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ObjectiveTo clarify the association of anosmia or constipation with cognitive dysfunction and disease severity in patients with Parkinson’s disease (PD).MethodsNewly diagnosed patients with PD (less than 5 years) without a clinical diagnosis of dementia were included from February 2017 to August 2018. The subjects were further divided into subgroups based on whether anosmia occurred and the grade of constipation. The severity of PD motor symptoms was rated using the Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), and cognitive functions were evaluated by Montreal Cognitive Assessment (MoCA). Statistical analyses including t-tests, chi-square tests, multiple linear regression, and binary logistic regression were used to determine statistical significance.ResultsA total of 107 newly diagnosed PD patients were included in this study. The MoCA score was significantly lower in the anosmia group (p < 0.001). Constipation was associated with impaired olfaction in a post-hoc test. The correlation coefficient between MoCA and UPSIT score was 0.41 (p < 0.001). Total anosmia and age were associated with cognitive dysfunction (MoCA < 26) (odds ratio, 2.63, p = 0.003; 1.10, p < 0.001, respectively). The anosmia group had a higher MDS-UPDRS part 3 score with β coefficient of 7.30 (p = 0.02). Furthermore, grade 3 constipation was associated with a higher MDS-UPDRS total score with β coefficient of 14.88 (p = 0.02).ConclusionsAnosmia but not constipation was associated with cognitive impairment in PD patients. Nevertheless, severe constipation was associated with impaired olfaction and PD disease severity. We suggest that the propagation of α-synuclein from the olfactory route is distinct from the enteric nervous system, but the intercommunication between these two routes is complex.

ObjectiveThis study aimed to investigate the relationship between white matter hyperintensities (WMH) and perivascular spaces (PVS) on magnetic resonance imaging (MRI) with Montreal Cognitive Assessment (MoCA) scores in patients referred for possible lecanemab therapy based on clinical suspicion of Alzheimer’s disease (AD) prior to biomarker confirmation.Materials and methodsIn this retrospective review, 149 consecutive patients with suspected AD between November 2023 and June 2024 who were evaluated for possible lecanemab therapy were identified. All underwent brain MRI and had valid MoCA scores. WMH were graded using the Fazekas scale (0-3). PVS were visually graded (1-4) in the basal ganglia and centrum semiovale on T2-weighted images. Generalized linear models assessed the association between imaging markers and MoCA, adjusting for age, sex, hypertension (HTN), hyperlipidemia (HLD), and diabetes mellitus (DM).ResultsThe mean MoCA score was 19.56, reflecting mild to moderate cognitive impairment. The mean Fazekas score was 1.37, indicating mild to moderate WMH burden, while the mean PVS scores for basal ganglia and centrum semiovale were 1.99 and 2.37, respectively. There is no significant correlation between age and MoCA scores in our patient population. A negative association of -0.1 between the Fazekas score and MoCA score was observed after controlling for the effects of PVS. In contrast, PVS did not significantly correlate with MoCA score.ConclusionIn patients evaluated for possible lecanemab therapy, a higher WMH burden was negatively associated with global cognition, whereas PVS demonstrated no significant relationship with MoCA scores. These findings suggest that WMH may be an imaging marker of vascular pathology in those suspected of AD.

Obstructive Sleep Apnea (OSA) is a chronic condition associated with cognitive impairment and various comorbidities. This prospective study evaluated cognitive deficits in OSA patients and identified clinical factors affecting cognitive function. Seventy-two participants were assessed using polysomnography (PSG) and the Montreal Cognitive Assessment (MoCA). Findings revealed significantly lower MoCA scores in severe OSA patients compared to those with mild or moderate OSA. Severe OSA patients had a median MoCA score of 23.5 (20.0-25.0), indicating more significant cognitive impairment, while those with normal OSA severity had the highest median score of 28.5 (27.8-29.2). Mild and moderate OSA patients had median scores of 26.5 (21.0-28.0) and 25.0 (23.80-26.0), respectively (p < 0.008). Logistic regression showed that ex-smoking status negatively impacted MoCA scores more in the unadjusted model (p = 0.003) than in the adjusted one (p = 0.018). Forced Vital Capacity (FVC) positively correlated with MoCA scores, stronger in the unadjusted model (p < 0.001 vs. p < 0.03). Higher Oxygen Desaturation Index (ODI) correlated with higher MoCA scores while increasing Apnea-Hypopnea Index (AHI) severity correlated with lower MoCA scores in both models. A significant negative correlation was found between age and MoCA score (r = -0.473, p < 0.001), and between MoCA score and AHI (r = -0.350, p < 0.003). This study highlights the need for sensitive cognitive screening tools like MoCA inevaluating OSA patients, linking cognitive impairment closely with OSA severity and other clinical factors.

Cognitive decline in elderly patients with type 2 diabetes is associated with glycated albumin, ratio of Glycated Albumin to glycated hemoglobin, and concentrations of inflammatory and oxidative stress markers

To investigate alterations in resting-state electroencephalogram (EEG) microstates across the cognitive spectrum of Parkinson's disease (PD) and to evaluate their utility as electrophysiological biomarkers of cognitive impairment. Resting-state EEG was recorded using a 19-channel system during a 3-min eyes-closed session in 36 healthy controls (HC), 38 PD patients with normal cognition (PDNC), and 39 PD patients with dementia (PDD). Temporal parameters (duration, occurrence, coverage) of six canonical microstates (A-F) were computed and compared across groups. Correlation analyses were conducted between microstate metrics and Montreal Cognitive Assessment (MoCA) scores. Significant group differences were found in microstate dynamics. The PDD group exhibited a longer mean duration of microstates A, C, and E, and a lower occurrence per second of microstates B and C compared to both the PDNC and HC groups (all P < 0.05). Critically, the duration of microstates A and C showed significant negative correlations with MoCA scores (P < 0.05), while the occurrence of microstates B and C demonstrated positive correlations with MoCA scores (P < 0.05). Specific EEG microstate abnormalities are associated with cognitive status in PD. The prolongation of microstates A and C and the reduced occurrence of microstates B and C are stage-sensitive biomarkers that reflect the severity of cognitive decline, providing novel insights into the neural mechanisms of PD-related cognitive dysfunction.

Background: People with Parkinson's disease (PD) display poorer gait performance when walking under complex conditions than under simple conditions. Screening tests that evaluate gait performance changes under complex walking conditions may be valuable tools for early intervention, especially if allowing for massive data collection.Objectives: To investigate the use of the Goalkeeper Game (GG) to predict impairment in gait performance under complex conditions in people with Parkinson's disease (PPD) and compare its predictive power with the one of the Montreal Cognitive Assessment (MoCA) test.Methods: 74 PPD (HY stages: 23 in stage 1; 31 in stage 2; 20 in stage 3), without dementia (MoCA cut-off 21), tested in ON period with dopaminergic medication were submitted to single individual cognitive/motor evaluation sessions. MoCA and GG were used to assess cognition, and the dynamic gait index (DGI) test was used to assess gait performance under complex condition. GG test resulted in 9 measures extracted via a statistical model. The predictive power of the GG measures and the MoCA score with respect to gait performance, as assessed by DGI, were compared.Results: The predictive models based on GG obtained a better score of prediction (65%) then MoCA (56%) for DGI scores (at a 50% specificity).Conclusion: GG is a novel tool for noninvasive screening that showed a superior predictive power in assessing gait performance under complex condition in people with PD than the well-established MoCa test.

Background:Rapid eye movement (REM) sleep behavior disorder (RBD) and obstructive sleep apnea (OSA) are the most common sleep disorders in Parkinson's disease (PD). The aim of this study was to identify whether RBD could alleviate OSA severity in PD patients and its effect on cognitive impairment.Methods:From February 2014 to May 2017, we recruited 174 PD patients from the Second Affiliated Hospital of Soochow University, all of whom underwent polysomnography (PSG). We collected clinical data, PSG results, and compared information between patients with and without RBD or OSA by analysis of covariance. We also investigated the effect of these sleep disorders on cognitive impairment using linear regression.Results:We grouped participants as follows: PD only (n = 53), PD + OSA (n = 29), PD + RBD (n = 61), and PD + RBD + OSA (n = 31). Minimum oxygen saturation (SaO2) during whole sleep and in REM sleep was higher in PD + RBD + OSA patients than that in PD + OSA patients. PD + RBD patients had worse Mini-Mental Status Examination and Montreal Cognitive Assessment (MoCA) scores than those in the PD group (P < 0.001), especially in visuospatial/executive, attention, and memory functions. The PD + OSA group performed worse than the PD group in the delayed recall domain. After adjusting for age, sex, body mass index, education, disease severity, and other sleep disorders, MoCA was negatively associated with OSA (β = −0.736, P = 0.043) and RBD (β = −2.575,P < 0.001). The severity of RBD (tonic/phasic electromyography activity) and OSA (apnea-hypopnea index/oxygen desaturation index/minimum SaO2) were also associated with MoCA. The adjusted β values of RBD-related parameters were higher than that for OSA.Conclusions:We found that RBD alleviated OSA severity; however, RBD and OSA together exacerbated PD cognitive impairment. Further studies are needed to evaluate whether OSA treatment can improve cognition in PD.

It is established that one of the best predictors of a future diagnosis of Parkinson's disease is a current diagnosis of rapid eye movement behaviour disorder (RBD). In such patients, this provides a unique opportunity to study brain physiology and behavioural motor features of RBD that may precede early-stage Parkinson's disease. Based on prior work in early-stage Parkinson's disease, we aim to determine if the function of corticostriatal and cerebellar regions are impaired in RBD using task-based functional MRI and if structural changes can be detected within the caudate, putamen and substantia nigra in RBD using free-water imaging. To assess motor function, we measured performance on the Purdue Pegboard Test, which is affected in patients with RBD and Parkinson's disease. A cohort of 24 RBD, 39 early-stage Parkinson's disease and 25 controls were investigated. All participants were imaged at 3 Telsa. Individuals performed a unimanual grip force task during functional imaging. Participants also completed scales to assess cognition, sleep and motor symptoms. We found decreased functional activity in both RBD and Parkinson's disease within the motor cortex, caudate, putamen and thalamus compared with controls. There was elevated free-water-corrected fractional anisotropy in the putamen in RBD and Parkinson's disease and elevated free-water in the putamen and posterior substantia nigra in Parkinson's disease compared with controls. Participants with RBD and Parkinson's disease performed significantly worse on all tasks of the Purdue Pegboard Test compared with controls. The both hands task of the Purdue Pegboard Test was most sensitive in distinguishing between groups. A subgroup analysis of early-stage RBD (<2 years diagnosis) confirmed similar findings as those in the larger RBD group. These findings provide new evidence that the putamen is affected in early-stage RBD using both functional and free-water imaging. We also found evidence that the striatum, thalamus and motor cortex have reduced functional activity in early-stage RBD and Parkinson's disease. While the substantia nigra shows elevated free-water in Parkinson's disease, we did not observe this effect in early-stage RBD. These findings point to the corticostriatal and thalamocortical circuits being impaired in RBD patients.

IntroductionThe preoperative evaluation of Parkinson’s Disease (PD) patients for subthalamic nucleus deep brain stimulation (STN-DBS) includes the assessment of the neuropsychological status of the patient. A widely used preoperative test is the Mattis Dementia rating scale (MDRS). However, the Montreal cognitive assessment (MoCA) has also been proven to be a sensitive, time-sparing tool with high diagnostic validity in PD. We evaluate the utility of the MoCA as a preoperative screening test for PD patients undergoing bilateral STN-DBS.MethodsIn this single-centre, retrospective study, we analysed pre- and postoperative assessments of MoCA, MDRS, Movement disorder society-Unified PD Rating Scale-motor examination, PD Questionnaire-39 and levodopa equivalent daily dose. Longitudinal outcome changes were analysed using paired t-test, Pearson’s correlation coefficient, linear regression and CHAID (chi-square automatic interaction detector) regression tree model.ResultsClinical motor and cognitive scores of 59 patients (61.05±7.73 years, 24 females) were analysed. The MoCA, but not the MDRS, identified significant postoperative cognitive decline in PD patients undergoing STN-DBS. The preoperative MoCA score correlated with postoperative quality of life improvement, whereas the MDRS did not. PD patients with a MoCA score ≤ 23 points had a significant decline of quality of life after DBS surgery compared to patients > 23 points.ConclusionThis study identifies the MoCA as an alternative test within the preoperative evaluation of PD patients for the detection of neuropsychological deficits and prediction of the postoperative improvement of quality of life.

Reasoning is the ability to formulate inferences or conclusions from available information. The two major types, deductive and inductive, are thought to rely on distinct cognitive mechanisms and recruit separate brain areas. Neuroimaging studies yield mixed results; some found the left inferior frontal gyrus (IFG) activations for deductive reasoning and the left dorsolateral prefrontal cortex (DLPFC) for inductive reasoning. This assumption was put to the test in the present study. In two double-blinded, sham-controlled experiments, high-definition transcranial direct current stimulation (HD-tDCS) was used to systematically explore the left IFG's and DLPFC's causal role in deductive and inductive reasoning. Participants with no formal training in logic judged deductive and inductive arguments before and after 10 minutes of anodal, cathodal, or sham tDCS of the left IFG (Experiment 1, n = 20) or left DLPFC (Experiment 2, n = 21). Left IFG anodal tDCS impairs reaction times (RTs) for easy categorical (p = < .001) and propositional (p = .025) deductive arguments and the accuracy for easy inductive propositional arguments (p = .003). Meanwhile, regardless of the active stimulation conditions, left DLPFC tDCS shortens RTs (anodal: p = < .001, cathodal: p = .014) and increases accuracy (anodal: p = .029, cathodal: p = .001) for difficult categorical inductive arguments, but decreases accuracy (anodal: p = .027, cathodal: p = < .001) for difficult propositional inductive arguments. The overall results showed a partial dissociation of the left frontal lobe areas subserving the two types of reasoning and argument difficulty-dependent stimulation effects. This study extends knowledge of the neural basis of reasoning and hopefully inspires interventions that could augment reasoning impairments associated with normal aging and brain lesions.

The Montreal Cognitive Assessment (MoCA) score is a convenient and promising tool for estimating alcoholic patients' global cognitive functioning, a major challenge for all specialized alcohol treatment centers. However, whether or not the score should be corrected for education level and whether the proposed cutoff is relevant in patients with alcohol use disorders (AUD) should be determined. We compared the MoCA scores in patients hospitalized for AUD with and without cognitive impairment assessed by a battery of neuropsychological (NP) tests. Sensitivity, specificity, and cutoff of the MoCA score were analyzed using receiver operating characteristic curve analysis. Thirty-one patients with and 25 without cognitive impairment were included in the study. There were 40 men and 16women, with a mean age of 49.5years. The mean uncorrected MoCA score was 23.1±3.3 in those with and 27.0±1.9 in those without cognitive impairment. NP tests were significantly correlated with the MoCA score. Uncorrected MoCA scores identified more than 80% of the patients with a cutoff score equal to 26, to obtain similar accuracy with the corrected score required using a cutoff score equal to 27. Our results confirm that the MoCA test is a convenient and reliable screening tool to measure cognition defects in alcoholic patients. As using the 1-point education adjustment increases the cutoff score by 1 point, it is suggested to use the noncorrected score and the usual cutoff, that is, 26. Being easy to administer and only moderately time-consuming, the MoCA score should be used extensively in addiction treatment centers.

To explore the association between obesity and cognition impairment in patients with moderate-to-severe obstructive sleep apnea-hypopnea syndrome (OSAHS). A total of 425 eligible patients with moderate-to-severe OSAHS were screened for this retrospective study at Sleep Center, Second Affiliated Hospital, Soochow University from January 2008 to January 2013. Based on body mass index (BMI), they were categorized into normal weight (18.5 ≤ BMI<24, n = 67), mild overweight (24 ≤ BMI<26, n = 100), severe overweight (26 ≤ BMI<28, n = 134) and obese (BMI ≥ 28, n = 124) groups. They were examined by overnight polysomnography (PSG). And cognitive functions were assessed by the Montreal Cognitive Assessment (MoCA) questionnaires. MoCA scores, clinical and polysomnographic variables were compared between the groups. And the correlations between MoCA scores and clinical and PSG parameters were further evaluated by stepwise multivariate regression. Two-way analysis of variance (two-way ANOVA) was performed to examine the effects of obesity and OSAHS on MoCA score. The scores of MoCA progressively decreased across the spectrum from mild overweight to obese groups. The highest BMI group (obese group) had the lowest MoCA score (25.45 ± 2.35 vs 26.26 ± 2.01, 26.29 ± 2.60, 26.05 ± 2.51, P = 0.030, 0.010, 0.048). The evaluations of MoCA subdomains further revealed selective reductions. Compare to normal weight group, the score of visuospatial and executive function, memory/delayed recall significant decreased in obese and severe overweight groups (visuospatial and executive function: 4.48 ± 0.63 vs 4.07 ± 0.94, 4.13 ± 1.04, P = 0.022, 0.048; memory/delayed recall: 3.54 ± 0.90 vs 2.77 ± 1.20, 2.87 ± 1.30, P = 0.001, 0.004). Stepwise multivariate regression analysis demonstrated that MoCA scores were correlated significantly with apnea-hypopnea index (AHI), BMI, age and years of education. Two-way ANOVA revealed that both obesity and OSAHS had independent effects on MoCA score (P = 0.004). The interactions between the effect of obesity and OSAHS on cognitive score were insignificant. It indicated that the effect of BMI on cognitive function did not change with AHI. In OSAHS patients, obesity aggravates cognitive impairment independently of AHI. And obesity is one of the most important influencing factors of cognitive function.

BackgroundThe Montreal Cognitive Assessment (MoCA) is a short global cognitive scale, and some studies suggest it is useful for evaluating cognition in patients with Parkinson's disease (PD). However, its accuracy has been questioned in studies involving patients with low education.ObjectiveWe sought to assess whether some of the MoCA subtests contribute to the low accuracy of the test.MethodsWe performed a cross-sectional retrospective analysis of clinical data in a cohort of 71 patients with PD, most with less than 8 years of education. Patients were examined using the MDS-UPDRS, Hoehn and Yahr and the MoCA. The data were analyzed using mainly descriptive statistics.ResultsWe analyzed the data of 66 patients that were not demented according to the clinical evaluation and classified them using the proposed cut-off MoCA scores for diagnosis of MCI and dementia. Thirteen patients (19.7%) were classified as having normal cognition, 24 (36.3%) MCI and 29 (43.9%) dementia. Patients with dementia had longer disease duration (p=0.016) and lower education (p=0.0001). Total MoCA scores had a an almost normal distribution with a wide range of scores and only one maximum score. Performance on the MoCA was highly correlated with education (correlation coefficient=0.66, p=0.0001). At least five of the 10 MoCA subtests showed significant floor effects.ConclusionWe believe that some of the MoCA subtests may be too difficult to be completed by PD patients with low educational level, thus contributing to the test's poor diagnostic accuracy.

IntroductionWe determined the effect of baseline low density lipoprotein (LDL) and triglyceride (TG) concentrations on cognitive decline, in patients with symptomatic high grade intracranial stenosis.MethodsWe analyzed a cohort of stroke patients who had baseline and 4 months follow‐up Montreal Cognitive Assessment (MoCA) scores. MoCA score worsening after 4 months was the outcome of interest, defined as worsening of ≥ 2 points from baseline. Baseline LDL and TG concentrations (mg/dl) were assessed, and univariate and multivariate analysis using logistic regression were performed to identify predictors of worsening MoCA scores.ResultsA total of 349 patients were analyzed. 313 and 315 patients had baseline LDL and TG, respectively. 61 (17%) had a worsening of MoCA scores. The mean baseline LDL was 97.3 (39.1) in the worsening group, compared to 110.6 (44.8) in those with no worsening (p = 0.014). 23% of patients with LDL < 100 had worsening in MoCA score compared to 11% of patients with LDL ≥ 100 (p< 0.006). The mean baseline TG was 145.7 (102.2) in the worsening group, compared to 170.7 (135.4) (p = 0.053). On multivariate analysis, higher age (p = 0.014) and lower baseline LDL (p = 0.046) were predictors of worsening MoCA scores.ConclusionsPatients who did not undergo any worsening MoCA scores had higher LDL and TG levels at baseline, and only older age and lower baseline LDL scores predicted worsening scores at 4 months. Presumably, the patients with high baseline lipid levels were treated more aggressively with dietary modifications and statins, which could have led to cognitive protective effect regardless of serum lipid profile.

Autoimmune epilepsy is an under-recognized condition, and the mechanisms of antibody-mediated epileptogenesis are unknown. The N-methyl-D-aspartate (NMDA) receptor subunit 3 peptide B (NR3B) modulates Mg2+ sensitivity and Ca2+ mobilization of glutamate responses in the central nervous system (CNS). The levels of antibodies against NR3B (NR3B Ab's) in the cerebrospinal fluid (CSF) and the correlations between NR3B Ab's and cognitive comorbidities of epilepsy patients remain unclear. CSF samples were collected from 36 patients with consecutive epilepsy and 17 healthy controls. The levels of NR3B Ab's in the CSF were measured by ELISA. The cognitive function was assessed by Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE). The results showed that the levels of NR3B Ab's were significantly higher in patients with epilepsy than those in the controls (p<0.01). Thirteen of 36 patients had higher levels of NR3B Ab's exceeding mean+ 2SD of all patients, and the scores of MMSE and MoCA of these 13 patients were significantly lower than the other 23 patients and controls (p<0.01; p<0.001). However, there were no significant differences in the scores of MMSE and MoCA between the 23 patients and the controls. Correlation analysis indicated a significant negative correlation between the levels of NR3B Ab's and the scores of MMSE (correlation coefficient: r=-0.543; p<0.01) or the scores of MoCA (correlation coefficient: r=-0.548; p<0.01). We suggest that some patients with epilepsy may have immune process after onset and the presence of NR3B Ab's may be associated with cognitive comorbidities in patients with epilepsy.