PD Patients With Mild Cognitive Impairment Research Articles

Parkinson's disease CA2-CA3 hippocampal atrophy is accompanied by increased cholinergic innervation in patients with normal cognition but not in patients with mild cognitive impairment.

Although brain cholinergic denervation has been largely associated with cognitive decline in patients with Parkinson's disease (PD), new evidence suggests that cholinergic upregulation occurs in the hippocampus of PD patients without cognitive deficits. The specific hippocampal sectors and potential mechanisms of this cholinergic compensatory process have been further studied here, using MRI volumetry and morphometry coupled with molecular imaging using the PET radiotracer [18F]-Fluoroethoxybenzovesamicol ([18F]-FEOBV). Following a thorough screening procedure, 18 participants were selected and evenly distributed in three groups, including cognitively normal PD patients (PD-CN), PD patients with mild cognitive impairment (PD-MCI), and healthy volunteers (HV). Participants underwent a detailed neuropsychological assessment, structural MRI, and PET imaging with [18F]-FEOBV. Basal forebrain Ch1-Ch2 volumes were measured using stereotaxic mapping. Hippocampal subfields were automatically defined using the MAGeT-Brain segmentation algorithm. Cholinergic innervation density was quantified using [18F]-FEOBV uptake. Compared with HV, both PD-CN and PD-MCI displayed significantly reduced volumes in CA2-CA3 bilaterally. We found no other hippocampal subfield nor Ch1-Ch2 volume differences between the three groups. PET imaging revealed higher [18F]-FEOBV uptake in CA2-CA3 of the PD-CN compared with HV or PD-MCI. A positive correlation was observed between cognitive performances and [18F]-FEOBV uptake in the right CA2-CA3 subfield. Reduced volume, together with increased [18F]-FEOBV uptake, were observed specifically in the CA2-CA3 hippocampal subfields. However, while the volume change was observed in both PD-CN and PD-MCI, increased [18F]-FEOBV uptake was present only in the PD-CN group. This suggests that a cholinergic compensatory process takes place in the atrophied CA2-CA3 hippocampal subfields and might underlie normal cognition in PD.

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.

Proteomic comparison between non-purified cerebrospinal fluid and cerebrospinal fluid-derived extracellular vesicles from patients with Alzheimer's, Parkinson's and Lewy body dementia.

Dementia is a leading cause of death worldwide, with increasing prevalence as global life expectancy increases. The most common neurodegenerative disorders are Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD). With this study, we took an in-depth look at the proteome of the (non-purified) cerebrospinal fluid (CSF) and the CSF-derived extracellular vesicles (EVs) of AD, PD, PD-MCI (Parkinson's disease with mild cognitive impairment), PDD and DLB patients analysed by label-free mass spectrometry. This has led to the discovery of differentially expressed proteins that may be helpful for differential diagnosis. We observed a greater number of differentially expressed proteins in CSF-derived EV samples (N=276) compared to non-purified CSF (N=169), with minimal overlap between both datasets. This finding suggests that CSF-derived EV samples may be more suitable for the discovery phase of a biomarker study, due to the removal of more abundant proteins, resulting in a narrower dynamic range. As disease-specific markers, we selected a total of 39 biomarker candidates identified in non-purified CSF, and 37 biomarker candidates across the different diseases under investigation in the CSF-derived EV data. After further exploration and validation of these proteins, they can be used to further differentiate between the included dementias and may offer new avenues for research into more disease-specific pharmacological therapeutics.

Associations of blood UCH-L1 and NfL levels with cognitive dysfunction in Parkinson’s disease patients

ObjectiveUbiquitin carboxy-terminal hydrolase L1 (UCH-L1) and Neurofilament light chain (NfL) are associated with Lewy body formation, Lewy bodies are the main pathological feature of Parkinson's disease (PD). The relationship between UCH-L1 and PD cognition remains unclear, and NfL is an important marker of cognitive impairment. The aim of this study is to investigate the relationship among serum UCH-L1 levels, plasma NfL levels and cognitive dysfunction in PD patients. ResultsThere were significant differences in UCH-L1 and NfL levels among PD patients with normal cognitive function (PD-CN), PD patients with mild cognitive impairment (PD-MCI), and PD-dementia patients (PDD) (P < 0.001; P < 0.001). The PDD group had lower levels of UCH-L1 (Z = 6.721, P < 0.001; Z = 7.577, P < 0.001) and higher levels of NfL (Z = −3.626, P = 0.001; Z = −2.616P = 0.027) than the PD-NC and PD-MCI groups. Serum UCH-L1 levels were positively correlated with MMSE scores, MoCA scores, and its subitems in PD patients (P < 0.001), and plasma NfL levels were negatively correlated with MMSE scores, MoCA scores, and its items (P < 0.01) (except for “abstract”). ConclusionDecreased UCH-L1 levels and elevated NfL levels in the blood are associated with cognitive dysfunction in PD; thus, these proteins are potential biomarkers for the diagnosis of cognitive dysfunction in PD patients.

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.

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.

Neural correlates of working memory and compensation at different stages of cognitive impairment in Parkinson’s disease

Working memory (WM) impairment is one of the most frequent cognitive deficits in Parkinson's disease (PD). However, it is not known how neural activity is altered and compensatory responses eventually fail during progression. We aimed to elucidate neural correlates of WM and compensatory mechanisms in PD. Eighteen cognitively normal PD patients (PD-CogNL), 16 with PD with mild cognitive impairment (PD-MCI), 11 with PD with dementia (PDD), and 17 healthy controls (HCs) were evaluated. Subjects performed an n-back task. Functional MRI data were analyzed by event-related analysis for correct responses. Brain activations were evaluated by comparing them to fixation cross or 0-back task, and correlated with n-back task performance. When compared to fixation cross, PD-CogNL patients had more activation in WM areas than HCs for both the 2- and 3-back tasks. PD-MCI and PDD patients had more activation in WM areas than HCs for the 0- and 1-back task. 2-back task performance was correlated with brain activations (vs. 0-back task) in the bilateral dorsolateral prefrontal cortex and frontal eye field (FEF) and left rostral prefrontal cortex, caudate nucleus, inferior/superior parietal lobule (IPL/SPL), and anterior insular cortex as well as anterior cingulate cortex. 3-back task performance was correlated with brain activations (vs. 0-back task) in the left FEF, right caudate nucleus, and bilateral IPL/SPL. Additional activations on top of the 0-back task, rather than fixation cross, are the neural correlates of WM. Our results suggest PD patients have two types of compensatory mechanisms: (1) Hyperactivation for different WM load tasks depending on their cognitive status. PD-CogNL have hyperactivation for moderate and heavy working memory load tasks while maintaining normal working memory performance. In contrast, PD-MCI and PDD have hyperactivation for control task and light working memory load task, leaving less neural resources to further activate for more demanding tasks and resulting in impaired working memory performance. (2) Bilateral recruitment of WM-related areas, in particular the DLPFC, FEF, IPL/SPL and caudate nucleus, to improve WM performance.

Cerebrospinal fluid A/T/(N) profile and mild cognitive impairment in Parkinson's disease

In synucleinopathies, the presence of an underlying Alzheimer's disease (AD) pathology can be involved in cognitive decline. Cerebrospinal fluid (CSF) profile consistent with amyloidosis, as well as CSF AD signature are sometimes reported in Parkinson's disease (PD) with dementia. Additionally, decreased CSF Aβ42 levels predict earlier appearance of cognitive decline in PD. However, contradictory results are available for CSF AD biomarkers in PD patients with mild cognitive impairment (PD-MCI). Our aim was to assess potential correlation between CSF AD biomarkers and PD-MCI.

The influence of white matter hyperintensity on cognitive impairment in Parkinson's disease.

The aim of this meta‐analysis was to review systematically and to identify the relationship between the severity and location of white matter hyperintensities (WMHs) and the degree of cognitive decline in patients with Parkinson’s disease (PD). We searched the PubMed, EMBASE, Web of Science, Ovid, and Cochrane Library databases for clinical trials of the severity and location of WMHs on the degree of cognitive impairment in PD through October 2020. We conducted the survey to compare the association of WMH burden in patients with PD with mild cognitive impairment (PD‐MCI) versus those with normal cognition (PD‐NC) and in patients with PD with dementia (PDD) versus those with PD without dementia (PD‐ND). Nine studies with PD‐MCI versus PD‐NC and 10 studies with PDD versus PD‐ND comparisons were included. The WMH burden in PD‐MCI patients was significantly different compared to that in PD‐NC patients (standard mean difference, SMD = 0.39, 95% CI: 0.12 to 0.66, p = 0.005), while there was no correlation shown in the age‐matched subgroup of the comparison. In addition, PDD patients had a significantly higher burden of WMHs (SMD = 0.8, 95% CI: 0.44 to 1.71, p < 0.0001), especially deep white matter hyperintensities (SMD = 0.54, 95% CI: 0.36 to 0.73, p < 0.00001) and periventricular hyperintensities (SMD = 0.70, 95% CI: 0.36 to 1.04, p < 0.0001), than PD‐NC patients, regardless of the adjustment of age. WMHs might be imaging markers for cognitive impairment in PDD but not in PD‐MCI, regardless of age, vascular risk factors, or race. Further prospective studies are needed to validate the conclusions.

Evaluation of the efficacy of physical therapy on cognitive decline at 6-month follow-up in Parkinson disease patients with mild cognitive impairment: a randomized controlled trial.

In Parkinson's disease (PD), physical activity may represent a possible non-pharmacological intervention not only for improving motor symptoms but also for modulating cognitive impairment. To evaluate the efficacy of an intensive physical program on cognitive functions in mid-stage PD patients with mild cognitive impairment (PD-MCI) over a 6-month follow-up. This is a 6-month randomized controlled follow-up study. 40 PD-MCI patients were randomized to receive physical therapy (PT) or no specific intervention beside drug treatment (CT). Cognitive and motor assessments were performed at baseline (T0), 4weeks after baseline (T1) and 6months after T0. In a previous study, we reported a significant improvement in global cognitive functioning and attention/working-memory at T1. Here, we evaluated the residual effect of the training intervention at 6months on both cognitive and motor performances. Intra-group analysis showed that at T2 most of cognitive and motor performances remained stable in the PT when compared to T0, while a significant worsening was observed in the CT. Between-group comparison at T2 showed significantly better results in PT than CT as regards MoCA and motor scales. The percentage change of cognitive and motor performances between T1 and T2 confirmed the benefit of physical therapy on global cognitive functioning scores (MMSE and MoCA). In this follow-up extension of a longitudinal randomized controlled study, we demonstrated that physical therapy has a positive effect on cognitive functions, which extends beyond the duration of the treatment itself to, at least temporarily, reducing cognitive decline. Trial registration number (ClinicalTrials.gov): NCT04012086 (9th July 2019).

Aberrant voxel-based degree centrality in Parkinson’s disease patients with mild cognitive impairment

The purpose was to explore the intrinsic dysconnectivity pattern of whole-brain functional networks in Parkinson's disease patients with mild cognitive impairment (PD-MCI) using a voxel-wise degree centrality (DC) analysis approach. The resting-state functional magnetic resonance imaging (rs-fMRI) scanning was performed in all subjects including PD-MCI, PD patients with no cognitive impairment (PD-NCI), and healthy controls (HCs). DC mapping was used to identify functional connectivity (FC) alterations among these groups. Correlation between abnormal DC and clinical features was performed. Secondary seed-based FC analyses and voxel-based morphometry (VBM) analyses were also conducted. Compared with HCs, PD-MCI and PD-NCI showed DC abnormalities mainly in the right temporal lobe, thalamus, left cuneus, middle frontal gyrus, and corpus callosum. Compared with PD-NCI, PD-MCI showed abnormal DC in the left fusiform gyrus (FFG) and left cerebellum lobule VI, left cuneus, right hippocampus, and bilateral precuneus. In PD-MCI patients, correlation analyses revealed that DC in the left FFG was positively correlated with the Montreal Cognitive Assessment (MoCA) scores, and DC in the left precuneus was negatively correlated with the MoCA scores. Secondary seed-based FC analysis further revealed FC changes mainly in the default mode network, right middle cingulum, right supramarginal gyrus, and right postcentral/precentral gyrus. However, no significant difference was found in the secondary VBM analysis. The findings suggest that dysfunction in extensive brain areas is involved in PD-MCI. Among these regions, the left precuneus, FFG, and cerebellum VI may be the key hubs in the pathogenesis of PD-MCI.

Mild cognitive impairment in patients with Parkinson's disease and the analysis of associated factors

Objective: The purpose of this study is to investigate the relationship between cognition and motor symptoms, nonmotor symptoms, white matter hyperintensities(WMHs) and biochemical parameters in Parkinson's disease patients with mild cognitive impairment (PD-MCI).

Assessment of White Matter Lesions in Parkinson's Disease: Voxel-based Analysis and Tract-based Spatial Statistics Analysis of Parkinson's Disease with Mild Cognitive Impairment.

Application of diffusion tensor imaging (DTI) to explore the changes of FA value in patients with Parkinson's disease (PD) with mild cognitive impairment. 27 patients with PD were divided into PD with mild cognitive impairment (PD-MCI) group (n = 7) and PD group (n = 20). The original images were processed using voxel-based analysis (VBA) and tract-based spatial statistics (TBSS). The average age of pd-mci group was longer than that of PD group, and the course of disease was longer than that of PD group. Compared with PD group, the voxel based analysis-fractional anisotropy (VBA-FA) values of PD-MCI group decreased in the following areas: bilateral frontal lobe, bilateral temporal lobe, bilateral parietal lobe, bilateral subthalamic nucleus, corpus callosum, and gyrus cingula. Tract-based spatial statistics-fractional anisotropy (TBSS-FA) values in PD-MCI group decreased in bilateral corticospinal tract, anterior cingulum, posterior cingulum, fornix tract, bilateral superior thalamic radiation, corpus callosum(genu, body and splenium), bilateral uncinate fasciculus, bilateral inferior longitudinal fasciculus, bilateral superior longitudinal fasciculus, bilateral superior fronto-occipital fasciculus, bilateral inferior fronto-occipital fasciculus, and bilateral parietal-occipital tracts. The mean age of onset in the PD-MCI group was greater than that in the PD group, and the disease course was longer than that in the PD group. DTI-based VBA and TBSS post-processing methods can detect abnormalities in multiple brain areas and white matter fiber tracts in PD-MCI patients. Impairment of multiple cerebral cortex and white matter fiber pathways may be an important causes of cognitive dysfunction in PD-MCI.

Determinants of Quality of Life According to Cognitive Status in Parkinson's Disease.

BackgroundQuality of life (QoL) was worse in Parkinson’s disease patients with mild cognitive impairment (PD-MCI) or dementia (PDD) than PD patients with normal cognition (PD-NC). The aim of this study was to investigate and compare the potential heterogeneous determinants of QoL in PD patients with different cognitive statuses.MethodsWe recruited 600 PD patients, including 185 PD-NC patients, 336 PD-MCI patients and 79 PDD patients, in this cross-sectional study. All patients completed the QoL assessment by the 39-item Parkinson’s Disease Questionnaire (PDQ-39), as well as clinical evaluations and neuropsychological tests. The determinants of the QoL were analyzed by multiple stepwise regression analysis.ResultsQoL was more impaired across the three groups (PD-NC < PD-MCI < PDD). The Unified Parkinson’s Disease Rating Scale part III (UPDRS-III) score, Geriatric Depression Rating Scale (GDS) score and daily levodopa equivalent dose (LED) were independent variables of PDQ-39 in PD-NC patients. The GDS score, disease duration, UPDRS-III score, Epworth Sleepiness Score (ESS) and sex were independent variables of PDQ-39 in PD-MCI patients. The GDS score and disease duration were independent variables of PDQ-39 in PDD patients.ConclusionThe determinants of QoL in PD-NC, PD-MCI and PDD patients were heterogeneous. Motor function was considered to be the most crucial determinant for QoL in PD-NC, while depression was indicated to be the most vital determinant for PD-MCI and PDD. For QoL improvement, clinicians might need to focus more on motor function in PD-NC patients and on depression in PD-MCI and PDD patients.

Cognitive Function and Quality of Life inParkinson's Disease: A Cross-Sectional Study.

Parkinson's disease with mild cognitive impairment (PD-MCI) or dementia (PDD) has been shown to be correlated with poor quality of life (QoL). The association between specific cognitive domains and QoL is less clear. To determine how the cognitive domains affect QoL in different cognitive states in PD. We recruited 600 PD patients, including 185 PD patients with normal cognition (PD-NC), 336 PD-MCI patients, and 79 PDD patients. All patients underwent a scale-based assessment (PDQ-39) for QoL, as well as clinical evaluations and neuropsychological tests. Compared to PD-NC group, QoL became more impaired in the PD-MCI and PDD groups. Generalized linear model revealed that no neuropsychological test was significantly associated with QoL in PD-NC group; neuropsychological tests in attention and language domains were significantly associated with QoL in PD-MCI patients; neuropsychological tests in memory and language domains were significantly associated with QoL in PDD patients. Cognitive domains contribute differently to QoL in PD. These findings may prompt clinicians to target specific cognitive domains for improving QoL in the PD patients.

Association of the serum microRNA-29 family with cognitive impairment in Parkinson's disease.

We aimed to examine whether miRNA-29s (miR-29s) in serum are associated with cognitive impairment in Parkinson’s disease (PD). Thirty-nine PD patients with normal cognition (PD-NC), 37 PD patients with mild cognitive impairment (PD-MCI), 22 PD patients with dementia (PDD) and 40 healthy controls were recruited. Detailed clinical evaluations and a schedule of neuropsychological tests were administered to all patients. MiR-29s expression in serum samples was assessed using reverse-transcription quantitative real-time PCR. We found that the levels of all three miR-29s in the PDD group were significantly lower than those in the PD-NC group (p < 0.05). In addition, the miR-29b level was downregulated in the PD-MCI group with respect to that in the PD-NC group (p < 0.05). After adjusting for years of education and the UPDRS-III subscore using a multivariate model, miR-29s showed significant associations with PDD. MiR-29b levels were shown to be associated with different subsets of PD cognition and could accurately discriminate PDD from non-PDD (area under the curve (AUC) = 0.859; 95% CI, 0.7817-0.9372). Further analysis of the cognitive domains found that the miR-29s levels were all associated with memory performance in PD patients. In summary, miR-29s are associated with cognitive impairment in PD.

Association of cognitive activities of daily living (ADL) function and nonmotor burden in nondemented Parkinson's disease patients.

In Parkinson's disease (PD), nonmotor symptoms (NMS) considerably influence disease progression and cognitive decline. Depression, anxiety, sleep disturbances, and hallucinations (DASH), may indicate a risk for dementia (PDD). Mild impairments in activities of daily living (ADL) caused by cognitive dysfunction are also present in the prodromal stage of PDD. The association of both factors has been sparsely investigated. Aim was to evaluate these specific NMS in a large nondemented PD cohort and their co-occurrence with cognitive dysfunction and ADL impairments. Data of 226 PD patients was analyzed. Using corresponding items, two DASH scores were constructed from the NMS-Scale and Parkinson's disease Questionnaire (PDQ-39). Correlations between DASH scores and PDD risk factors were examined. PD patients with mild cognitive impairment (PD-MCI) were additionally split into patients with low and high DASH burden, the latter group additionally stratified by presence of cognitive-driven ADL impairment. DASH-NMS scores differed significantly between PD-MCI and cognitively normal (PD-CN) patients (p = .04), while the DASH-PDQ did not (p = .73). The only significant predictor of the DASH-NMS score was cognitive-driven ADL (p = .01). PD-MCI patients with a high DASH burden and more cognitive ADL impairment presented with worse global cognition than patients with a low burden (p = .045). Our results show that the DASH-NMS is superior to the DASH-PDQ score, related to the severity of cognitive impairment, and strongly influenced by cognitive-driven ADL impairment. Presence of DASH symptoms and cognitive-ADL in PD-MCI patients may define a risk group for PDD conversion. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Low plasma thiamine and phosphate in male patients with Parkinson's disease is associated with mild cognitive impairment

Thiamine deficiency (TD) and phosphate depletion increase the risk for cognitive disturbances. This study investigates whether plasma levels of thiamine (P-THIAM), thiamine-monophosphate (P-TMP), and phosphate (P-PHOS) are associated with mild cognitive decline (MCI) in patients with Parkinson's disease (PD). This case-control study includes baseline data from a cohort of newly diagnosed patients identified in the New Parkinsonism in Umeå study (NYPUM) (N=75) and an age and sex matched control group (n=24). Mini Nutritional Assessment (MNA-score) and concentrations of P-THIAM, P-TMP, and P-PHOS at baseline were compared between PD patients with mild cognitive impairment (PD-MCI) and PD patients with normal cognition (PD-NC). Neuropsychological assessments of MCI were performed at time of diagnosis. Compared to patients with NC, patients with MCI had lower levels of P-THIAM and P-TMP as well as lower scores on both the Mini Mental State Examination (MMSE) and MNA-screening test. In addition, patients with MCI were older and had more motor problems. The multiple logistic regressions adjusted for age and sex revealed that higher levels of P-THIAM and the MNA-total score were associated with a lower risk of having MCI. Higher MNA-total score and higher P-THIAM and P-PHOS concentrations decreased the risk of MCI in male patients, but not in female patients. The decreased risk of MCI with higher P-TMP levels was lost after adding age and sex to the model. Bivariate correlations between P-PHOS and P-TMP were shown for the total PD population and controls as well as for males with MCI (r=0.533; n=22; p=0.011), but not for males with NC (r=0.314; n=19; p=0.204). An inverse partial correlation (adjusted for age, sex and UPDRS III) was shown for P-THIAM and MNA-total (r=-0.315,p=0.009) and -final (part II) (r=-0.395,p=0.001) score for the PD population (n=75). Higher P-THIAM and P-PHOS concentrations and higher MNA-total score were associated with a lower risk of MCI in male PD patients, findings that indicate that nutritional factors may influence cognitive function in males in the early phase of PD.

Primary disruption of the default mode network subsystems in drug-naïve Parkinson's disease with mild cognitive impairments.

Mild cognitive impairment (MCI) in Parkinson's disease (PD) is related to the disrupted connectivity in networks involved in cognition, primarily in the default mode network (DMN). The DMN contains a midline core and two distinct subsystems (dorsal medial prefrontal cortex (DMPFC) and medial temporal lobe (MTL) subsystems). The strength of functional connectivity (FCS) in intra- and inter-subsystems of DMN and the regional FCS were compared between any two groups from 28 drug-naïve PD patients with MCI (PD-MCI), 19 drug-naïve PD patients with cognitive unimpaired (PD-CU), and 28 age- and sex-matched healthy controls (HCs) by using the nonparametric permutation method (10,000 permutations) with age, sex, and education as covariates and False Discovery Rate (FDR) correction. For intra-subsystems, the decreased FCS was only detected in the DMPFC subsystem of PD-MCI patients compared with HCs. For inter-subsystems, PD-MCI patients displayed decreased FCS between the posterior cingulate cortex (PCC) and DMPFC subsystem compared with HCs. Furthermore, the temporal parietal junction (TPJ) in the DMPFC subsystem showed decreased regional FCS in the PD-MCI subgroup relative to the HC group. No significant change of FCS was found between PD-MCI and PD-CU patients, and between PD-CU patients and HCs. The sum of FCS values within the DMPFC subsystem and FCS values between the PCC and DMPFC subsystem had a significant power to distinguish PD-MCI patients from PD-CU patients (area under curve (AUC) = 0.703). The DMPFC subsystem was predominantly disrupted in the PD-MCI subgroup and may have the potential to discriminate PD with MCI.

Alterations of regional homogeneity in Parkinson's disease with mild cognitive impairment: a preliminary resting-state fMRI study.

Mild cognitive impairment (MCI) is commonly observed in Parkinson's disease (PD), even in the early stages. However, the neural substrates of cognitive impairment in PD remain unclear. The aim of the current study was to investigate the change of local brain function in PD patients with MCI. Fifty patients with PD, including 25 PD patients with MCI (PD-MCI) and 25 PD patients with normal cognition (PD-NC), and 25 age- and sex-matched healthy controls (HC) were enrolled. Conventional magnetic resonance imaging (MRI), 3D structural images, and resting state-functional MRI (rs-fMRI) were performed in all subjects. Regional homogeneity (ReHo) was measured based on the rs-fMRI images to investigate the altered local brain functions. Brain regions with decreased ReHo were located in the left posterior cerebellar lobe in PD sub-groups compared to the HC group, and the brain regions with increased ReHo were located in the limbic lobe (right precuneus/bilateral middle cingulate cortex) in PD-MCI compared with HC group. PD-MCI presented with increased ReHo in the bilateral precuneus/left superior parietal lobe and decreased ReHo in the left insula compared to PD-NC. ReHo values for the left precuneus were negatively related to neuropsychological scores, and ReHo values for the left insula were positively related to neuropsychological scores in PD subjects. The present study demonstrated abnormal spontaneous synchrony in the left insula and left precuneus in patients with PD-MCI compared to PD-NC, which might provide a novel insight into the diagnosis and clinical treatment of cognitive impairment in PD.