Cognitive Impairment In Parkinson's Disease Research Articles

Accuracy of Machine Learning Using the Montreal Cognitive Assessment for the Diagnosis of Cognitive Impairment in Parkinson’s Disease

Objective The Montreal Cognitive Assessment (MoCA) is recommended for assessing general cognition in Parkinson’s disease (PD). Several cutoffs of MoCA scores for diagnosing PD with cognitive impairment (PD-CI) have been proposed, with varying sensitivity and specificity. This study investigated the utility of machine learning algorithms using MoCA cognitive domain scores for improving diagnostic performance for PD-CI.Methods In total, 2,069 MoCA results were obtained from 397 patients with PD enrolled in the Parkinson’s Progression Markers Initiative database with a diagnosis of cognitive status based on comprehensive neuropsychological assessments. Using the same number of MoCA results randomly sampled from patients with PD with normal cognition or PD-CI, discriminant validity was compared between machine learning (logistic regression, support vector machine, or random forest) with domain scores and a cutoff method.Results Based on cognitive status classification using a dataset that permitted sampling of MoCA results from the same individual (n = 221 per group), no difference was observed in accuracy between the cutoff value method (0.74 ± 0.03) and machine learning (0.78 ± 0.03). Using a more stringent dataset that excluded MoCA results (n = 101 per group) from the same patients, the accuracy of the cutoff method (0.66 ± 0.05), but not that of machine learning (0.74 ± 0.07), was significantly reduced. Inclusion of cognitive complaints as an additional variable improved the accuracy of classification using the machine learning method (0.87–0.89).Conclusion Machine learning analysis using MoCA domain scores is a valid method for screening cognitive impairment in PD.

Correlation between serum 25(OH)D and cognitive impairment in Parkinson's disease

This study aimed to investigate the relationship between serum 25(OH)D and cognitive impairment in patients with Parkinson's disease (PD), hoping to provide possible ideas for the diagnosis and prevention of PD with cognitive impairment. Vitamin D is a neurosteroid with neurotrophic and neuroprotective functions, playing an important role in PD and its progression. In the present study, serum 25(OH)D levels were significantly decreased in PD patients (45.86 ± 14.81 nmol/L)compared to healthy controls(56.54 ± 14.00 nmol/L) (P < 0.001), and significant differences were also observed in PD patients with normal cognition (PD-NC), PD patients with mild cognitive impairment (PD-MCI)and PD patients with dementia (PDD)(P < 0.05). Moreover, there was a positive correlation between serum 25(OH)D levels and Montreal cognitive assessment(MoCA) scores (r = 0.489,P < 0.001).The increased serum 25(OH)D was an independent protective factor of cognitive impairment in PD (OR = 0. 949, P = 0.005), and the sensitivity, specificity, and AUC under the ROC curve area of serum 25(OH)D were 53.3%, 86.5%, and 0.713, respectively. These findings support the relationship between cognitive impairment and Vitamin D in PD patients. Serum 25(OH)D may be a useful biomarker for diagnosing cognitive impairment in patients with PD.

Magnetic resonance spectroscopy shows associations between neurometabolite levels and perivascular space volume in Parkinson's disease: a pilot and feasibility study.

Higher volume fraction of perivascular space (PVS) has recently been reported in Parkinson's disease (PD) and related disorders. Both elevated PVS and altered levels of neurometabolites, assayed by proton magnetic resonance spectroscopy (MRS), are suspected indicators of neuroinflammation, but no published reports have concurrently examined PVS and MRS neurometabolites. In an exploratory pilot study, we acquired multivoxel 3-T MRS using a semi-Localization by Adiabatic SElective Refocusing (sLASER) pulse-sequence (repetition time/echo time = 2810/60 ms, voxels 10 × 10 × 10 mm3) from a 2D slab sampling bilateral frontal white matter (FWM) and anterior middle cingulate cortex (aMCC). PVS maps obtained from high-resolution (0.8 × 0.8 × 0.8 mm3) T1-weighted MRI were co-registered with MRS. In each MRS voxel, PVS volume and neurometabolite levels were measured. Linear regression accounting for age, sex, and BMI found greater PVS volume for higher levels of choline-containing compounds (Cho; P = 0.047) in FWM and lower PVS volume for higher levels of N-acetyl compounds (NAA; P = 0.012) in aMCC. Since (putatively) higher Cho is associated with inflammation while NAA has anti-inflammatory properties, these observations add to evidence that higher PVS load is a sign of inflammation. Additionally, lower Montreal Cognitive Assessment scores were associated with lower NAA in aMCC (P = 0.002), suggesting that local neuronal dysfunction and inflammation contribute to cognitive impairment in PD. These exploratory findings indicate that co-analysis of PVS and MRS is feasible and may help elucidate the cellular and metabolic substrates of glymphatic and inflammatory processes 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.

Correspondence between MMSE and detailed neuropsychological testing in Parkinson’s disease

Although the Mini-Mental Status Examination (MMSE) has long been criticised as being insufficiently sensitive to cognitive decline, it is still considered fundamental for the diagnosis of cognitive impairment in Parkinson’s disease, with many papers continuing to use this tool to characterise cognition. This study investigates how intact performance on the MMSE in Parkinson’s disease relates to performance on detailed neuropsychological testing, and how intact performance on individual MMSE subtests corresponds to performance on cognate neuropsychological tests. We examined the wider neuropsychological performance of 264 PD patients screened using the MMSE. 85.7 per cent of PD patients passing the MMSE demonstrated impairment upon detailed neuropsychological assessment, more frequently on non-MMSE domains (76.1 per cent) than MMSE domains (40.8 per cent). Furthermore, despite performing flawlessly on individual MMSE domains, up to 22.6 per cent failed cognate tests upon detailed neuropsychological testing. We conclude that the MMSE is inadequate for the accurate detection or characterisation of cognitive impairment in PD.

Development and Co-design of NeuroOrb: A Novel “Serious Gaming” System Targeting Cognitive Impairment in Parkinson’s Disease

Whilst Parkinson’s disease (PD) is typically thought of as a motor disease, a significant number of individuals also experience cognitive impairment (CI), ranging from mild-CI to dementia. One technique that may prove effective in delaying the onset of CI in PD is cognitive training (CT); however, evidence to date is variable. This may be due to the implementation of CT in this population, with the motor impairments of PD potentially hampering the ability to use standard equipment, such as pen-and-paper or a computer mouse. This may, in turn, promote negative attitudes toward the CT paradigm, which may correlate with poorer outcomes. Consequently, optimizing a system for the delivery of CT in the PD population may improve the accessibility of and engagement with the CT paradigm, subsequently leading to better outcomes. To achieve this, the NeuroOrb Gaming System was designed, coupling a novel accessible controller, specifically developed for use with people with motor impairments, with a “Serious Games” software suite, custom-designed to target the cognitive domains typically affected in PD. The aim of the current study was to evaluate the usability of the NeuroOrb through a reiterative co-design process, in order to optimize the system for future use in clinical trials of CT in individuals with PD. Individuals with PD (n = 13; mean age = 68.15 years; mean disease duration = 8 years) were recruited from the community and participated in three co-design loops. After implementation of key stakeholder feedback to make significant modifications to the system, system usability was improved and participant attitudes toward the NeuroOrb were very positive. Taken together, this provides rationale for moving forward with a future clinical trial investigating the utility of the NeuroOrb as a tool to deliver CT in PD.

Relationship between Plasma Level of Beta-amyloid, Alpha-synuclein, and Tau Protein with Cognitive Impairment in Parkinson Disease

Background: Most people with Parkinson’s disease will develop dementia along with their illness development. There are several overlapping brain pathological features in patients with Parkinson's and Alzheimer's disease. These features are related with beta-amyloid findings, alpha-synuclein and tau protein.&#x0D; Aim: This study was designed to determine the relationship between beta-amyloid, alpha-synuclein and tau protein plasma level with cognitive impairment in Parkinson’s disease. &#x0D; Materials and Methods: This was an observational with case-control design study. Total of 62 patients with Parkinson’s disease and 20 healthy controls were included in this study. Parkinson’s disease group was divided into 2 subgroups, patient with and without cognitive impairment based on Montreal Cognitive Assessment Indonesian version (MoCA-Ina) score. The plasma levels of beta-amyloid, alpha-synuclein, and tau protein were measured by using enzyme-linked immunoassay technique. Student’s t-test was used to analyze normally distributed data of plasma level differences between groups (Parkinson’s disease group; control group) and subgroups (Parkinson disease with and without cognitive impairment). If the data was not normally distributed, we used Mann-Whitney test. The level of significancy was &lt;0.05 (p value &lt;0.05). &#x0D; Results: The result demonstrated significant differences in beta-amyloid, alpha-synuclein, and tau protein plasma level between Parkinson’s disease and control group (p&lt;0.05). We also found significant differences of beta-amyloid plasma level between Parkinson’s with and without cognitive impairment subgroups (p&lt;0.05), but none in other parameters (p&gt;0.05). &#x0D; Conclusion: Low plasma levels of beta-amyloid 42 (Aβ42) are associated with cognitive impairment in patients with Parkinson’s disease.

Paeoniflorin ameliorates cognitive impairment in Parkinson\u2019s disease via JNK/p53 signaling

Paeoniflorin (PF) has numerous benefits, including anti-inflammatory and anti-apoptosis effects. However, it is not clear if it has neuroprotective effects against cognitive impairment (CI) in Parkinson’s disease (PD). Through network pharmacology, we identified probable targets as well as signal pathways through which PF might affect CI in PD. Then, we experimentally validated our findings. The core genes of the protein-protein interactions (PPI) network include MAPK8 (JNK), TP53, CASP3 (caspase-3), postsynaptic density protein-95 (PSD-95) and synaptophysin (SYN). Pathway enrichment analysis revealed that genes involved in apoptosis and mitogen-activated protein kinase (MAPK) signaling were significantly enriched. Because JNK is a key mediator of p53-induced apoptosis, we wondered if JNK/p53 pathway influences the effects of PF against apoptosis in mouse model of PD. Molecular docking analysis showed that PF had good affinity for JNK/p53. The results of the experiments indicated that PF ameliorated behavioral impairments and upregulated the expression of the dopamine (DA) neurons, suppressed cell apoptosis in substantia nigra pars compacta (SNpc) of PD. Additionally, PF improved 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neuronal injury by inhibiting apoptosis in hippocampal neurons of the CA1 and CA3, and upregulating PSD-95 as well as SYN protein levels. Similar protective effects were observed upon JNK/p53 pathway inhibition using SP600125. Overall, PF improved CI in PD by inhibiting JNK/p53 pathway.

Relation of serum level of tumor necrosis factor-alpha to cognitive functions in patients with Parkinson\u2019s disease

BackgroundInflammation is suggested to play a role in the development of non-motor Parkinson’s disease (PD) symptoms. We aimed to investigate the association between serum tumor necrosis factor-alpha (TNF-α) levels and cognition in PD patients. Thirty patients with PD and 30 healthy controls were included. Evaluation and staging of PD were done using Unified PD Rating Scale. Cognitive assessment was done using Addenbrooke’s Cognitive Examination (ACE-III) and trail making B tests. Measurement of serum levels of TNF-α was done.ResultsPatients had significantly worser cognitive scores than controls except for language subclass of ACE score. Mean serum TNF-α level was significantly greater in PD patients as compared to controls. TNF-α serum level was significantly negatively correlated with ACE visuospatial function. Sensitivity and specificity of TNF-α to detect cognitive dysfunction in PD using ACE III and trail making B tests were (73.1, 75%), (57.1, 56.2%), respectively, whereas sensitivity and specificity of TNF-α to detect severity of PD using H&Y staging in PD were 50%.ConclusionPatients with PD frequently have cognitive impairment. Elevated serum TNF-α levels in patients with PD, and association of this cytokine to visuospatial impairment, implicate this pro-inflammatory cytokine in the neurobiology of cognitive impairment in PD.

Ambroxol reverses tau and α-synuclein accumulation in a cholinergic N370S GBA1 mutation model.

Cognitive impairment is a common non-motor complication of Parkinson’s disease (PD). Glucocerebrosidase gene (GBA1) variants are found in 10–15% of PD cases and are numerically the most important risk factor for PD and dementia with Lewy bodies. Accumulation of α-synuclein and tau pathology is thought to underlie cognitive impairment in PD and likely involves cholinergic as well as dopaminergic neurons. Neural crest stem cells were isolated from both PD patients with the common heterozygous N370S GBA1 mutation and normal subjects without GBA1 mutations. The stem cells were used to generate a cholinergic neuronal cell model. The effects of the GBA1 variant on glucocerebrosidase (GCase) protein and activity, and cathepsin D, tau and α-synuclein protein levels in cholinergic neurons were examined. Ambroxol, a GCase chaperone, was used to investigate whether GCase enhancement was able to reverse the effects of the GBA1 variant on cholinergic neurons. Significant reductions in GCase protein and activity, as well as in cathepsin D levels, were found in GBA1 mutant (N370S/WT) cholinergic neurons. Both tau and α-synuclein levels were significantly increased in GBA1 mutant (N370S/WT) cholinergic neurons. Ambroxol significantly enhanced GCase activity and decreased both tau and α-synuclein levels in cholinergic neurons. GBA1 mutations interfere with the metabolism of α-synuclein and tau proteins and induce higher levels of α-synuclein and tau proteins in cholinergic neurons. The GCase pathway provides a potential therapeutic target for neurodegenerative disorders related to pathological α-synuclein or tau accumulation.

Magnetic Resonance Imaging Markers for Cognitive Impairment in Parkinson's Disease: Current View.

Cognitive impairment (CI) ranging from mild cognitive impairment (MCI) to dementia is a common and disturbing complication in patients with Parkinson’s disease (PD). Numerous studies have focused on neuropathological mechanisms underlying CI in PD, along with the identification of specific biomarkers for CI. Magnetic resonance imaging (MRI), a promising method, has been adopted to examine the changes in the brain and identify the candidate biomarkers associated with CI. In this review, we have summarized the potential biomarkers for CI in PD which have been identified through multi-modal MRI studies. Structural MRI technology is widely used in biomarker research. Specific patterns of gray matter atrophy are promising predictors of the evolution of CI in patients with PD. Moreover, other MRI techniques, such as MRI related to small-vessel disease, neuromelanin-sensitive MRI, quantitative susceptibility mapping, MR diffusion imaging, MRI related to cerebrovascular abnormality, resting-state functional MRI, and proton magnetic resonance spectroscopy, can provide imaging features with a good degree of prediction for CI. In the future, novel combined biomarkers should be developed using the recognized analysis tools and predictive algorithms in both cross-sectional and longitudinal studies.

Altered Cholinergic Innervation in De Novo Parkinson's Disease with and Without Cognitive Impairment.

BackgroundAltered cholinergic innervation plays a putative role in cognitive impairment in Parkinson's disease (PD) at least in advanced stages. Identification of the relationship between cognitive impairment and cholinergic innervation early in the disease will provide better insight into disease prognosis and possible early intervention.ObjectiveThe aim was to assess regional cholinergic innervation status in de novo patients with PD, with and without cognitive impairment.MethodsFifty‐seven newly diagnosed, treatment‐naive, PD patients (32 men, mean age 64.6 ± 8.2 years) and 10 healthy controls (5 men, mean age 54.6 ± 6.0 years) were included. All participants underwent cholinergic [18F]fluoroethoxybenzovesamicol positron emission tomography and detailed neuropsychological assessment. PD patients were classified as either cognitively normal (PD‐NC) or mild cognitive impairment (PD‐MCI). Whole brain voxel‐based group comparisons were performed.ResultsResults show bidirectional cholinergic innervation changes in PD. Both PD‐NC and PD‐MCI groups showed significant cortical cholinergic denervation compared to controls (P < 0.05, false discovery rate corrected), primarily in the posterior cortical regions. Higher‐than‐normal binding was most prominent in PD‐NC in both cortical and subcortical regions, including the cerebellum, cingulate cortex, putamen, gyrus rectus, hippocampus, and amygdala.ConclusionAltered cholinergic innervation is already present in de novo patients with PD. Posterior cortical cholinergic losses were present in all patients independent of cognitive status. Higher‐than‐normal binding in cerebellar, frontal, and subcortical regions in cognitively intact patients may reflect compensatory cholinergic upregulation in early‐stage PD. Limited or failing cholinergic upregulation may play an important role in early, clinically evident cognitive impairment in PD. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Analysis of Brain Activity Changes in Patients with Parkinson's Disease Based on Resting-State Functional Magnetic Resonance Imaging.

This paper uses resting-state functional magnetic resonance imaging to observe the changes in local consistency of brain activity in patients with Parkinson's disease (PD). Both healthy volunteers and Parkinson's disease patients were scanned for resting brain functional imaging, and the collected raw data were processed using resting functional magnetic resonance data processing toolkit software. This study adopted the use of Regional Homogeneity (ReHo). The postprocessing method of RS-fMRI is to study the spontaneous brain activity changes of patients with Parkinson's disease and cognitive impairment and to explore the changes in the function of their brain regions in the hope of providing help for the treatment of Parkinson's disease cognitive impairment. The results showed that, compared with the normal control group, the brain regions with increased ReHo values in the PD group were the right central anterior gyrus, the right lingual gyrus, the left middle occipital gyrus, and the bilateral anterior cuneiform lobes. The results show that PD patients have abnormal brain nerve activities in the resting state, and these abnormal brain nerve activities may be related to PD cognitive and behavioral dysfunction.

Hydrogen Sulfide Attenuates the Cognitive Dysfunction in Parkinson's Disease Rats via Promoting Hippocampal Microglia M2 Polarization by Enhancement of Hippocampal Warburg Effect.

Identification of innovative therapeutic targets for the treatment of cognitive impairment in Parkinson's disease (PD) is urgently needed. Hydrogen sulfide (H2S) plays an important role in cognitive function. Therefore, this work is aimed at investigating whether H2S attenuates the cognitive impairment in PD and the underlying mechanisms. In the rotenone- (ROT-) established PD rat model, NaHS (a donor of H2S) attenuated the cognitive impairment and promoted microglia polarization from M1 towards M2 in the hippocampus of PD rats. NaHS also dramatically upregulated the Warburg effect in the hippocampus of PD rats. 2-Deoxyglucose (2-DG, an inhibitor of the Warburg effect) abolished NaHS-upregulated Warburg effect in the hippocampus of PD rats. Moreover, the inhibited hippocampal Warburg effect by 2-DG abrogated H2S-excited the enhancement of hippocampal microglia M2 polarization and the improvement of cognitive function in ROT-exposed rats. Our data demonstrated that H2S inhibits the cognitive dysfunction in PD via promoting microglia M2 polarization by enhancement of hippocampal Warburg effect.

Quantitative Electroencephalography as a Biomarker for Cognitive Dysfunction in Parkinson's Disease.

Background: Quantitative electroencephalography (qEEG) has been suggested as a biomarker for cognitive decline in Parkinson’s disease (PD).Objective: Determine if applying a wavelet-based qEEG algorithm to 21-electrode, resting-state EEG recordings obtained in a routine clinical setting has utility for predicting cognitive impairment in PD.Methods: PD subjects, evaluated by disease stage and motor score, were compared to healthy controls (N = 20 each). PD subjects with normal (PDN, MoCA 26–30, N = 6) and impaired (PDD, MoCA ≤ 25, N = 14) cognition were compared. The wavelet-transform based time-frequency algorithm assessed the instantaneous predominant frequency (IPF) at 60 ms intervals throughout entire recordings. We then determined the relative time spent by the IPF in the four standard EEG frequency bands (RTF) at each scalp location. The resting occipital rhythm (ROR) was assessed using standard power spectral analysis.Results: Comparing PD subjects to healthy controls, mean values are decreased for ROR and RTF-Beta, greater for RTF-Theta and similar for RTF-Delta and RTF-Alpha. In logistic regression models, arithmetic combinations of RTF values [e.g., (RTF-Alpha) + (RTF-Beta)/(RTF-Delta + RTF-Theta)] and RTF-Alpha values at occipital or parietal locations are most able to discriminate between PD and controls. A principal component (PC) from principal component analysis (PCA) using RTF-band values in all subjects is associated with PD status (p = 0.004, β = 0.31, AUC = 0.780). Its loadings show positive contribution from RTF-Theta at all scalp locations, and negative contributions from RTF-Beta at occipital, parietal, central, and temporal locations. Compared to cognitively normal PD subjects, cognitively impaired PD subjects have lower median RTF-Alpha and RTF-Beta values, greater RTF-Theta values and similar RTF-Delta values. A PC from PCA using RTF-band values in PD subjects is associated with cognitive status (p = 0.002, β = 0.922, AUC = 0.89). Its loadings show positive contributions from RTF-Theta at all scalp locations, negative contributions from RTF-Beta at central locations, and negative contributions from RTF-Delta at central, frontal and temporal locations. Age, disease duration and/or sex are not significant covariates. No PC was associated with motor score or disease stage.Significance: Analyzing standard EEG recordings obtained in a community practice setting using a wavelet-based qEEG algorithm shows promise as a PD biomarker and for predicting cognitive impairment in PD.

Cognition and serotonin in Parkinson's disease.

Cognitive impairment affects up to 80% of patients with Parkinson's disease (PD) and is associated with poor quality of life. PD cognitive dysfunction includes poor working memory, impairments in executive function and difficulty in set-shifting. The pathophysiology underlying cognitive impairment in PD is still poorly understood, but there is evidence to support involvements of the cholinergic, dopaminergic, and noradrenergic systems. Only rivastigmine, an acetyl- and butyrylcholinesterase inhibitor, is efficacious for the treatment of PD dementia, which limits management of cognitive impairment in PD. Whereas the role of the serotonergic system in PD cognition is less understood, through its interactions with other neurotransmitters systems, namely, the cholinergic system, it may be implicated in cognitive processes. In this chapter, we provide an overview of the pharmacological, clinical and pathological evidence that implicates the serotonergic system in mediating cognition in PD.

Management of Psychiatric Disorders in Patients with Parkinson's Diseases.

Parkinson’s disease (PD) is a heterogeneous progressive neurodegenerative disorder, with a triad of motor symptoms with akinesia/bradykinesia, resting tremor (4–6 Hz), and rigidity. It is the second most common neurodegenerative disease after Alzheimer’s disease. The overall management of PD depends on the status of symptoms, functioning of the patients, impairment, disability, and its impact on quality of life. Depression, anxiety disorders, apathy, anhedonia, psychosis, cognitive impairments, dementia, and impulse control disorders (ICDs) are the common psychiatric symptoms/disorders comorbid with PD. Depression remains the most common psychiatric disorder reported to be comorbid with PD. Several pharmacological and nonpharmacological management strategies are used for the treatment of comorbid psychiatric disorders in PD. Selective serotonin reuptake inhibitors and serotonin norepinephrine reuptake inhibitors are used to treat depression in patients with PD. The best evidence of efficacy in PD psychosis is for clozapine and pimavanserin. The treatment for cognitive impairments in PD remains poorly researched. Rivastigmine is the only approved treatment for PD as per the Food and Drug Administration. Pramipexole, a dopamine agonist (DA), is reported to cause improvement in the symptoms of decreased willingness in apathy. The treatment approaches for different sleep disorders in PD are different. Identifying the cause, reviewing the patient’s ongoing medications, and evaluating the impact of comorbid medical conditions and sleep hygiene are common to all conditions related to sleep disorders. The first approach for treating ICD symptoms is the reduction or discontinuation of DAs. The psychiatric symptoms in patients with PD are highly prevalent, and their management should be included in the basic treatment algorithm for PD. This paper summarizes common psychiatric symptoms/disorders in PD and their management approaches.

Real-life consequences of cognitive dysfunction in Parkinson's disease.

While motor symptoms are the most recognized features of Parkinson's disease (PD), cognitive dysfunction is a key determinant of consequences of PD in real-life. In this chapter we review important domains where cognitive dysfunction negatively impacts the lives of people with PD (PwPD), such as difficulties in occupational and social life, and instrumental ADLs such as driving. Early loss of employment has important effects for PwPD, their families, and society. PwPD experience higher rates of family and social discord as well as important changes in their social roles. These processes are largely mediated through cognitive dysfunction, particularly difficulties processing and understanding emotions, decreased attention, and executive dysfunction. Cognitive dysfunction is also an important mediator of driving impairments, which contributes to decreased independence in PwPD. Finally, we briefly review the costs associated with cognitive impairment in PD. Both indirect and direct costs for PwPD with cognitive impairment are substantially higher than for PwPD with normal cognition.

Alterations in Large-Scale Intrinsic Connectivity Networks in the Parkinson's Disease-Associated Cognitive Impairment Continuum: A Systematic Review.

Cognitive impairment is common in the course of Parkinson's disease (PD) and displays a continuum from subjective cognitive impairment to dementia. Illuminating the pathophysiological processes associated with the continuum may help create follow-up and new treatment approaches. In this context, large-scale intrinsic connectivity networks are widely investigated to elucidate the neural processes underlying PD and are promising as non-invasive biomarkers. This systematic review aims to examine the alterations in large-scale intrinsic connectivity networks in the continuum of PD-associated cognitive impairment. ScienceDirect, Web of Science, and PubMed databases were searched with the specified keywords. The studies obtained as a result of this review were investigated by the PRISMA criteria, which were taken as a basis for the systematic review and writing of meta-analyses. A total of 974 studies were obtained from three databases. Twenty studies were included in the systematic review based on predetermined eligibility criteria. Among the large-scale connectivity networks examined in these studies, it was found that sensory-motor networks decreased their connectivity in the continuum of PD-associated cognitive impairment, and there were conflicting results in terms of cognitive networks. Well-designed longitudinal studies are needed to clarify the alterations in the intrinsic connectivity networks in the PD cognitive impairment continuum. In these studies, it is necessary to define the cognitive disorder groups well, to control the connectivity changes that may occur due to dopaminergic treatment, and to evaluate Parkinson's patients with subjective cognitive impairment and dementia within the continuum.

Mapping Actuarial Criteria for Parkinson's Disease-Mild Cognitive Impairment onto Data-Driven Cognitive Phenotypes.

Prevalence rates for mild cognitive impairment in Parkinson’s disease (PD-MCI) remain variable, obscuring the diagnosis’ predictive utility of greater dementia risk. A primary factor of this variability is inconsistent operationalization of normative cutoffs for cognitive impairment. We aimed to determine which cutoff was optimal for classifying individuals as PD-MCI by comparing classifications against data-driven PD cognitive phenotypes. Participants with idiopathic PD (n = 494; mean age 64.7 ± 9) completed comprehensive neuropsychological testing. Cluster analyses (K-means, Hierarchical) identified cognitive phenotypes using domain-specific composites. PD-MCI criteria were assessed using separate cutoffs (−1, −1.5, −2 SD) on ≥2 tests in a domain. Cutoffs were compared using PD-MCI prevalence rates, MCI subtype frequencies (single/multi-domain, executive function (EF)/non-EF impairment), and validity against the cluster-derived cognitive phenotypes (using chi-square tests/binary logistic regressions). Cluster analyses resulted in similar three-cluster solutions: Cognitively Average (n = 154), Low EF (n = 227), and Prominent EF/Memory Impairment (n = 113). The −1.5 SD cutoff produced the best model of cluster membership (PD-MCI classification accuracy = 87.9%) and resulted in the best alignment between PD-MCI classification and the empirical cognitive profile containing impairments associated with greater dementia risk. Similar to previous Alzheimer’s work, these findings highlight the utility of comparing empirical and actuarial approaches to establish concurrent validity of cognitive impairment in PD.