Cognitive Function In Parkinson's Disease Research Articles

Cholinergic Basal Forebrain Integrity and Cognition in Parkinson's Disease: A Reappraisal of Magnetic Resonance Imaging Evidence.

Cognitive impairment is a well-recognized and debilitating symptom of Parkinson's disease (PD). Degradation in the cortical cholinergic system is thought to be a key contributor. Both postmortem and in vivo cholinergic positron emission tomography (PET) studies have provided valuable evidence of cholinergic system changes in PD, which are pronounced in PD dementia (PDD). A growing body of literature has employed magnetic resonance imaging (MRI), a noninvasive, more cost-effective alternative to PET, to examine cholinergic system structural changes in PD. This review provides a comprehensive discussion of the methodologies and findings of studies that have focused on the relationship between cholinergic basal forebrain (cBF) integrity, based on T1- and diffusion-weighted MRI, and cognitive function in PD. Nucleus basalis of Meynert (Ch4) volume has been consistently reduced in cognitively impaired PD samples and has shown potential utility as a prognostic indicator for future cognitive decline. However, the extent of structural changes in Ch4, especially in early stages of cognitive decline in PD, remains unclear. In addition, evidence for structural change in anterior cBF regions in PD has not been well established. This review underscores the importance of continued cross-sectional and longitudinal research to elucidate the role of cholinergic dysfunction in the cognitive manifestations of PD. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

GDNF improves the cognitive ability of PD mice by promoting glycosylation and membrane distribution of DAT

The core of clinic treatment of Parkinson's disease (PD) is to enhance dopamine (DA) signaling within the brain. The regulation of dopamine transporter (DAT) is integral to this process. This study aims to explore the regulatory mechanism of glial cell line-derived neurotrophic factor (GDNF) on DAT, thereby gaining a profound understanding its potential value in treating PD. In this study, we investigated the effects of GDNF on both cellular and mouse models of PD, including the glycosylation and membrane transport of DAT detected by immunofluorescence and immunoblotting, DA signal measured by neurotransmitter fiber imaging technology, Golgi morphology observed by electron microscopic, as well as cognitive ability assessed by behavior tests. This study revealed that in animal trials, MPTP-induced Parkinson's Disease (PD) mice exhibited a marked decline in cognitive function. Utilizing ELISA and neurotransmitter fiber imaging techniques, we observed a decrease in dopamine levels and a significant reduction in the intensity of dopamine signal release in the Prefrontal Cortex (PFC) of PD mice induced by MPTP. Intriguingly, these alterations were reversed by Glial Cell Line-Derived Neurotrophic Factor (GDNF). In cellular experiments, following MPP + intervention, there was a decrease in Gly-DAT modification in both the cell membrane and cytoplasm, coupled with an increase in Nongly-DAT expression and aggregation of DAT within the cytoplasm. Conversely, GDNF augmented DAT glycosylation and facilitated its membrane transport in damaged dopaminergic neurons, concurrently reversing the effects of GRASP65 depletion and Golgi fragmentation, thereby reducing the accumulation of DAT in the Golgi apparatus. Furthermore, overexpression of GRASP65 enhanced DAT transport in PD cells and mice, while suppression of GRASP65 attenuated the efficacy of GDNF on DAT. Additionally, GDNF potentiated the reutilization of neurotransmitters by the PFC presynaptic membrane, boosting the effective release of dopamine following a single electrical stimulation, ultimately ameliorating the cognitive impairments in PD mice.Therefore, we propose that GDNF enhances the glycosylation and membrane trafficking of DAT by facilitating the re-aggregation of the Golgi apparatus, thereby amplifying the utilization of DA signals. This ultimately leads to the improvement of cognitive abilities in PD mouse models. Our study illuminates, from a novel angle, the beneficial role of GDNF in augmenting DA utilization and cognitive function in PD, providing fresh insights into its therapeutic potential.

Cognitive function in different motor subtypes of Parkinson's disease: A systematic review protocol.

As the fastest-growing neurological disorder globally, a better understanding of Parkinson's disease (PD) is needed to improve patient outcomes and reduce the increasing economic and healthcare burden associated with the disease. Whilst classified as a movement disorder, this disease is highly heterogeneous, encompassing a broad range of both motor and non-motor symptoms (NMS). Cognitive impairment, presenting as either mild cognitive impairment or PD-dementia, is one of the most prevalent and disabling NMS. To better understand heterogeneity in PD, researchers have sought to identify subtypes of individuals who share similar symptom profiles. To date, this research has predominantly focused on motor subtyping, with many studies comparing these motor subtypes on non-motor outcomes, such as cognitive impairment. However, despite evidence of a motor-cognitive relationship in healthy aging, findings regarding the presence of a motor-cognitive relationship in PD are inconsistent. In our proposed systematic review, we will investigate motor subtyping studies that have evaluated the relationship between motor and cognitive function in PD. We aim to examine what is currently known about the relationship between motor and cognitive impairment in PD and evaluate the state of the field with respect to the subtyping methods and quality of cognitive assessment tools used. Systematic literature searches will be conducted in PubMed, PsycINFO, CINAHL, Scopus, and Web of Science. Results will be synthesized using meta-analysis and, where meta-analysis is not feasible, narrative synthesis. Despite the preponderance of motor subtyping research in PD, our study will be the first to systematically review evidence regarding the association between motor subtypes and cognitive impairment. Understanding the nature of the motor-cognitive relationship in PD may lead to important insights regarding shared underlying disease pathology, which would have significant implications for early diagnosis, prognosis, and treatment of cognitive impairment in PD.

A nomogram based on neuron-specific enolase and substantia nigra hyperechogenicity for identifying cognitive impairment in Parkinson's disease.

One in four individuals with Parkinson's disease (PD) experience cognitive impairment (CI). However, few practical models integrating clinical and neuroimaging biomarkers have been developed to address CI in PD. This study aimed to evaluate the correlation between circulating neuron-specific enolase (NSE) levels, substantia nigra hyperechogenicity (SNH), and cognitive function in PD and to develop a nomogram based on clinical and neuroimaging biomarkers for predicting CI in patients with PD. A total of 385 patients with PD who underwent transcranial sonography (TCS) from January 2021 to December 2022 at Beijing Tiantan Hospital, Capital Medical University, were recruited as the training cohort. For validation, 165 patients with PD treated from January 2023 to December 2023 were enrolled. Data for SNH, plasma NSE, and other clinical measures were collected, and cognitive function was assessed using the Montreal Cognitive Assessment (MoCA). Logistic regression analysis was employed to select potential risk factors and establish a nomogram. The receiver operating characteristic curve and calibration curve were generated to evaluate the performance of the nomogram. Patients with PD exhibiting CI displayed advanced age, elevated Unified PD Rating Scale-III (UPDRS-III) score, an increased percentage of SNH, higher levels of plasma NSE and homocysteine (Hcy), a larger SNH area, and lower education levels compared to PD patients without CI. Gender [odds ratio (OR) =0.561, 95% confidence interval (CI): 0.330-0.954, P=0.03], age (OR =1.039; 95% CI: 1.011-1.066; P=0.005), education level (OR =0.892; 95% CI: 0.842-0.954; P<0.001), UPDRS-III scores (OR =1.026; 95% CI: 1.009-1.043; P=0.003), plasma NSE concentration (OR =1.562; 95% CI: 1.374-1.776; P<0.001), and SNH (OR =0.545; 95% CI: 0.330-0.902; P=0.02) were independent predictors of CI in patients with PD. A nomogram developed using these six factors yielded a moderate discrimination performance with an area under the curve (AUC) of 0.823 (95% CI 0.781-0.864; P<0.001). The calibration curve demonstrated acceptable agreement between predicted outcomes and actual values. Validation further confirmed the reliability of the nomogram, with an AUC of 0.864 (95% CI: 0.805-0.922; P<0.001). The level of NSE in plasma and the SNH assessed by TCS are associated with CI in patients with PD. The proposed nomogram has the potential to facilitate the detection of cognitive decline in individuals with PD.

The Relationship Between Psychosis and Cognitive Function in Parkinson Disease (P4-3.015)

The Relationship Between Psychosis and Cognitive Function in Parkinson Disease (P4-3.015)

MRI index of glymphatic system mediates the influence of locus coeruleus on cognition in Parkinson's disease

IntroductionAlthough locus coeruleus (LC) has been demonstrated to play a critical role in the cognitive function of Parkinson's disease (PD), the underlying mechanism has not been elucidated. The objective was to investigate the relationship among LC degeneration, cognitive performance, and the glymphatic function in PD. MethodsIn this retrospective study, 71 PD subjects (21 with normal cognition; 29 with cognitive impairment (PD-MCI); 21 with dementia (PDD)) and 26 healthy controls were included. All participants underwent neuromelanin-sensitive magnetic resonance imaging (NM-MRI) and diffusion tensor image scanning on a 3.0 T scanner. The brain glymphatic function was measured using diffusion along the perivascular space (ALPS) index, while LC degeneration was estimated using the NM contrast-to-noise ratio of LC (CNRLC). ResultsThe ALPS index was significantly lower in both the whole PD group (P = 0.04) and the PDD subgroup (P = 0.02) when compared to the controls. Similarly, the CNRLC was lower in the whole PD group (P < 0.001) compared to the controls. In the PD group, a positive correlation was found between the ALPS index and both the Montreal Cognitive Assessment (MoCA) score (r = 0.36; P = 0.002) and CNRLC (r = 0.26; P = 0.03). Mediation analysis demonstrated that the ALPS index acted as a significant mediator between CNRLC and the MoCA score in PD subjects. ConclusionThe ALPS index, a neuroimaging marker of glymphatic function, serves as a mediator between LC degeneration and cognitive function in PD.

Sex differences in the association between Body Mass Index and cognitive function in Parkinson disease: a cross-sectional study.

This study utilized a binary logistic regression model to explore the relationship between Body Mass Index (BMI) and cognitive function in Parkinson's disease (PD) patients. In this cross-sectional study, data were obtained from 1,005 Parkinson's patients enrolled in the Parkinson's Progression Markers Initiative (PPMI) from 2010 to 2023, including 378 females and 627 males. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) scale, and the correlation between BMI and cognitive function was determined using binary logistic regression. The median age of enrollment was 63.6 (56.2, 69.6) years old, including 378 (37.6%) females and 627 (62.4%) males. In the final adjusted model, a significant positive correlation was found between BMI and the prevalence of cognitive impairment in females (OR = 1.06, 95% CI = 1.01 ~ 1.12, p = 0.022), while no correlation was found in males (OR = 1.03, 95% CI = 0.99 ~ 1.08, p = 0.165). The results after categorizing BMI indicate that, among females, the risk of cognitive impairment increases for both groups with BMI ≥ 30 kg/m2 and those with 25 ≤ BMI < 30 kg/m2 compared to the reference group with BMI < 25 kg/m2, with a p for trend <0.001 indicating a stable and strong association between BMI and cognitive impairment in females. In males, the results were not significant. The trend of linear fitting was consistent with the above results. In female Parkinson's patients, there is a positive correlation between BMI and cognitive impairment, while no correlation was found in male patients. This study provides new evidence of sex differences in the correlation between BMI and cognitive impairment among Parkinson's patients. The role of sex differences in the relationship between BMI and cognitive impairment should be considered in future research.

Structural changes in the retina and serum HMGB1 levels are associated with decreased cognitive function in patients with Parkinson's disease

BackgroundCognitive impairment is a serious nonmotor symptom in patients with Parkinson's disease (PD). Currently, there are few studies investigating the relationship of serum markers and retinal structural changes with cognitive function in PD. ObjectiveTo investigate the relationship between retinal structural changes, serum high mobility group box-1 (HMGB1) levels and cognitive function and motor symptoms in PD patients. MethodsEighty-nine participants, including 47 PD patients and 42 healthy subjects, were enrolled. PD patients were divided into Parkinson's disease with normal cognitive (PD-NC), Parkinson's disease with mild cognitive impairment (PD-MCI), and Parkinson's disease with dementia (PDD) groups. The motor and nonmotor symptoms of PD patients were evaluated with clinical scale. Serum HMGB1 levels were detected by enzyme-linked immunosorbent assay (ELISA), and ganglion cell-inner plexiform layer complex (GCIPL) thickness changes in the macula were quantitatively analyzed by swept source optical coherence tomography (SS-OCT) in all patients. ResultsCompared with the control group, the macular GCIPL (t = −2.308, P = 0.023) was thinner and serum HMGB1 (z = −2.285, P = 0.022) was increased in PD patients. Macular GCIPL thickness in patients with PD-MCI and PDD were significantly lower than that in PD-NC patients, but there were no significant difference between the PD-MCI and PDD groups. Serum HMGB1 levels in patients with PD-MCI and PDD were significantly higher than those in PD-NC patients, and serum HMGB1 levels in PDD patients were higher than those in PD-MCI patients. Correlation analysis showed that serum HMGB1 levels in PD patients were positively correlated with disease duration, HY stage, UPDRS-I score, UPDRS-III score, and UPDRS total score and negatively correlated with MOCA score. Macular GCIPL thickness was negatively correlated with HY stage and positively correlated with MOCA score, and macular GCIPL thickness was negatively correlated with serum HMGB1 level. Logistic regression analysis showed that elevated serum HMGB1 level, thinner macular GCIPL thickness, and higher HY stage were independent risk factors for Parkinson's disease with cognitive impairment (PD-CI). The areas under the receiver operating characteristic curve (AUC) for the serum HMGB1 level and macular GCIPL thickness-based diagnosis of PD-MCI, PDD and PD-CI based on in patients with PD were 0.786 and 0.825, 0.915 and 0.856, 0.852 and 0.841, respectively. The AUC for the diagnosis of PD-MCI, PDD and PD-CI with serum HMGB1 level and GCIPL thickness combined were 0.869, 0.967 and 0.916, respectively. ConclusionThe macular GCIPL thickness and serum HMGB1 level are potential markers of cognitive impairment in PD patients, and their combination can significantly improve the accuracy of the diagnosis of cognitive impairment in PD.

Pathological Correlates of Cognitive Decline in Parkinson's Disease: From Molecules to Neural Networks.

Parkinson's disease (PD) is a progressive neurodegenerative disorder caused by the death of dopaminergic neurons in the substantia nigra and appearance of protein aggregates (Lewy bodies) consisting predominantly of α-synuclein in neurons. PD is currently recognized as a multisystem disorder characterized by severe motor impairments and various non-motor symptoms. Cognitive decline is one of the most common and worrisome non-motor symptoms. Moderate cognitive impairments (CI) are diagnosed already at the early stages of PD, usually transform into dementia. The main types of CI in PD include executive dysfunction, attention and memory decline, visuospatial impairments, and verbal deficits. According to the published data, the following mechanisms play an essential role demonstrates a crucial importance in the decline of the motor and cognitive functions in PD: (1) changes in the conformational structure of transsynaptic proteins and protein aggregation in presynapses; (2) synaptic transmission impairment; (3) neuroinflammation (pathological activation of the neuroglia); (4) mitochondrial dysfunction and oxidative stress; (5) metabolic disorders (hypometabolism of glucose, dysfunction of glycolipid metabolism; and (6) functional rearrangement of neuronal networks. These changes can lead to the death of dopaminergic cells in the substantia nigra and affect the functioning of other neurotransmitter systems, thus disturbing neuronal networks involved in the transmission of information related to the regulation of motor activity and cognitive functions. Identification of factors causing detrimental changes in PD and methods for their elimination will help in the development of new approaches to the therapy of PD. The goal of this review was to analyze pathological processes that take place in the brain and underlie the onset of cognitive disorders in PD, as well as to describe the impairments of cognitive functions in this disease.

Effects of dietary supplementation with fermented papaya on oxidative stress, symptoms, and microbiome in Parkinson's disease

Background: Oxidative stress, understood as the alteration of the physiological equilibrium between the production of oxygen and nitrogen free radicals and their metabolic neutralization (redox imbalance), is a typical condition of several pathologies, including neurodegenerative ones.In Parkinson's disease (PD), oxidative phenomena typically interest the dopaminergic neurons of mesencephalic substantia nigra. Although it is unlikely that the redox imbalance represents the primary event of neurodegeneration, it is certain that it participates in cellular damage progression.Objectives: Interventions to prevent or reduce the extent of the oxidative stress in PD and the consequent oxidative damage are of crucial importance. With this study, we have evaluated the effects of prolonged treatment with fermented papaya preparation (FPP) on redox imbalance, clinical parameters, and intestinal microbiome of PD patients. Methods: For six months, one group of PD subjects were treated with FPP (n=19, verum) and another with placebo (n=20, control); then, in the following six months, the treatments were exchanged.Several blood biochemical and hematological parameters were measured at the start and at the end of treatments. Among them are some components of antioxidant barriers, free radicals (total peroxides) and biomarkers of oxidative damage on DNA and proteins. To check the effects of FPP treatment on intestinal bacterial flora, we also evaluated the modification of microbiome with regards to the relative amounts of different phyla, families, genera, and species. Furthermore, accurate evaluations were performed on motor symptoms and cognitive functions of patients with validated survey scales to check the effects of FPP treatment on clinical parameters and quality life. Results: Unlike the control group, the level of free radicals in the patients treated with FPP was not increased; the antioxidant barrier was strengthened and oxidative damages on proteins and especially on DNA were decreased. Even clinical features and quality life parameters of these patients have improved. Instead, the results of microbiome were inconclusive as changes resulted seemingly independent Ofelia the treatments.Conclusions: The study demonstrates that FPP may be a valuable aid in counteracting oxidative stress and improve the motor symptoms and cognitive functions in PD. This effect does not seem to depend on increased growth of a particular bacterial phylum because the microbioma composition does not change significantly following the treatment; it cannot be excluded, however, that FPP works otherwise by modifying not the quantity but rather the metabolism of some specific bacterial group or that it has effects on the integrity of the intestinal mucosa. Keywords: Papaya, oxidative stress, Parkinson’s disease, microbiome

Local white matter abnormalities in Parkinson's disease with mild cognitive impairment: Assessed with neurite orientation dispersion and density imaging.

Mild cognitive impairment is a nonmotor complication in Parkinson's disease (PD) that have a high risk of developing dementia. White matter is associated with cognitive function in PD and the alterations may occur before the symptoms of the disease. Previous diffusion tensor imaging (DTI) studies lacked specificity to characterize the concrete contributions of distinct white matter tissue properties. This may lead to inconsistent conclusions about the alteration of white matter microstructure. Here, we used neurite orientation dispersion and density imaging (NODDI) and white matter fiber clustering method to uncover local white matter microstructures in PD with mild cognitive impairment (PD-MCI). This study included 23 PD-MCI and 20 PD with normal cognition (PD-NC) and 21 healthy controls (HC). To probe specific and fine-grained differences, metrics of NODDI and DTI in white matter fiber clusters were evaluated using along-tract analysis. Our results showed that PD-MCI patients had significantly lower neurite density index (NDI) and orientation dispersion index (ODI) in white matter fiber clusters in the prefrontal region. Correlation analysis and receiver operating characteristic (ROC) analysis revealed that the diagnostic performance of NODDI-derived metrics in cingulum bundle (2 clusters) and thalamo-frontal (2 clusters) were superior to DTI metrics. Our study provides a more specific insight to uncover local white matter abnormalities in PD-MCI, which benefit understanding the underlying mechanism of cognitive decline in PD and predicting the disease in advance.

Genetic variation in the dopamine system is associated with mixed-strategy decision-making in patients with Parkinson's disease.

Decision-making during mixed-strategy games requires flexibly adapting choice strategies in response to others' actions and dynamically tracking outcomes. Such decisions involve diverse cognitive processes, including reinforcement learning, which are affected by disruptions to the striatal dopamine system. We therefore investigated how genetic variation in dopamine function affected mixed-strategy decision-making in Parkinson's disease (PD), which involves striatal dopamine pathology. Sixty-six PD patients (ages 49-85, Hoehn and Yahr Stages 1-3) and 22 healthy controls (ages 54-75) competed in a mixed-strategy game where successful performance depended on minimizing choice biases (i.e., flexibly adapting choices trial by trial). Participants also completed a fixed-strategy task that was matched for sensory input, motor outputs and overall reward rate. Factor analyses were used to disentangle cognitive from motor aspects within both tasks. Using a within-subject, multi-centre design, patients were examined on and off dopaminergic therapy, and genetic variation was examined via a multilocus genetic profile score representing the additive effects of three single nucleotide polymorphisms (SNPs) that influence dopamine transmission: rs4680 (COMT Val158 Met), rs6277 (C957T) and rs907094 (encoding DARPP-32). PD and control participants displayed comparable mixed-strategy choice behaviour (overall); however, PD patients with genetic profile scores indicating higher dopamine transmission showed improved performance relative to those with low scores. Exploratory follow-up tests across individual SNPs revealed better performance in individuals with the C957T polymorphism, reflecting higher striatal D2/D3 receptor density. Importantly, genetic variation modulated cognitive aspects of performance, above and beyond motor function, suggesting that genetic variation in dopamine signalling may underlie individual differences in cognitive function in PD.

Cognitive impairment in advanced Parkinson's disease

AbstractCognitive impairment is known to be a non‐motor symptom of Parkinson's disease (PD). Multiple cognitive domains, such as executive, attention, visuoperceptual, and memory functions, are impaired in PD. Various cognitive neural networks should, therefore, be involved in PD. Neural degeneration due to the pathology of Lewy bodies spread to many neural networks, leading to cognitive impairment. Executive dysfunction is mostly related to dopaminergic network disruption, projecting from the nigrostriatal and mesocorticolimbic systems to the prefrontal lobes. This idea was strengthened by the convincing evidence that administrating levodopa can provide beneficial effects for executive functions with improvements in motor symptoms. Frontoparietal cholinergic and noradrenergic network dysfunctions induce attention deficits, including cognitive fluctuation. Abnormality in the cholinergic network is related to visuoperceptual processing dysfunction, which induces visual hallucinations and memory impairments. Pharmacological treatments using cholinesterase inhibitors are effective in improving cognitive function in PD with dementia, which strongly supports the above concept. The pathology of Lewy bodies in the cortical and limbic systems relates to cognitive impairment, and the pathology of cortical amyloids facilitates the progression of cognitive decline in PD. Biomarker studies of cerebrospinal fluid measurements, neuroimaging, and neurophysiology have provided much evidence of cognitive impairment in PD. This review discusses the current knowledge on cognitive impairment in advanced PD, focusing on the distinct neural networks affected by neural degeneration.

Effect of cognitive reserve on cognitive function in Parkinson's disease.

Previous studies showed inconsistent results for the correlation between cognitive reserve (CR) and cognitive function in Parkinson's disease (PD). Additionally, conflicting results were obtained for the association between CR and risk of longitudinal cognitive decline, longitudinal progression to mild cognitive impairment (MCI), and longitudinal progression to dementia in PD patients. Thus, a meta-analysis is essential to summary these inconsistent results. Articles published before November 2021 were searched in databases as follows: PubMed, Web of Science, Medline, EMBASE, and Google Scholar. We computed Fisher's z score and standard error (SE) of each transformation value of correlation coefficient for the correlation between educational level and cognitive function. Additionally, odds ratios (ORs) or hazard ratios (HRs) and their 95% confidence intervals (CIs) were computed as effect sizes for the correlation between educational level and risk of longitudinal progression to MCI. The present study showed that higher educational levels were related to better general cognitive function, executive function, memory, and information processing speed in PD patients, whereas no significant association was showed between educational levels and visuospatial function, language in PD patients. Additionally, included studies reported a negative association between educational level and risk of longitudinal progression to MCI in PD patients. In conclusion, the study demonstrated that higher CR might be correlated with better cognitive function and lower risk of longitudinal progression to MCI in PD. In addition, large-scale prospective studies are necessary to explore the effect of CR on cognitive function in PD.

Effect of eight-week online cognitive training in Parkinson's disease: A double-blind, randomized, controlled trial

IntroductionCognitive training (CT) has been proposed as a treatment option for cognitive impairment in Parkinson's disease (PD). We aimed to assess the efficacy of adaptive, computerized CT on cognitive function in PD. MethodsIn this double-blind, randomized controlled trial we enrolled PD patients that experienced substantial subjective cognitive complaints. Over a period of eight weeks, participants underwent 24 sessions of computerized multi-domain CT or an active control intervention for 45 min each (randomized 1:1). The primary outcome was the accuracy on the Tower of London task; secondary outcomes included effects on other neuropsychological outcomes and subjective cognitive complaints. Outcomes were assessed before and after training and at six-months follow-up, and analyzed with multivariate mixed-model analyses. ResultsThe intention-to-treat population consisted of 136 participants (n = 68 vs. n = 68, age M: 62.9y, female: 39.7%). Multivariate mixed-model analyses showed no group difference on the Tower of London accuracy corrected for baseline performance (n = 130): B: −0.06, 95% CI: −0.27 to 0.15, p = 0.562. Participants in the CT group were on average 0.30 SD (i.e., 1.5 s) faster on difficulty load 4 of this task (secondary outcome): 95% CI: −0.55 to −0.06, p = 0.015. CT did not reduce subjective cognitive complaints. At follow-up, no group differences were found. ConclusionsThis study shows no beneficial effect of eight-week computerized CT on the primary outcome (i.e., planning accuracy) and only minor improvements on secondary outcomes (i.e., processing speed) with limited clinical impact. Personalized or ecologically valid multi-modal intervention methods could be considered to achieve clinically meaningful and lasting effects.

Effects of dance therapy on non-motor symptoms in patients with Parkinson's disease: a systematic review and meta-analysis.

Parkinson's disease (PD) represents the second most common neurodegenerative disease. To evaluate the effects of dance therapy (DT) aimed at improving non-motor symptoms in PD. Studies were performed through PubMed, Web of Science, The Cochrane Library, Embase, and Science Direct from inception to October 27, 2021. The data were screened independently by two reviewers, and the quality of the papers was assessed using the Cochrane manual. The included studies were randomized controlled trials and quasi-randomized controlled trials, reporting random-effects standardized mean differences, and 95% confidence intervals as the effect size. I2 statistics were used to assess heterogeneity. The main outcomes included the Montreal Cognitive Assessment Scale (MOCA), Baker Depression Scale (BDI), Parkinson's Fatigue Scale (FPS-16), and Apathy Scale (AS). RevMan 5.3 software was integrated for meta-analysis. Nine literatures were analyzed for the meta-analysis with a total of 307 patients. Random effects showed that DT significantly improved cognitive of PD (MD = 1.50, 95% CI [0.52, 2.48], P = 0.0003; I2 = 51%). However, this meta-analysis demonstrated that dance therapy had no significance for improving depression (MD = - 1.33, 95% CI [-4.11, 1.45], P = 0.35; I2 = 79%), fatigue (MD = 0.26, 95% CI [-0.31, 0.83], P = 0.37; I2 = 0%), and apathy (MD = 0.07, 95% CI [-2.55, 2.69], P = 0.96; I2 = 50%). The meta-analysis suggests that dance can improve cognitive function in PD.

Cognitive impairment in Parkinson's disease is associated with Default Mode Network subsystem connectivity and cerebrospinal fluid Aβ

IntroductionTo identify clinically implementable biomarkers of cognitive impairment in Parkinson's Disease (PD) derived from resting state-functional MRI (rs-fMRI) and CSF protein analysis. MethodsIn this single-center longitudinal cohort study, we analyzed rs-fMRI and CSF biomarkers from 50 PD patients (23 cognitively normal, 18 mild cognitive impairment, 9 dementia) and 19 controls, who completed comprehensive neuropsychological testing. A subgroup of participants returned for follow-up cognitive assessments three years later. From rs-fMRI, we studied the connectivity within two distinct Default Mode Network subsystems: left-to-right hippocampus (LHC-RHC) and medial prefrontal cortex-to-posterior cingulate cortex (mPFC-PCC). We used regression analyses to determine whether imaging (LHC-RHC, mPFC-PCC), clinical (CSF Aβ-42:40, disease duration), and demographic (age, sex, education) variables were associated with global and domain-specific cognitive impairments. ResultsLHC-RHC (F3,67 = 3.41,p=0.023) and CSF Aβ-42:40 (χ2(3) = 8.77,p = 0.033) were reduced across more cognitively impaired PD groups. Notably, LHC-RHC connectivity was significantly associated with all global and domain-specific cognitive impairments (attention/executive, episodic memory, visuospatial, and language) at the baseline visit. In an exploratory longitudinal analysis, mPFC-PCC was associated with future global and episodic memory impairment. ConclusionWe used biomarker techniques that are readily available in clinical and research facilities to shed light on the pathophysiologic basis of cognitive impairment in PD. Our findings suggest that there is a functionally distinct role of the hippocampal subsystem within the DMN resting state network, and that intrinsic connectivity between the hippocampi is critically related to a broad range of cognitive functions in PD.

Impact of Obstructive Sleep Apnea on Cognitive and Motor Functions in Parkinson's Disease.

Parkinson's disease (PD) is a chronic neurodegenerative disorder that presents with motor and non-motor manifestations. Amongst the non-motor features, various forms of sleep disturbances can occur, and obstructive sleep apnea (OSA) is considered to be a common comorbidity. We conducted this systematic review and meta-analysis to assess the impact of OSA on cognitive and motor functions in PD. The information sources of for this systematic review and meta-analysis were PubMed, SCOPUS, Web of Science, and ScienceDirect. Studies meeting the following criteria were included: (1) studies including idiopathic PD patients, (2) studies using polysomnography to categorize PD patients into PD with OSA and PD without OSA, and (3) studies with observational designs (case-control, cohort, or cross-sectional). Data analysis was performed using RevMan. Our meta-analysis showed that OSA was associated with significantly lower scores of Montreal Cognitive Assessments (MoCA) (mean difference (MD) = -0.70, 95% confidence interval (CI) [-1.28, -0.13], P = 0.01) and Mini-Mental State Examination (MMSE) (MD = -0.69, 95% CI [-1.17, -0.21], P = 0.005). Moreover, the score of the motor part of the Unified Parkinson's Disease Rating Scale (UPDRS III) was significantly higher in PD patients with OSA as compared with those without OSA (MD = 1.63, 95% CI [0.03, 3.23], P = 0.049). OSA is associated with increased severity of PD-associated cognitive dysfunction and motor symptoms. However, further studies are needed to corroborate these findings, assess the underlying mechanisms by which OSA influences the motor and cognitive functions in PD, and investigate whether OSA can accelerate the neurodegenerative process of PD. © 2020 International Parkinson and Movement Disorder Society.

Cholinergic Denervation Patterns Across Cognitive Domains in Parkinson's Disease

The cholinergic system plays a key role in cognitive impairment in Parkinson's disease (PD). Previous acetylcholinesterase positron emission tomography imaging studies found memory, attention, and executive function correlates of global cortical cholinergic losses. Vesicular acetylcholine transporter positron emission tomography allows for more accurate topographic assessment of not only cortical but also subcortical cholinergic changes. The objectiveof this study was to investigate the topographic relationship between cognitive functioning and regional cholinergic innervation in patients with PD. A total of 86 nondemented patients with PD (mean ± SD age 67.8 ± 7.6 years, motor disease duration 5.8 ± 4.6 years), and 12 healthy control participants (age 67.8 ± 7.8 years) underwent cholinergic [18 F]Fluoroethoxybenzovesamicol positron emission tomography imaging. Patients with PD underwent neuropsychological assessment. The z scores for each cognitive domain were determined using an age-matched, gender-matched, and educational level-matched control group. Correlations between domain-specific cognitive functioning and cholinergic innervation were examined, controlling for motor impairments and levodopa equivalent dose. Additional correlational analyses were performed using a mask limited to PD versus normal aging binding differences to assess for disease-specific versus normal aging effects. Voxel-based whole-brain analysis demonstrated partial overlapping topography across cognitive domains, with most robust correlations in the domains of memory, attention, and executive functioning (P < 0.01, corrected for multiple comparisons). The shared pattern included the cingulate cortex, insula/operculum, and (visual) thalamus. Our results confirm and expand on previous observations of cholinergic system involvement in cognitive functioning in PD. The topographic overlap across domains may reflect a partially shared cholinergic functionality underlying cognitive functioning, representing a combination of disease-specific and aging effects. © 2020 International Parkinson and Movement Disorder Society.

Effect of different types of exercises on psychological and cognitive features in people with Parkinson's disease: A randomized controlled trial.

Parkinson's disease (PD) is a neurodegenerative and progressive disease marked by the presence of motor and non-motor symptoms, as psychological and cognitive impairment. Physical exercises have been prescribed as complementary therapy for PD, and the type of intervention and duration of the intervention should be taken into account. We aimed to compare the effect of different exercise modalities (functional mobility, multimodal and cognitive) and length (4 and 8months) on psychological and cognition in people with PD. This study followed the CONSORT extension for non-pharmacological trials. In this randomized controlled trial, we assessed 107participants between 2011 and 2013. At the end of 3years, participants with PD (mild to moderate stages) who achieved the criteria were assessed considering 3 different groups of exercise: Multimodal (n=38), Functional Mobility (n=33) and Mental/Leisure (n=36). All 3 interventions were performed for 32 weeks, twice a week, with 60min for each session (64 sessions in total). Psychological and cognitive function were assessed at baseline and after 4 and 8 months. The Functional Mobility and Mental/Leisure training had a potential effect on maintaining cognitive function (executive function, attention and work memory). The Multimodal training did not show a benefit for cognitive features and was not even able to delay the progressive decline in cognitive functions; however, this modality had a positive effect on physical stress after 8months of exercise. An intervention that requires high complexity and specific activities, such as locomotor and cognitive exercise, provides a maintenance effect against the degeneration in cognition associated with the progression of PD and thus can delay the progressive decline in cognitive function in PD.