexity than the IWCI, which indicated a different pattern of performance between the two groups.Our findings therefore show that the oral picture description of the CAT-CAT is sensitive to the language impairment of subjects with aphasia and cognitive impairment. Moreover, the rating system put forward allows us to uncover different patterns of language impairment, since it includes variables to evaluate separately content and discourse efficiency on the one hand, and grammatical features on the other hand. [ABSTRACT FROM AUTHOR]

[Display omitted] • Significant hippocampal volume reduction found in MCI and AD patients. • No causal link between hippocampal volume reduction and Alzheimer's disease. • Subfield-specific hippocampal changes in MCI advance understanding of AD. This study investigates the association between cognitive dysfunction and hippocampal volumes in Alzheimer's Disease (AD) and Mild Cognitive Impairment (MCI) using Mendelian randomization. A meta -analysis of 503 healthy controls, 562 MCI patients, and 389 CE patients revealed significant reductions in hippocampal and subregion volumes in MCI and AD compared to controls. While various subregions showed volume reductions, no causal relationship between hippocampal volume and AD was established through Mendelian randomization analysis. In conclusion, significant volume reductions were observed in MCI and AD patients, highlighting the complexity of the relationship between hippocampal volume and cognitive impairment. [ABSTRACT FROM AUTHOR]

Neuronal damage in the hippocampus induced by high glucose has been shown to promote the onset and development of cognitive impairment in diabetes, but the underlying molecular mechanism remains unclear. Guided by single-cell RNA sequencing, we here report that high glucose increases O-GlcNAcylation of Bmal1 in hippocampal neurons. This glycosylation promotes the binding of Clock to Bmal1, resulting in the expression of transcription factor Bhlhe41 and its target Dnajb4. Upregulated Dnajb4 in turn leads to ubiquitination and degradation of the mitochondrial Na + /Ca2+ exchanger NCLX, thereby inducing mitochondrial calcium overload that causes neuronal damage and cognitive impairment in mice. Notably, Bhlhe41 downregulation or treatment with a short peptide that specifically blocks O-GlcNAcylation of Bmal1 on Ser424 mitigated these adverse effects in diabetic mouse models. These data highlight the crucial role of O-GlcNAcylation in circadian clock gene expression and may facilitate the design of targeted therapies for diabetes-associated cognitive impairment. Synopsis: The molecular mechanism of high-glucose-induced cognitive impairment in diabetes remains unclear. This work demonstrates that high glucose levels increase Bmal1 O-GlcNAcylation and cause mitochondrial calcium overload and neuronal damage via a Bhlhe41/Dnajb4/NCLX signaling pathway. High- glucose-mediated Bmal1 O-GlcNAcylation upregulates expression of Bhlhe41 and Dnajb4, which promote ubiquitination and degradation of NCLX in hippocampal neurons. Decreased NCLX expression in high-glucose conditions promotes mitochondrial calcium overload and subsequent hippocampal neuron damage. A short synthetic peptide, S424-pe, protects against high-glucose-induced neuronal apoptosis and cognitive dysfunction in mice by inhibiting Bmal1 S424 O-GlcNAcylation. High-glucose-mediated Bmal1-OGlcNAcylation impairs cognitive function in diabetic mice by inducing mitochondrial calcium overload and neuronal damage. [ABSTRACT FROM AUTHOR]

AbstractAimMethodsResultsConclusionsTo investigate the influence of cognitive functions on the effectiveness of Lee Silverman Voice Treatment (LSVT)® BIG therapy on motor symptoms, gait speed, activities of daily living (ADLs), and quality of life (QOL) in people with Parkinson’s disease (PD).This retrospective, single-center cohort study included 20 people with PD (PwPD) with mild cognitive impairment (PD-MCI group) or without (PD-NC group) (n = 10 each).In the PD-NC group, all assessments improved significantly. Similarly, the PD-MCI group showed significant improvements in the total Movement Disorder Society‐sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part III, 10-meter walking test, and total MDS-UPDRS Part II. However, the Parkinson’s Disease Questionnaire summary index showed a trend toward improvement that did not reach statistical significance.LSVT® BIG therapy may improve motor symptoms, gait speed, and ADLs in PwPD, regardless of the presence or absence of MCI. [ABSTRACT FROM AUTHOR]

Patients with Duchenne muscular dystrophy (DMD) commonly show specific cognitive deficits in addition to a severe muscle impairment caused by the absence of dystrophin expression in skeletal muscle. These cognitive deficits have been related to the absence of dystrophin in specific regions of the central nervous system, notably cerebellar Purkinje cells (PCs). Dystrophin has recently been involved in GABAA receptors clustering at postsynaptic densities, and its absence, by disrupting this clustering, leads to decreased inhibitory input to PC. We performed an in vivo electrophysiological study of the dystrophin‐deficient muscular dystrophy X‐linked (mdx) mouse model of DMD to compare PC firing and local field potential (LFP) in alert mdx and control C57Bl/10 mice. We found that the absence of dystrophin is associated with altered PC firing and the emergence of fast (~160–200 Hz) LFP oscillations in the cerebellar cortex of alert mdx mice. These abnormalities were not related to the disrupted expression of calcium‐binding proteins in cerebellar PC. We also demonstrate that cerebellar long‐term depression is altered in alert mdx mice. Finally, mdx mice displayed a force weakness, mild impairment of motor coordination and balance during behavioural tests. These findings demonstrate the existence of cerebellar dysfunction in mdx mice. A similar cerebellar dysfunction may contribute to the cognitive deficits observed in patients with DMD. [ABSTRACT FROM AUTHOR]

Background: Breast cancer patients often experience cognitive impairment as a complication during treatment, which seriously affects their quality of life. This study aimed to assess the risk factors associated with cognitive impairment in breast cancer patients and to construct and validate a nomogram model to predict cognitive impairment in this population. Methods: In this study, we used a convenience sampling method to select 423 breast cancer patients who attended the Department of Breast Surgery at the First Hospital of Jinzhou Medical University from September 2023 to March 2024. We analyzed these patients' cognitive impairment risk factors through LASSO regression and logistic regression analysis to develop a predictive model. The model was evaluated using the area under the curve (AUC) from the receiver operating characteristic (ROC) curve and the calibration curve and decision curve analysis. Results: This study found a prevalence of cognitive impairment of 19.62% among breast cancer patients. A nomogram model was developed based on six influencing factors: age, educational level, pathological type, treatment program, emotional state, and fatigue. The area under the curve (AUC) for the model's training and validation groups was 0.944 and 0.931, respectively. The model calibration curves showed a high degree of consistency, and the decision curve analysis (DCA) indicated good clinical applicability of the model. Conclusions: This nomogram demonstrates good discrimination, calibration, and clinical applicability, making it a more intuitive predictor of the risk of cognitive impairment in breast cancer patients. [ABSTRACT FROM AUTHOR]

AbstractCancer-related cognitive impairment (CRCI) is a significant issue commonly observed following chemotherapy treatment. The study aimed to investigate the changes in cognitive function and their association with IL-6, IL-1β, and IL-10 levels before and after R-CHOP chemotherapy over six cycles. Seventy chemotherapy naïve, newly diagnosed lymphoma patients were enrolled. Cognitive functions and inflammatory cytokines were assessed at baseline (TP1), after 3rd cycle (TP2), and after 6th cycle (TP3). Patients, with mean age of 44.17 ± 13.67 years, showed significantly increased levels of IL-6 and IL-1β and decreased IL-10 levels over time (p < .001). On the Montreal Cognitive Assessment (MoCA), scores of domains such as executive functioning (p = .002), attention (p < .001), language (p < .001), recall (p = .005), and orientation (p < .001) significantly decreased post six cycles of R-CHOP chemotherapy. Correlation analysis at TP2 indicated a positive association between elevated IL-6 levels with a decrease in MoCA scores indicating a decline in cognitive function (ρ = 0.68, p < .001). At TP3, no association of MoCA scores with IL-6 and IL-1β was observed. Decreased IL-10 levels showed a weak association with decreased MoCA scores at TP2 and TP3 (ρ = 0.2, p = .09; for TP3, ρ = 0.16, p = .17), but this was not significant. In summary, the findings of the present study highlight significant cognitive decline and changes in inflammatory cytokine levels following six cycles of R-CHOP. Objective cognitive assessments may be done to detect CRCI in patients treated with R-CHOP. [ABSTRACT FROM AUTHOR]

Given the prevalence of cognitive impairment in older adults and its frequent misdiagnosis or delayed diagnosis, non-pharmacological interventions have been proposed as solutions, which include cognitive training, prevention or risk reduction of dementia using virtual reality (VR) technology. This study aimed to investigate the effects of a virtual reality cognitive-motor training intervention (VRCMTI) on improving cognitive and physical function in older adults with cognitive impairment. We co-designed the VRCMTI system with multiple stakeholders by organizing symposiums and conducting pilot evaluations. The VRCMTI consisted of three virtual cognitive tasks and three upper limb movement tasks focused on improving working memory, spatial cognition, attention shifting, executive control, joint flexibility, and coordination. One hour of brain cognition and upper limb motor training was performed each week during the 12-week intervention. Sixty older adults were included in the study and randomly assigned to either the VR group or the control group. Participants in the control group received usual care and would not undergo any intervention training. Task independence, accuracy and time were measured during each session. The results showed that the VR group significantly improved global cognitive ability scores compared to the control group, especially in attention and verbal cognition. In addition, older adults in the VR group also showed significant improvements in upper limb motor skills, driven primarily by movement quality and processing speed. The findings suggest that VRCMTI could improve cognitive function and enhance motor performance. When implemented with routine health care for older adults, this practical and effective intervention may be an appropriate complementary strategy for maintaining cognitive health and preventing motor deterioration. [ABSTRACT FROM AUTHOR]

Approximately 50% of patients with chronic neuropathic pain experience cognitive impairment, which negatively impacts their quality of life. The cannabinoid type 2 receptor (CB2R) may be involved in hippocampal cognitive processes. However, its role in chronic neuropathic pain‐induced cognitive impairment remains elusive. Spared nerve injury (SNI) was used to induce chronic neuropathic pain in rats, while the novel‐object recognition test and the Y‐maze test were employed to assess cognitive function. Immunofluorescence, western blotting, and stereotaxic hippocampal microinjection were utilized to elucidate the potential mechanisms. We observed a reduction in mechanical pain threshold and cognitive impairment in SNI rats. This was accompanied by a tendency for hippocampal microglia to adopt pro‐inflammatory functions. Notably, no changes were detected in CB2R expression. However, downregulation of the endogenous ligands AEA and 2‐AG was evident. Hippocampal microinjection of a CB2R agonist mitigated cognitive impairment in SNI rats, which correlated with a tendency for microglia to adopt anti‐inflammatory functions. Additionally, SNI‐induced activation of the p‐ERK/NFκB pathway in the hippocampus. Activation of CB2R reversed this process by upregulating DUSP6 expression in microglia. The effects elicited by CB2R activation could be inhibited through the downregulation of microglial DUSP6 via hippocampal adeno‐associated virus (AAV) microinjection. Conversely, overexpression of hippocampal DUSP6 using AAV ameliorated the cognitive deficits observed in SNI rats, which remained unaffected by the administration of a CB2R antagonist. Our findings demonstrate that activation of hippocampal CB2R can mitigate chronic neuropathic pain‐induced cognitive impairment through the modulation of the DUSP6/ERK/NFκB pathway. [ABSTRACT FROM AUTHOR]

Background and purpose Methods Results Conclusions Affective disturbances and cognitive impairment are common sequelae of intracerebral hemorrhage (ICH), yet predictive models for these outcomes remain limited, especially for spontaneous supratentorial ICH with small hematomas (<30 mL). The aim of this study was to investigate predictors of affective disturbances and cognitive impairment following small spontaneous supratentorial intracerebral hemorrhage.We retrospectively analyzed 1692 patients with spontaneous supratentorial ICH between January 2018 and December 2020 at the First Affiliated Hospital of Harbin Medical University. Of these, 1563 patients completed a median follow‐up of 3.5 years. Cognitive function was evaluated using the modified Telephone Interview for Cognitive Status, and affective disturbances using the Hamilton Depression Scale and the Hamilton Anxiety Scale. Restricted cubic spline analyses were employed to examine the relationships between predictors and outcomes.In this cohort, 58.5% had cognitive impairment, 52.8% reported depressive symptoms, and 39.4% exhibited anxiety symptoms. Logistic regression models using Boruta's algorithm demonstrated strong predictive capacity, with areas under the curve of 0.82 for cognitive impairment, 0.78 for depressive symptoms, and 0.73 for anxiety symptoms. Hematoma volume was significantly linked to depressive symptoms (odds ratio [OR] 1.56, 95% confidence interval [CI] 1.38–1.76) and inversely to cognitive impairment (OR 0.67, 95% CI 0.59–0.77). Uric acid levels displayed a nonlinear relationship with cognitive impairment (OR 0.70, 95% CI 0.61–0.81). Hospitalization days significantly raised the risk of both depressive (OR 1.16, 95% CI 1.03–1.30) and anxiety symptoms (OR 1.17, 95% CI 1.04–1.31).The logistic regression model, enhanced by Boruta's algorithm, provides a valuable tool for predicting affective disturbances and cognitive impairment after ICH. It facilitates early identification and improves risk assessment for these neuropsychiatric outcomes in patients with small hematomas. [ABSTRACT FROM AUTHOR]

Background: Gastrointestinal symptoms are now detected early in the clinical course of many dementia patients, and studies of the microbiome-gut-brain axis have confirmed bidirectional interactions between the gut and the brain. However, the causal relationship between gut microbiota and cognitive impairment has not been fully established. Therefore, this study conducted a bidirectional Mendelian randomization study to elucidate the potential causal relationship of gut microbiota to cognitive impairment. Objective: Using Mendelian randomization to identify gut flora with a genetic causal effect on the development of cognitive impairment. Methods: This study utilized publicly available genome-wide association study summary data to perform MR analysis, with gut microbiota as the exposure and various cognitive function indicators as well as scores for Alzheimer's disease as outcomes. This study selected single nucleotide polymorphisms as instrumental variables based on p-values, F-statistics, and r2. Bidirectional Mendelian randomization was conducted using methods such as inverse variance weighted, MR-Egger, simple mode, and weighted mode to assess the causal relationship. Concurrently, this study carried out Cochran's Q test, MR-Egger intercept test, and leave-one-out analysis to identify potential heterogeneity and horizontal pleiotropy. Results: This study identified a total of 31 gut microbes that have a causal relationship with cognitive impairment, which include 1 phylum, 4 classes, 3 orders, 2 families, and 21 genera. Conclusions: This study unveiled specific gut microbiota associated with cognitive impairment, offering new insights and approaches for the prevention and treatment of cognitive impairment through gut microbiota such as Bifidobacterium and Ruminococcus gnavus group. [ABSTRACT FROM AUTHOR]

In recent years, several studies have suggested that obesity may play an important role in cognitive impairment. Individuals with cognitive impairment often also exhibit depressive symptoms. This study aimed to explore the association between obesity and cognitive impairment and to elucidate the mediating role of depressive symptoms in this association. Older participants in the U.S. were examined in this cross-sectional study (n = 2391). The WWI was computed as follows: WWI = waist circumference/square root of body weight. The Consortium for Alzheimer's Disease Word Learning (CERAD-WL), the Animal Fluency Test (AFT), and the Digit Symbol Substitution Test (DSST) were used to evaluate cognitive function. Depression symptoms were evaluated with the Patient Health Questionnaire 9 (PHQ-9). Subgroup analysis and multiple logistic regression analysis were utilized to investigate the relationships between the WWI and depressive symptoms and cognitive decline. Threshold effects were computed using a two-segment linear regression model. To ascertain whether depression mediates the relationship between the WWI and cognitive impairment, mediation analysis was also employed. A total of 2391 participants were included, 33.29 % of whom had cognitive impairment. There was a significant correlation between the WWI and depressive symptoms and cognitive function (P < 0.05). With increasing WWI quartiles, the prevalence of cognitive impairment increased (Q1: 27.09 %, Q2: 33.00 %, Q3: 31.44 %, Q4: 41.64 %). It was highly likely that the WWI and cognitive impairment were positively correlated (OR = 1.34, 95 % CI = 1.13, 1.59), and this link was steady across all subgroups (P for trend >0.05). A nonlinear curve with an inflection point of 10.71 connected the WWI and cognitive deterioration. A significant correlation was found between the WWI and cognitive impairment on the left side of the inflection point (OR = 3.58, 95 % CI = 1.57, 8.15). With a 5.4 % mediation rate, mediation analysis revealed that depressive symptoms mediated the relationship between cognitive impairment and the WWI. There was a positive association between the WWI and the incidence of cognitive impairment in older Americans. Among other factors, depressive symptoms slightly mediated the association between the WWI and cognitive impairment. However, large-scale prospective studies are still needed to analyse the interactions between the three factors in depth. • This study explores the Waist-to-Weight Index (WWI) and its link to cognitive impairment, highlighting depression's mediating role. • Higher WWI linked to increased cognitive impairment risk, suggesting abdominal obesity's role in cognitive decline. • Study links abdominal obesity and depression with cognitive impairment, offering insights into prevention strategies. [ABSTRACT FROM AUTHOR]

Background: Cognitive impairment is common in chronic schizophrenia patients. The purpose of this study was to explore the efficacy of Shen-based Qigong Exercise (SBQE) in improving the cognitive impairment of stable schizophrenia patients in rehabilitation wards. Methods: SBQE is derived from the theory of "body-spirit syncretism (xin shen he yi)" in traditional Chinese medicine (TCM) and is extracted from the four traditional Qigong techniques. In this 12-week, randomized, single-blind, controlled study, a total of 40 schizophrenia patients were randomly assigned to either the SBQE group or the control group. The scores for the Scale for the Assessment of Negative Symptoms (SANS) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) were recorded at baseline and week 12, respectively. Results: At week 12, the mean RBANS total score was 84.5 points in the SBQE group and 72.8 points in the control group. The estimated mean difference was − 11.60 points (2-sided 95% CI, -22.41 to -0.79; P = 0.04). This difference was statistically significant (time-by-group interaction effect estimates, F(1,38) = 5.07; P = 0.03). Conclusions: Our preliminary findings indicated that SBQE led to an improvement in cognitive impairment in stable schizophrenia patients in rehabilitation wards. Further research with robust design and larger sample sizes is necessary to validate the effects of SBQE on cognitive function and psychiatric symptoms in schizophrenia, thus providing more substantial evidence for the clinical application of SBQE. Trial registration: ClinicalTrials.gov Identifier: NCT05310955 on 22/02/2022; http://www.chictr.org.cn/ Identifier: ChiCTR2200057373 on 10/03/2022. [ABSTRACT FROM AUTHOR]

Background and purpose Methods Results Conclusions ‘Neurovascular coupling’ (NVC) alterations, assessing the interplay between local cerebral perfusion and neural activity within a given brain region or network, may reflect neurovascular unit impairment in amyotrophic lateral sclerosis (ALS). The aim was to explore NVC as a correlation between the functional connectivity and cerebral blood flow within the large‐scale resting‐state functional magnetic resonance imaging brain networks in a sample of ALS patients compared to healthy controls (HCs).Forty‐eight ALS patients (30 males; mean age 60.64 ± 9.62 years) and 32 HC subjects (14 males; mean age 55.06 ± 16 years) were enrolled and underwent 3 T magnetic resonance imaging. ALS patients were screened by clinical and neuropsychological scales and were retrospectively classified as very fast progressors (VFPs), fast progressors and slow progressors (SPs).Neurovascular coupling reduction within the default mode network (DMN) (p = 0.005) was revealed in ALS patients compared to HCs, observing, for this network, significant NVC differences between VFP and SP groups. Receiver operating characteristic curve analysis showed that impaired NVC in the DMN at baseline best discriminated VFPs and SPs (area under the curve 75%). Significant correlations were found between NVC and the executive (r = 0.40, p = 0.01), memory (r = 0.32, p = 0.04), visuospatial ability (r = 0.40, p = 0.01) and non‐ALS‐specific (r = 0.40, p = 0.01) subscores of the Edinburgh Cognitive and Behavioural ALS Screen.The reduction of brain NVC in the DMN may reflect largely distributed abnormalities of the neurovascular unit. NVC alterations in the DMN could play a role in anticipating a faster clinical progression in ALS patients, aiding patient selection and monitoring during clinical trials. [ABSTRACT FROM AUTHOR]

Background: Eating performance is the functional ability to get food into the mouth and chew/swallow it. Nursing home residents with dementia commonly experience compromised eating performance and subsequent consequences. Prior work examined the association between resident eating performance and their cognitive and functional ability. Yet, the associations between resident eating performance and behavioral and psychological symptoms, psychotropic medication use, and comorbidities are less studied. This study aimed to examine the association between eating performance and cognition, functional ability, behavioral and psychological symptoms, psychotropic medication use, and comorbidities in nursing home residents with dementia. Methods: This was a secondary analysis using baseline data from two randomized controlled trials, testing the impact of Function Focused Care on function and behavioral symptoms in 882 residents with moderate-to-severe dementia (mean age 86.55 years, 71% female, 30% non-white, 68.5% severe dementia) from 67 nursing homes in two states between 2014 and 2020. Eating performance (dependent variable) was measured using the single self-feeding item of Barthel Index. Independent variables included cognitive impairment, functional ability (Barthel Index total score excluding the self-feeding item score), behavioral and psychological symptoms (agitation, depression, resistiveness-to-care), psychotropic medication use (anti-depression, sedative, anti-psychotics, anti-seizure, anti-anxiety), and comorbidities. Results: Nearly 39% of residents were dependent in eating. On average, residents had five documented comorbidities (SD = 3.06, range = 0–12) and were on approximately one psychotropic medication (SD = 1.25, range = 0–5). Eating performance was associated with cognitive impairment (OR = 0.53, 95% CI = 0.35, 0.79, p =.002), functional ability (OR = 1.05, 95% CI = 1.04, 1.06, p <.001), depressive symptoms (OR = 0.94, 95% CI = 0.89, 0.98, p =.007), and anxiolytic use (OR = 0.64, 95% CI = 0.42, 0.99, p =.046). Conclusions: Findings supported that better eating performance was associated with less cognitive impairment, higher functional ability, fewer depressive symptoms, and less anxiolytic use. Targeted interventions to accommodate to cognitive function, optimize functional ability, minimize anxiolytic use, and manage depressive symptoms are encouraged to support eating performance in residents with dementia. [ABSTRACT FROM AUTHOR]

Background: This study aimed to examine the association between the American Heart Association's (AHA) newly revised Life's Essential 8 (LE8) algorithm, designed for assessing cardiovascular health (CVH), and cognitive impairment among older adults in the United States. Methods: This study employed a cross-sectional design, utilizing data from the 2011–2014 National Health and Nutrition Examination Survey to explore the relationship between CVH and cognitive impairment in older adults. CVH scores are assessed based on the AHA definition of the LE8, categorized into three tiers: low (0–49), medium (50–79), and high (80–100). Cognitive impairment is evaluated using three distinct scoring systems: the Consortium to Establish a Registry for Alzheimer's Disease (CERAD), the Animal Fluency Test (AFT), and the Digit Symbol Substitution Test (DSST). The lowest quartile as the cut-off point; below or equal to the lower quartile was considered as low cognitive population, and above the lower quartile was normal population. To analyze the association, multivariable logistic regression and restricted cubic spline (RCS) models were employed. Results: A significant negative correlation exists between the LE8 and cognitive impairment. After adjusting for multiple variables, the odds ratios (OR) for cognitive impairment, as measured by the CERAD, AFT, and DSST, were compared between patients with high and low CVH. The results indicated OR values of 0.60 (95% CI: 0.36–0.98), 0.72 (95% CI: 0.52–0.97), and 0.29 (95% CI: 0.16–0.53) for the CERAD, AFT, and DSST, respectively. Additionally, the RCS curve demonstrated a significant linear relationship between lifestyle factors encapsulated by the LE8 and cognitive impairment. Conclusions: The findings indicate higher adherence to LE8 was associated with lower odds of cognitive impairment. Furthermore, maintaining optimal CVH is crucial in preventing cognitive impairment. [ABSTRACT FROM AUTHOR]

Background: Dysbiosis of gut microbiota (GM) is intricately linked with cognitive impairment and the incidence of traumatic brain injury (TBI) in both animal models and human subjects. However, there is limited understanding of the impact and mechanisms of fecal microbiota transplantation (FMT) on brain and gut barrier function in the treatment of TBI induced by gas explosion (GE). Methods: We have employed FMT technology to establish models of gut microbiota dysbiosis in male rats, and subsequently conducted non-targeted metabolomics and microbiota diversity analysis to explore the bacteria with potential functional roles. Results: Hematoxylin–eosin and transmission electron microscopy revealed that GE induced significant pathological damage and inflammation responses, as well as varying degrees of mitochondrial impairment in neuronal cells in the brains of rats, which was associated with cognitive decline. Furthermore, GE markedly elevated the levels of regulatory T cell (Tregs)-related factors interleukin-10, programmed death 1, and fork head box protein P3 in the brains of rats. Similar changes in these indicators were also observed in the colon; however, these alterations were reversed upon transfer of normal flora into the GE-exposed rats. Combined microbiome and metabolome analysis indicated up-regulation of Clostridium_T and Allobaculum , along with activation of fatty acid biosynthesis after FMT. Correlation network analysis indirectly suggested a causal relationship between FMT and alleviation of GE-induced TBI. FMT improved intestinal structure and up-regulated expression of tight junction proteins Claudin-1, Occludin, and ZO-1, potentially contributing to its protective effects on both brain and gut. Conclusion: Transplantation of gut microbiota from healthy rats significantly enhanced cognitive function in male rats with traumatic brain injury caused by a gas explosion, through the modulation of gut microbiome composition and the improvement of both gut and brain barrier integrity via the gut-brain axis. These findings may offer a scientific foundation for potential clinical interventions targeting gas explosion-induced TBI using FMT. [ABSTRACT FROM AUTHOR]

Background and aim: Traumatic brain injury (TBI) affects brain functions, often leading to a range of cognitive and motor impairments, necessitating effective rehabilitation. It is expedient for physiotherapists to have adequate knowledge, an appropriate attitude, and practice towards managing cognitive and motor impairments in adults with TBI. This study assessed physiotherapists' knowledge, attitudes, and practices of cognitive and motor impairments in adult patients with TBI. Methods: This cross-sectional study involved 75 physiotherapists recruited from 8 hospitals in South-West Nigeria via purposive sampling. A self-developed questionnaire administered via Google Forms® was used to assess the knowledge, attitude, and practice (KAP) of physiotherapists towards cognitive and motor impairments in adult patients with TBI. Descriptive statistics of mean, median, range, percentages, and frequency distribution tables were used in summarizing the KAP, while the association/correlation between KAP scores and selected demographic/profession-related characteristics was also investigated using inferential statistics of the Man-Whitney U, Kruskal Wallis, and Spearman ranked correlation. The level of significance was set at p < 0.05. Results: The mean age of the participants was 28.73 ± 7.093 years, predominantly female (53.3%), with a bachelor's degree in physiotherapy (78.7%), and specializing in neuro-physiotherapy. Most respondents demonstrated knowledge of cognitive 45 (60%) and motor 42 (56%) impairments in adult TBI patients. There was a (rho = 0.259) positive significant correlation (p = 0.025) between the age of the physiotherapist and their knowledge of the management of cognitive and motor impairment in adult patients with TBI. Conclusion: Many physiotherapists in South-West Nigeria demonstrate good knowledge of TBI, with this knowledge increasing with age. This study underscores the importance of continuous educational training for physiotherapists, a consequence of which should be better rehabilitation and functional outcomes for people with TBI. [ABSTRACT FROM AUTHOR]

Diffuse axonal injury (DAI) results in aberrant functional connectivity and is significantly linked to cognitive impairment. Nevertheless, the network mechanisms influencing neurocognitive function following DAI remain unclear. This study aimed to examine the characteristics of static and dynamic functional network connectivity (FNC) in patients with DAI. Resting-state functional magnetic resonance imaging data were collected from 26 patients with DAI and 27 healthy controls. Resting-state networks were extracted using independent component analysis. We evaluated the connectivity strength through spatial maps and static FNC, and then further dynamic properties were identified using a sliding time-window approach and k-means clustering, and investigated their associations with clinical variables. Patients with DAI showed stronger intra-network spatial maps in the default mode network and subcortical network than healthy controls, but static inter-network functional connectivity remained stable. Furthermore, three recurring states for dynamic connectivity were identified in all participants, and state 1 occurred most frequently in patients with DAI and exhibited higher fractional time, and as well as longer mean dwell time, which was positively associated with MMSE scores. Meanwhile, patients with DAI exhibited mostly increased functional connectivity strength of dynamic FNC in all states, particularly within the default mode network and visual network. These findings suggest that patients with DAI are characterized by altered dynamic FNC and temporal properties, which provide distinct complementary information different from static functional connectivity, and new insights into the neural pathophysiology of DAI associated with cognitive impairment. [ABSTRACT FROM AUTHOR]

AbstractPurposeMethodsResultsConclusions\nIMPLICATIONS FOR REHABILITATIONThe aim of this study is to clarify inconsistencies in the literature regarding the neuropsychological impact of chronic pain and determine how pain catastrophizing and pain intensity may explain cognitive impairment.This cross-sectional study involved 30 participants with chronic primary musculoskeletal pain and 30 healthy controls without pain. The instruments used were the Pain Catastrophizing Scale, the Visual Analogue Scale, the Beck Anxiety Inventory, the Beck Depression Inventory–II, the Wisconsin Card Sorting Test, the Stroop Test, and the Working Memory Index of the Wechsler Adult Intelligence Scale.Chronic pain patients showed slight cognitive impairments in selective attention, sustained attention, working memory, problem solving, planning, abstract reasoning, inhibition, and resistance to interference. The data also indicate that higher levels of pain catastrophizing and pain intensity were independently associated with greater cognitive impairment in patients with pain, specifically in attention and executive functioning. Additionally, the interaction between these pain-related variables predicted further cognitive impairment.This research has contributed to establishing the neuropsychological profile of patients with chronic primary musculoskeletal pain and reinforces evidence of the impact of chronic pain on cognition. These findings may help guide the design of programs aimed at improving cognitive performance.Chronic pain has a significant impact on the psychological wellbeing of those who experience it.Chronic pain is associated with cognitive impairment.Patients with chronic pain may benefit from neuropsychological programs that focus on improving cognitive performance. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Eye movement tasks, especially anti‐saccade tasks, have been used to assess cognitive function in patients with neuropsychiatric disorders. Although it has been shown that individuals with cognitive impairment perform worse on anti‐saccades tasks, there is a lack of systematic evaluation of the sensitivity of parameters of anti‐saccades to assess different subtypes of cognitive impairment.A total of 158 participants were enrolled in this study, consisting of 66 men and 92 women, with an average age of 50.2 ± 10 years. The comparison of pro‐saccade reaction time, anti‐saccade reaction time, and error rates in the saccade task between individuals with cognitive impairments and a normal group was conducted. Furthermore, we systematically analyzed the correlations between the performance in neurological function tests (Mini‐Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Stroop) and these anti‐saccade parameters. Especially, the correlation between these parameters and cognitive function in different domains of the MoCA task were also evaluated.The pro‐saccade reaction time, anti‐saccade reaction time and error rate were negatively correlated with the MMSE and MoCA scores (P < 0.001), and positively correlated with the time used in Stroop tasks. Among them, the error rate had the strongest correlation with the performance of MMSE, MoCA and Stroop tasks (MoCA: P < 0.0001, r2 = −0.608; MMSE: P < 0.0001, r2 = −0.344; Stroop: P < 0.0001, r2 = 0.455). Among the seven cognitive domains examined by the MoCA task, error rates had relatively high correlations with visuospatial/executive (P < 0.0001, r2 = −0.4660) and delayed recall (P < 0.0001, r2 = −0.4228) compared to naming, language (P = 0.0004, r2 = −0.0788), attention (P = 0.0004, r2 = −0.0780), abstraction (P < 0.0001, r2 = −0.1515), orientation (P < 0.0001, r2 = −0.1075). Moreover, pro‐saccade reaction time, anti‐saccade reaction time and error rate of people with high MoCA scores were significantly higher than those of people with low MoCA scores, which can be used to identify people with mild cognitive impairment.Our study's results provide valuable clinical evidence supporting the effectiveness of anti‐saccades in assessing cognitive impairment, which is beneficial for screening and timely clinical intervention in individuals with specific cognitive impairment. [ABSTRACT FROM AUTHOR]

Considering the relevance for patients, economics and public health data about the course of the neurological Post-COVID Syndrome (PCS) are urgently needed. In this study 94 PCS patients (73% female, age in median 49 years) were examined in median 9.4 (T1) and for a second time 14 months (T2) after mild to moderate SARS-CoV-2 infection. Mood, sleep quality and health related quality of life (QoL) were evaluated via structured anamnesis and self-report questionnaires; attention, concentration and memory via psychometric tests. 47% of the patients reported an improvement of their symptoms over time, but only 12% full recovery. 4% noticed deterioration and 49% no change. Main disturbances at both time points were fatigue, deficits in concentration and memory. In patients with perceived improvement QoL significantly increased between T1 and T2, although their test performance as well as the fatigue score remained unchanged. In patients with persisting impairment QoL, fatigue scores and psychometric test results did not change significantly. Abnormal psychometric tests were more frequent at both time points in the group without improvement. But, significant fatigue and cognitive impairment persisted for more than 1 year after SARS-CoV-2 infection in both groups. [ABSTRACT FROM AUTHOR]

Background: Facial aging, cognitive impairment, and dementia are all age-related conditions. However, the temporal relation between facial age and future risk of dementia was not systematically examined. Objectives: To investigate the relationship between facial age (both subjective/perceived and objective) and cognitive impairment and/or dementia risk. Methods: The study included 195,329 participants (age ≥ 60 y) from the UK Biobank (UKB) with self-perceived facial age and 612 participants from the Nutrition and Health of Aging Population in China Project (NHAPC) study (age ≥ 56 y) with objective assessment of facial age. Cox proportional hazards model was used to prospectively examine the hazard ratios (HRs) and their 95% confidence intervals (CIs) of self-perceived facial age and dementia risk in the UKB, adjusting for age, sex, education, APOE ε4 allele, and other potential confounders. Linear and logistic regressions were performed to examine the cross-sectional association between facial age (perceived and objective) and cognitive impairment in the UKB and NHAPC, with potential confounders adjusted. Results: During a median follow-up of 12.3 years, 5659 dementia cases were identified in the UKB. The fully-adjusted HRs comparing high vs. low perceived facial age were 1.61 (95% CI, 1.33 ~ 1.96) for dementia (P-trend ≤ 0.001). Subjective facial age and cognitive impairment was also observed in the UKB. In the NHAPC, facial age, as assessed by three objective wrinkle parameters, was associated with higher odds of cognitive impairment (P-trend < 0.05). Specifically, the fully-adjusted OR for cognitive impairment comparing the highest versus the lowest quartiles of crow's feet wrinkles number was 2.48 (95% CI, 1.06 ~ 5.78). Conclusions: High facial age was associated with cognitive impairment, dementia and its subtypes after adjusting for conventional risk factors for dementia. Facial aging may be an indicator of cognitive decline and dementia risk in older adults, which can aid in the early diagnosis and management of age-related conditions. [ABSTRACT FROM AUTHOR]

Egg consumption could reduce the chance of cognitive decline. We aimed to assess this possible protective effect using data from the Birjand longitudinal aging study (BLAS).In this cross-sectional study, the association between number of whole eggs consumed per week and cognitive impairment was assessed on 1352 participants in the context of the first wave of BLAS conducted on September 2018 to April 2019. Six Item Cognitive Impairment Test (6-CIT), Mini-Mental State Examination (MMSE), Verbal Fluency Test (VFT) and abbreviated mental test (AMT) questionnaires were used to assess the cognitive function. Analyses have been conducted using multiple logistic regression.Participants ate an average of 2.4 eggs per week. Older adults with moderate and high egg consumption (2–3 eggs/week and ≥4 eggs/week, respectively) performed better at 6-CIT (OR: 0.61, 95% CI: 0.46; 0.80; and 0.58, 95% CI: 0.41; 0.82), AMT (0.67, 95% CI: 0.52; 0.87; and 0.56, 95% CI: 0.39; 0.80) and all 4 cognitive tests combined (0.47, 95% CI: 0.30; 0.73; and 0.44, 95% CI: 0.24; 0.78). VFT was not associated, and MMSE score was only associated with high egg intake (0.53, 95% CI: 0.38; 0.74). High egg intake was more protective of cognitive decline (≥40%) than the moderate intake (30–40%). The significance of most associations disappeared after adjustment for confounders and covariates.In summary, the findings of this study suggest a potential inverse relationship, displaying an ascending trend, between weekly egg consumption and cognitive function among elderly Iranians. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion Chronic pain may be an important factor influencing cognitive impairment; however, there is limited research on that link in older adults with disabilities. We aimed to determine the association between chronic pain and cognitive impairment in older adults with disabilities.This 24‐month prospective cohort study involved 143 Japanese older adults (≥65 years of age) with long‐term care insurance. Chronic pain was defined as pain persisting for ≥3 months, and cognitive impairment was defined as a Mini‐Mental State Examination score ≤ 23. We employed logistic regression analysis with chronic pain as the independent variable and cognitive impairment as the dependent variable after propensity score matching (PSM).Sixty‐six participants were selected using PSM, and logistic regression analysis showed that chronic pain was significantly associated with cognitive impairment (odds ratio: 4.103, 95% confidence interval: 1.455–11.567, P = 0.008).To prevent cognitive impairment in older adults with disabilities, the management of chronic pain should be considered, as they are related. [ABSTRACT FROM AUTHOR]

Background Aim Study Design Result Conclusion Relevance to Clinical Practice Critically ill patients experience cognitive impairment throughout their intensive care unit trajectory, in the acute phase and the long‐term alike. Cognitive impairment may negatively impact patients' quality of life and rehabilitation outcomes.To provide an overall examination of literature concerning non‐pharmacological interventions that can enhance cognitive functioning in critically ill patients or facilitate their rehabilitation pathway during and after their intensive care unit stay.This study was conducted as an umbrella review. A systematic search was conducted in CINAHL, Embase, PubMed and PsychINFO, including all types of peer‐reviewed research syntheses published between 2008 and 2023. Eligible studies had to describe interventions capable of improving adult patients' cognitive functioning or supporting their cognitive rehabilitation process throughout the intensive care unit trajectory. All eligible research syntheses were screened systematically; those included were critically appraised.Based on 13 research syntheses, this review summarizes rehabilitative interventions that may be delivered during different phases of critical illness and recovery, in relation to content, delivery and timing. Interventions were: (1) cognitive activities and training, (2) mobilization and physical exercises, (3) emotional, psychological and social support and (4) information.Due to limited evidence, no definitive conclusion can be drawn about which type of intervention is most supportive or effective. Additionally, no recommendations can be made about the optimal timing for intervention delivery.Clinicians involved in developing and implementing cognitive rehabilitation measures should consider designing individualized, multicomponent interventions with a focus on content, delivery and timing. [ABSTRACT FROM AUTHOR]

Background: Numerous studies have indicated an obesity paradox in observational research on aging health, where being normal weight or underweight adversely affects cognitive function, while moderate obesity may offer protective benefits. This study aims to investigate the association between body mass index (BMI), waist circumference (WC), hip circumference (HC), waist-to-height ratio (WHtR), waist-to-hip ratio (WHR), abdominal volume index (AVI), and the joint effect of BMI and HC on cognitive impairment in older Chinese people. Methods: A total of 10,579 participants aged 65 years and older from the 2018 Chinese Longitudinal Healthy Longevity Survey (CLHLS) were included in this cross-sectional study. BMI, WC, HC, WHtR, WHR, and AVI were calculated from height, weight, WC, and HC measurements, where weight, WC, and HC were obtained by direct measurement. Mini-Mental State Examination was used to assess cognitive impairment. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated using binary logistic regression. Non-linear correlations were investigated using restricted cubic spline curves. Results: In multivariate logistic regression models fully adjusted for confounding variables, our analyses showed significant negative associations of WC [OR 0.93 (95%CI 0.88–0.98), P =.012], HC [OR 0.92 (95%CI 0.87–0.97), P =.004], lower WHR (Q2) [OR 0.85 (95%CI 0.72-1.00), P =.044], and AVI [OR 0.93 (95%CI 0.88–0.98), P =.011] with cognitive impairment. Nonlinear curve analysis showed that the risk of cognitive impairment was lowest when the BMI was about 25.5 kg/m², suggesting that the optimal BMI for older Chinese people to maintain good cognitive ability may be in the overweight range. In addition, there was a non-linear "N" shaped relationship between HC and cognitive impairment, with HC having the highest risk of cognitive impairment at about 82 cm and the lowest risk at about 101 cm. The joint effects analysis indicated that the lowest risk was observed among those with normal or higher BMI but higher HC compared with participants with normal BMI levels and lower HC levels. Conclusion: In older Chinese people, a low-waisted and high-hip circumference body figure is favorable for cognitive function in older people. It also found a significant association between AVI and cognitive impairment. The joint analysis of BMI and HC suggests that maintaining a normal or higher BMI with a higher HC may be more conducive to maintaining good cognitive function. [ABSTRACT FROM AUTHOR]

Background: There is growing evidence that atrial fibrillation (AF) is a risk factor for cognitive impairment (CI) and dementia in the presence or absence of stroke. The purpose of this study was to explore the mechanism of CI caused by AF. Methods: Eighteen male canines were randomly divided into a sham group, a pacing group, and a pacing + GW4869 group. An experimental model of AF was established by rapid atrial pacing (450 beats/min) for 2 weeks, and the sham group received pacemaker implantation without atrial pacing. The GW4869 group received an intravenous GW4869 injection (0.3 mg/kg, once a day) during pacing. All canines were locally injected with Ad-CD63-RFP in epicardial adipose tissue (EAT) to trace the exosomes. Ultracentrifugation was employed to isolate EAT-derived exosomes, followed by RNA sequencing and quantitative real-time PCR (qRT-PCR) to assess RNA in both exosomes and hippocampal tissue. The miRanda database was used to predict the targeting relationships between miRNA and mRNA, which were further validated by luciferase reporter assays. Western blot analysis was conducted to detect exosomal markers (CD63, CD81, TSG101) in EAT exosomes, while immunofluorescence was used to detect Ad-CD63-RFP signals in both EAT and hippocampal tissues, as well as microglial activation marker IBA-1. To further explore the effects of exosomes on microglial cells, in vitro experiments using brain microvascular endothelial cells (bEnd3) and microglial cells (BV2) were conducted. IBA-1 expression and RNA levels in BV2 cells were analyzed by immunofluorescence and qRT-PCR, respectively. Results: After 14 days of pacing of the canine atrium, compared to the sham group, both the pacing and GW4869 groups exhibited an increased number of AF inductions, along with prolonged AF duration. The fluorescence intensity of Ad-CD63-RFP and the microglial activation marker IBA-1 were markedly greater in the hippocampus. RNA sequencing showed that the differentially expressed gene cfa-miR-22e in EAT exosomes was upregulated, and its target gene IL33 was downregulated in the hippocampus. qRT-PCR showed that the levels of cfa-miR-22e were increased in both EAT exosomes and the hippocampus, while the expression of IL-33, a target of cfa-miR-22e, was decreased in the hippocampus. The administration of GW4869 abolished these effects. The in vitro results from bEnd3 and BV2 cell experiments were consistent with the conclusions drawn from the in vivo studies. Conclusion: Our study indicated that the exosomes secreted by EAT in canines with AF can penetrate the BBB and activate microglia in the hippocampus through the cfa-miR-22e/IL33 signalling pathway. [ABSTRACT FROM AUTHOR]

A considerable proportion of patients with schizophrenia perform below population norms on standardized neuropsychological tests, and the performance of those performing within normal range is lower than predicted based on parental education. Cognitive impairment predates the onset of psychosis, is observed during symptom remission and in non-affected first-degree relatives of patients. At the present time, cognitive deficits are regarded as key features of schizophrenia, important determinants of poor psychosocial outcome and targets for both pharmacological and non-pharmacological treatment strategies. A group of eight key opinion leaders reviewed and discussed latest advances in scientific research and current good clinical practices on assessment, management, and treatment of CIAS. In the present paper they summarize the current evidence, identify main gaps between current knowledge and mental health services clinical practice, and provide practical recommendations to reduce the gap. [ABSTRACT FROM AUTHOR]

Background: Despite antiretroviral treatment (cART), aging people living with HIV (PWH) are more susceptible to neurocognitive impairment (NCI) probably due to synergistic/additive contribution of traditional cerebrovascular risk factors. Specifically, transmigration of inflammatory CD16+ monocytes through the altered blood brain barrier (BBB) may exacerbate cerebral small vessel disease (CSVD), a known cause of vascular cognitive impairment. Methods: PWH on cART (n=108) and age, sex, and Reynold's cardiovascular risk score-matched uninfected individuals (PWoH, n=111) were enrolled. This is a longitudinal observational study but only cross-sectional data from entry visit are reported. Neuropsychological testing and brain magnetic resonance imaging (MRI) were performed. CSVD was diagnosed by Fazekas score ≥1. Flow cytometric analyses of fresh whole blood were conducted to evaluate circulating levels of monocyte subsets (classical, intermediate, and non-classical) and markers of monocyte activation (CCR2, CD40, PSGL-1, TNFR2 and tissue factor). ELISAs were used to measure sCD14, ICAM, and Osteoprotegerin. Two-way analysis of variance (ANOVA), and linear regression models were performed to study the effects of HIV status, CSVD status, and their interaction to outcome variables such as cognitive score. Two-sample t-tests and correlation analyses were performed between and within PWoH with CSVD and PWH with CSVD participants. Results: PWH with CSVD (n=81) had significantly lower total cognitive scores, higher levels of NCMs and soluble CD14 and intracellular adhesion molecule 1 (ICAM-1) as compared to PWoH with CSVD group (n=68). sCD14 and ICAM1 were positively correlated with each other indicating that monocyte and endothelial activation are associated with each other. Cognition was negatively correlated with NCMs, especially in the PWH with CSVD group. Among other blood biomarkers measured, osteoprotegerin levels showed mild negative correlation with cognitive performance in individuals with CSVD irrespective of HIV status. Conclusions: Elevated levels of NCMs may contribute to neuroinflammation, CSVD and subsequent cognitive impairment. This finding is of particular relevance in aging PWH as both HIV and aging are associated with increased levels of NCMs. NCMs may serve as a potential biomarker to address these comorbidities. Further longitudinal studies are needed to evaluate whether changes in NCM levels are associated with changes in CSVD burden and cognitive impairment. [ABSTRACT FROM AUTHOR]

Background: Patients with Alzheimer's disease (AD) often exhibit characteristic clinical manifestations, particularly neuropsychiatric symptoms. Previous studies have shown that white matter hyperintensity (WMH) is strongly associated with AD progression, as well as neuropsychiatric symptoms. The purpose of this study was to investigate the clinical and neuropsychological characteristics of AD patients with WMH. Methods: This retrospective study involved 104 18-fluorodeoxyglucose-positron emission computed tomography (18FDG-PET-CT)-defined AD patients treated at Tianjin Huanhu Hospital from January 2010 to December 2022. Cranial magnetic resonance imaging (MRI) provided semi-quantitative data on brain structure and WMH. Collect and analyze patient clinical data. Neuropsychological assessments were used to evaluate cognitive function and psychobehavioral traits. Results: Among the 104 patients, 66 were in the WMH group (63.5%) and 38 in the non-white matter hyperintensity (non-WMH) group (36.5%). There were no significant differences in gender, age, age of onset, education, BMI, smoking, drinking, diabetes, coronary heart disease, dementia family history, fasting blood glucose, total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) between the two groups. The WMH group showed higher rates of hypertension, homocysteine (Hcy) levels, NPI, and CDR scores as compared to the non-WMH group (p < 0.05). MMSE and MoCA scores were significantly lower in the WMH group (p < 0.05). In the MMSE subitem analysis, patients in the WMH group showed a decrease in attention, recall, and language scores. In the MOCA subitem analysis, WMH patients had lower scores in executive function, naming, attention, language, abstraction, and orientation (p < 0.05). Furthermore, subgroup analysis of NPI showed a higher incidence of delusions, depression, and apathy in the WMH group (p < 0.05). According to the hierarchical analysis of mild, moderate and severe dementia groups, the hypertension, leukoencephalopathy, Hcy level, Fazekas total score, PWMH and DWMH scores in the severe dementia group were significantly higher than those in the mild and moderate dementia groups (p < 0.05). As the disease progresses, more and more patients show increased white matter hyperintensity. Conclusion: White matter lesions are closely correlated with cognitive decline and psychobehavioral symptoms in AD patients, and may be used as an indicator of disease progression. Priority should be given to early screening and prevention of WMH-related risk factors. [ABSTRACT FROM AUTHOR]

Objective: Developmental and epileptic encephalopathies (DEEs) are neurological disorders characterized by developmental impairment and epilepsy. Our study aims to assess disease progression by comparing clinical findings, electroencephalography (EEG), and neuropsychological data from seizure onset to the last follow‐up evaluation. Methods: We retrospectively reviewed patients with genetic DEEs who were followed‐up at the epilepsy unit of Bambino Gesù Children's Hospital, Rome. We collected information regarding gender, family history, genetic variant, age at onset and at last follow‐up, neurological examination, type of seizure, drug resistance, occurrence of status epilepticus, and movement and cognitive and behavioral disorders. We compared EEG background activity, epileptiform abnormalities, and cognitive functions between seizure onset and the last follow‐up evaluation using the McNemar‐Bowker test (α = 5%). Results: A total of 160 patients (94 female) were included. Genetic analysis revealed a spectrum of pathogenic variants, with SCN1A being the most prevalent (25%). The median age at seizure onset and at the last follow‐up was 0.37 (interquartile range [IQR]: 0.09–0.75) and 8.54 years (IQR: 4.32–14.55), respectively. We documented a statistically significant difference in EEG background activity (p =.017) and cognitive impairment (p =.01) from seizure onset to the last follow‐up evaluation. No significant differences were detected for epileptiform abnormalities (p =.2). In addition, high prevalence rates were observed for drug resistance (81.9%), movement disorders (60.6%), behavioral and autism spectrum disorders (45%), neurological deficits (31.3%), and occurrence of status epilepticus (23.1%). Significance: Our study provides evidence that a clinical progression may appear in genetic DEEs, manifesting as development or worsening of cognitive impairment and disruption of EEG background activity. These results highlight the challenging clinical course and the importance of early intervention and personalized care in the management of patients with DEEs. [ABSTRACT FROM AUTHOR]

Sensory deprivation theory is an important hypothesis involving potential pathways between hearing loss and cognitive impairment in patients with presbycusis. The theory suggests that prolonged auditory deprivation in presbycusis, including neural deafferentation, cortical reallocation, and atrophy, causes long‐lasting changes and reorganization in brain structure and function. However, neurophysiological changes underlying the cognition‐ear link have not been explored. In this study, we recruited 98 presbycusis patients and 60 healthy controls and examined the differences between the two groups in gamma‐aminobutyric acid (GABA) and glutamate (Glu) levels in bilateral auditory cortex, excitation–inhibition (E/I) balance (Glu/GABA ratio), dynamic functional network connectivity (dFNC), hearing ability and cognitive performance. Then, correlations with each other were investigated and variables with statistical significance were further analyzed using the PROCESS Macro in SPSS. GABA levels in right auditory cortex and Glu levels in bilateral auditory cortex were lower but E/I balance in right auditory cortex were higher in presbycusis patients compared to healthy controls. Hearing assessments and cognitive performance were worse in presbycusis patients. Three recurring connectivity states were identified after dFNC analysis: State 1 (least frequent, middle‐high dFNC strength with negative functional connectivity), State 2 (high dFNC strength), and State 3 (most frequent, low dFNC strength). The occurrence and dwell time of State 3 were higher, on the other hand, the dwell time of State 2 decreased in patients with presbycusis compared to healthy controls. In patients with presbycusis, worse hearing assessments and cognition were correlated with decreased GABA levels, increased E/I balance, and aberrant dFNC, decreased GABA levels and increased E/I balance were correlated with decreased occurrence and dwell time in State 3. In the mediation model, the fractional windows, as well as dwell time in State 3, mediated the relationship between the E/I balance in right auditory cortex and episodic memory (Auditory Verbal Learning Test, AVLT) in presbycusis. Moreover, in patients with presbycusis, we found that worse hearing loss contribute to lower GABA levels, higher E/I balance, and further impact aberrant dFNC, which caused lower AVLT scores. Overall, the results suggest that a shift in E/I balance in right auditory cortex plays an important role in cognition‐ear link reorganization and provide evidence for sensory deprivation theory, enhancing our understanding the connection between neurophysiological changes and cognitive impairment in presbycusis. In presbycusis patients, E/I balance may serve as a potential neuroimaging marker for exploring and predicting cognitive impairment. [ABSTRACT FROM AUTHOR]

Emerging evidence suggests a broader spectrum of celiac disease (CeD) system involvement, including neurological manifestations. We aimed to conduct a systematic review and meta-analysis of the available evidence from studies assessing the association of cognitive impairment and insomnia with CeD. A total of 259 participants with CeD were included in the studies investigating insomnia and 179 were included in studies investigating cognitive impairment. The overall pooled odds ratio for insomnia in patients with CeD was 1.83 (95% confidence interval, 1.38 to 2.42; I2 =0.00%). The present study provides valuable insights into the available evidence from studies investigating cognitive impairment in patients with CeD and our systematic review and meta-analysis revealed a significant association between CeD and insomnia. [ABSTRACT FROM AUTHOR]

Single-value scores reflecting the deviation from (FADE score) or similarity with (SAME score) prototypical novelty-related and memory-related functional MRI activation patterns in young adults have been proposed as imaging biomarkers of healthy neurocognitive ageing. Here, we tested the utility of these scores as potential diagnostic and prognostic markers in Alzheimer's disease (AD) and risk states like mild cognitive impairment (MCI) or subjective cognitive decline (SCD). To this end, we analysed subsequent memory functional MRI data from individuals with SCD, MCI and AD dementia as well as healthy controls and first-degree relatives of AD dementia patients (AD-rel) who participated in the multi-centre DELCODE study (n = 468). Based on the individual participants' whole-brain functional MRI novelty and subsequent memory responses, we calculated the FADE and SAME scores and assessed their association with AD risk stage, neuropsychological test scores, CSF amyloid positivity and APOE genotype. Memory-based FADE and SAME scores showed a considerably larger deviation from a reference sample of young adults in the MCI and AD dementia groups compared to healthy controls, SCD and AD-rel. In addition, novelty-based scores significantly differed between the MCI and AD dementia groups. Across the entire sample, single-value scores correlated with neuropsychological test performance. The novelty-based SAME score further differed between Aβ-positive and Aβ-negative individuals in SCD and AD-rel, and between ApoE ɛ4 carriers and non-carriers in AD-rel. Hence, FADE and SAME scores are associated with both cognitive performance and individual risk factors for AD. Their potential utility as diagnostic and prognostic biomarkers warrants further exploration, particularly in individuals with SCD and healthy relatives of AD dementia patients. [ABSTRACT FROM AUTHOR]

Cerebral small vessel disease (SVD) is known to contribute to cognitive impairment, apathy and gait dysfunction. Although associations between cognitive impairment and either apathy or gait dysfunction have been shown in SVD, the inter-relations among these three clinical features and their potential common neural basis remain unexplored. The dopaminergic meso-cortical and meso-limbic pathways have been known as the important brain circuits for both cognitive control, emotion regulation and motor function. Here, we investigated the potential inter-relations between cognitive impairment, apathy and gait dysfunction, with a specific focus on determining whether these clinical features are associated with damage to the meso-cortical and meso-limbic pathways in SVD. In this cross-sectional study, we included 213 participants with SVD for whom MRI and comprehensive neurobehavioural assessments were performed. These assessments comprised six clinical measures: processing speed, executive function, memory, apathy (based on the Apathy Evaluation Scale) and gait function (based on the time and steps in the Timed Up and Go Test). We reconstructed five tracts connecting the ventral tegmental area (VTA) and dorsolateral prefrontal cortex (PFC), ventral lateral PFC, medial orbitofrontal cortex, anterior cingulate cortex (ACC) and nucleus accumbens within meso-cortical and meso-limbic pathways using diffusion weighted imaging. The damage along the five tracts was quantified using the free water (FW) and FW-corrected mean diffusivity indices. Furthermore, we explored the inter-correlations among the six clinical measures and identified their common components using principal component analysis (PCA). Linear regression analyses showed that higher FW values of tracts within meso-cortical pathways were related to these clinical measures in cognition, apathy, and gait (all P -corrected values < 0.05). The PCA showed strong inter-associations among these clinical measures and identified a common component wherein all six clinical measures loaded on. Higher FW values of tracts within meso-cortical pathways were related to the PCA-derived common component (all P -corrected values < 0.05). Moreover, FW values of the VTA-ACC tract showed the strongest contribution to the PCA-derived common component over all other neuroimaging features. In conclusion, our study showed that the three clinical features (cognitive impairment, apathy, and gait dysfunction) of SVD are strongly inter-related and that the damage in meso-cortical pathway could be the common neural basis underlying the three features in SVD. These findings advance our understanding of the mechanisms behind these clinical features of SVD and have the potential to inform novel management and intervention strategies for SVD. [ABSTRACT FROM AUTHOR]

Background: Cognitive impairments are common in alcohol use disorder (AUD), but only a few studies have investigated the accuracy of the Montreal Cognitive Assessment (MoCA) in this population. We examined the accuracy and precision of the MoCA in detecting cognitive impairment in a sample of patients with AUD. In addition, we investigated whether the MoCA predicts premature discontinuation from treatment. Method: A sample of 126 persons with AUD undergoing treatment in specialist health services were administered the MoCA and a battery of 12 neuropsychological tests. Five cognitive domains were derived from the reference tests. A composite total score from these tests was used as a reference criterion for determining correct and incorrect classifications for the MoCA. We analyzed the optimal cut‐off score for the MoCA and the accuracy and agreement of classification between the MoCA and the reference tests. Results: Receiver operating characteristic (ROC) curve analyzes yielded an area under the curve (AUC) of 0.77 (95% CI [0.67, 0.87]). Applying 25 as the cut‐off, MoCA sensitivity was 0.77 and specificity 0.62. The PPV was 0.53. The NPV was 0.84. Using a cut‐off score of 24 yielded a lower sensitivity 0.60, but specificity was significantly better i.e., 0.79. PPV was 0.68. The NPV was 0.82. Kappa agreement between MoCA and the reference tests was fair to moderate, 0.38 for the cut‐off of 25, and 0.44 for the cut‐off of 24. MoCA did not predict discontinuation from treatment. Conclusions: Our findings indicate limitations in the classification accuracy of the MoCA in predicting cognitive impairment in AUD. Achieving the right balance between accurately identifying impaired cases without including too many false positives can be challenging. Further, MoCA does not predict discontinuation from treatment. Overall, the results do not support MoCA as a time‐efficient screening instrument. [ABSTRACT FROM AUTHOR]

Among the non-motor symptoms associated with Parkinson's disease (PD), cognitive impairment is one of the most common and disabling. It can occur either early or late during the disease, and it is heterogeneous in terms of its clinical manifestations, such as Subjective Cognitive Dysfunction (SCD), Mild Cognitive Impairment (MCI), and Parkinson's Disease Dementia (PDD). The aim of the present review is to delve deeper into the molecular mechanisms underlying cognitive decline in PD. This is extremely important to delineate the guidelines for the differential diagnosis and prognosis of the dysfunction, to identify the molecular and neuronal mechanisms involved, and to plan therapeutic strategies that can halt cognitive impairment progression. Specifically, the present review will discuss the pathogenetic mechanisms involved in the progression of cognitive impairment in PD, with attention to mitochondria and their contribution to synaptic dysfunction and neuronal deterioration in the brain regions responsible for non-motor manifestations of the disease. [ABSTRACT FROM AUTHOR]