PD Patients With Mild Cognitive Impairment Patients Research Articles

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.

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.

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).

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.

Changes of brain structural network connection in Parkinson's disease patients with mild cognitive dysfunction: a study based on diffusion tensor imaging.

Previous studies have found that white matter (WM) alterations might be correlated in Parkinson's disease (PD) patients with cognitive impairment. This study aimed to investigate WM structural network connectome alterations in PD patients with mild cognitive impairment (PD-MCI) and assess the relationship between cognitive impairment and structural topological network changes in PD patients. All 31 healthy controls (HCs) and 71 PD patients (43 PD-NC and 28 PD-MCI) matched for age, sex and education underwent 3.0 T MRI and diffusion tensor imaging (DTI) scan. Graph theoretical analyses and network-based statistical (NBS) analyses were performed to identify the structural WM networks and subnetwork changes in PD-MCI. PD-MCI patients showed significantly decreased global efficiency (Eglob) and increased shortest path length (Lp) compared with the HC group. Several nodal efficiencies showed significant differences in multiple brain regions among the three groups. The nodal efficiency of the orbitofrontal part was closely related to the overall cognitive ability and multiple sub-cognitive domains. Moreover, NBS analyses identified eight one-connect subnetworks, three two-connect subnetworks and two multi-connect subnetworks with reduced connectivity that characterizes the WM structural organization in PD-MCI patients. The two multi-connect subnetworks were located on the bilateral lobe, and both were centered on the orbitofrontal part. This study provided new evidence that PD with cognitive dysfunction is associated with WM structural alterations. The nodal efficiency and sub-network analyses focusing on the orbitofrontal part might provide new ideas to explore the physiological mechanism of PD-MCI.

Why Is Aging a Risk Factor for Cognitive Impairment in Parkinson's Disease?-A Resting State fMRI Study.

Using resting-state functional MRI (rsfMRI) data of younger and older healthy volunteers and patients with Parkinson's disease (PD) with and without mild cognitive impairment (MCI) and applying two different analytic approaches, we investigated the effects of age, pathology, and cognition on brain connectivity. When comparing rsfMRI connectivity strength of PD patients and older healthy volunteers, reduction between multiple brain regions in PD patients with MCI (PD-MCI) compared with PD patients without MCI (PD-non-MCI) was observed. This group difference was not affected by the number and location of clusters but was reduced when age was included as a covariate. Next, we applied a graph-theory method with a cost-threshold approach to the rsfMRI data from patients with PD with and without MCI as well as groups of younger and older healthy volunteers. We observed decreased hub function (measured by degree and betweenness centrality) mainly in the medial prefrontal cortex (mPFC) in older healthy volunteers compared with younger healthy volunteers. We also found increased hub function in the posterior medial structure (precuneus and the cingulate cortex) in PD-non-MCI patients compared with older healthy volunteers and PD-MCI patients. Hub function in these posterior medial structures was positively correlated with cognitive function in all PD patients. Together these data suggest that overlapping patterns of hub modifications could mediate the effect of age as a risk factor for cognitive decline in PD, including age-related reduction of hub function in the mPFC, and recruitment availability of the posterior medial structure, possibly to compensate for impaired basal ganglia function.

Neuroinflammation Mediators are Reduced in Sera of Parkinson's Disease Patients with Mild Cognitive Impairment.

Cognitive impairment is common in Parkinson's disease (PD) and PD patients with mild cognitive impairment (PD-MCI) are at increased risk of developing Parkinson's disease dementia (PDD). Reliable biomarkers are required for objective identification of cognitive decline in PD. In this pilot study, serum levels of well-known mediators of neuroinflammation were measured in PD patients with or without MCI to find out the involvement of neuroinflammation and microglial activation in PD-MCI. 36 PD-MCI, 25 PD patients with normal cognition (PD-NC) and 19 healthy controls were recruited. Serum levels of NLR family pyrin domain containing 1 (NLRP1), NLRP3, caspase-1, NF-kB, IL-1b and IL-18 were measured by ELISA and a panel of neuropsychological tests was administered. PD-MCI patients showed significantly reduced levels of NF-kB, IL-1b and IL-18, whereas NLRP1, NLRP3 and caspase-1 levels were comparable among PD-NC and PD-MCI patients. IL-18 levels were positively correlated with Addenbrooke's Cognitive Examination-Revised and Symbol Digit Modalities Test scores. Levels of several microglial activation mediators are reduced in PD-MCI patients inferring a protective role to certain inflammation factors against cognitive decline in PD.

Brain degeneration in Parkinson's disease patients with cognitive decline: a coordinate-based meta-analysis.

Cognitive decline in Parkinson's disease (PD) is a common sequela of the disease, with its severity increasing as the neurodegenerative process advances. The present meta-analysis used anisotropic effect size seed-based d mapping software to perform analyses using both functional and structural brain imaging data. The analyses were between PD patients with mild cognitive impairment (PD-MCI) and PD patients with dementia (PDD) compared to PD cognitively unimpaired patients (PD-CU) and PD patients without dementia (PD-ND) respectively. Thirty-four studies were found and split into three analyses: 405 PD-MCI patients compared to 559 PD-CU patients from 1) 15 studies with structural imaging modalities and 2) eight studies with functional imaging modalities, as well as 178 PDD patients compared to 278 PD-ND patients (which includes both PD-CU and PD-MCI) in 3) 11 studies with structural imaging modalities. Statistical threshold was set to uncorrected p < 0.001. We found several brain regions that differed between PD-MCI and PD-CU patients: the left insula, bilateral dorsolateral prefrontal cortex, left angular gyrus, midcingulate cortex, and right supramarginal gyrus. The brain regions identified in the PD-MCI analyses are associated with the somatosensory network and executive processing. In PDD patients, the bilateral insula and right hippocampus were found as regions of structural atrophy. The insula was found in both structural analyses of PD-MCI and PDD, with unilateral insula involvement in PD-MCI extending to bilateral insula involvement in PDD. The results found both a spectrum of increasing brain atrophy in PD cognitive impairment and supports the existence of sub-typing in PD-MCI.

Dynamic functional connectivity in Parkinson's disease patients with mild cognitive impairment and normal cognition.

The objective was to assess dynamic functional connectivity (FC) and local/global connectivity in Parkinson's disease (PD) patients with mild cognitive impairment (PD-MCI) and with normal cognition (PD-NC).The sample included 35 PD patients and 26 healthy controls (HC). Cognitive assessment followed an extensive neuropsychological battery. For resting-state functional MRI (rs-fMRI) analysis, independent component analysis (ICA) was performed and components were located in 7 networks: Subcortical (SC), Auditory (AUD), Somatomotor (SM), visual (VI), cognitive-control (CC), default-mode (DMN), and cerebellar (CB). Dynamic FC analysis was performed using the GIFT toolbox. FC differences between groups in each FC state were analysed with the network-based statistic (NBS) approach. Finally, a graph-theoretical analysis for local/global parameters was performed.The whole sample showed 2 dynamic FC states during the rs-fMRI. PD-MCI patients showed decreased mean dwell time in the hypo-connectivity state (p = 0.030) and showed increased number of state transitions (p = 0.007) compared with the HC. In addition, in the hypo-connectivity state, PD-MCI patients showed reduced inter-network FC between the SM-CC, SM-VI, SM-AUD, CC-VI and SC-DMN compared with the HC (p < 0.05-FDR). These FC alterations in PD-MCI were accompanied by graph-topological alterations in nodes located in the SM network (p < 0.001). In contrast, no differences were found between the PD-NC and HC.Findings suggest the presence of dynamic functional brain deteriorations in PD-MCI that are not present in PD-NC, showing the PD-MCI group dynamic FC dysfunctions, reduced FC mostly between SM-CC networks and graph-topological deteriorations in the SM network. A dynamic FC approach could be helpful to understand cognitive deterioration in PD.

Cortical thinning correlates of changes in visuospatial and visuoperceptual performance in Parkinson's disease: A 4-year follow-up

BackgroundGrowing evidence highlights the relevance of posterior cortically-based cognitive deficits in Parkinson's disease (PD) as possible biomarkers of the evolution to dementia. Cross-sectional correlational studies have established a relationship between the degree of atrophy in posterior brain regions and visuospatial and visuoperceptual (VS/VP) impairment. The aim of this study is to address the progressive cortical thinning correlates of VS/VP performance in PD. MethodsForty-four PD patients and 20 matched healthy subjects were included in this study and followed for 4 years. Tests used to assess VS/VP functions included were: Benton's Judgement of Line Orientation (JLOT), Facial Recognition (FRT), and Visual Form Discrimination (VFDT) Tests; Symbol Digit Modalities Test (SDMT); and the Pentagon Copying Test (PCT). Structural magnetic resonance imaging data and FreeSurfer were used to evaluate cortical thinning evolution. ResultsPD patients with normal cognition (PD-NC) and PD patients with mild cognitive impairment (PD-MCI) differed significantly in the progression of cortical thinning in posterior regions. In PD-MCI patients, the change in VS/VP functions assessed by PCT, JLOT, FRT, and SMDT correlated with the symmetrized percent change of cortical thinning of occipital, parietal, and temporal regions. In PD-NC patients, we also observed a correlation between changes in FRT and thinning in parieto-occipital regions. ConclusionIn this study, we establish the neuroanatomical substrate of progressive changes in VS/VP performance in PD patients with and without MCI. In agreement with cross-sectional data, VS/VP changes over time are related to cortical thinning in posterior regions.

Changes of brain structure in Parkinson's disease patients with mild cognitive impairment analyzed via VBM technology.

To analyze changes in cerebral grey matter volume and white matter density in non-dementia Parkinson's disease patients using voxel-based morphometry (VBM) technology; to investigate features of brain structure changes in Parkinson's disease patients with mild cognitive impairment (PD-MCI), and reveal their intrinsic pathological changes. Based on the diagnostic criteria of PD-MCI, 23 PD-MCI patients, 23 Parkinson's disease patients with normal cognition (PD-NC), and 21 age- and gender-matched healthy people were recruited for the study. Scans were performed on all subjects on a 3.0T MR scanner to obtain brain structural magnetic resonance images. Images were preprocessed using the VBM8 tool from SPM8 software package on the Matlab R2008a platform, and data were then analyzed using the SPM statistical software package to compare the differences of grey matter volume and white matter density between groups, and to evaluate the brain structural changes corresponding to the overall cognitive function. Compared to the control group, the PD-NC group suffered from grey matter atrophy, mainly found in the prefrontal lobe, limbic lobe and left temporal gyrus. The PD-MCI group suffered from grey matter atrophy found in the frontal lobe, limbic lobe, basal ganglia and cerebellum. Compared to the PD-NC group, the PD-MCI group suffered from grey matter atrophy found in the left-side middle temporal gyrus, inferior temporal gyrus and frontal lobe. The grey matter regions correlated with MMSE score (mainly memory related) including the right cingulate gyrus and the limbic lobe. The grey matter regions correlated with MoCA score (mainly non-memory related) including the frontal lobe, basal ganglia, parahippocampal gyrus, occipital lobe and the cerebellum. Additionally, overall cognitive function in non-dementia PD was mainly located in the frontal and limbic system, and was dominated by subcortical atrophy. Structural changes in PD-MCI patients are associated with overall cognitive function, and the atrophic areas are mainly located in the frontal and limbic system, and are dominated by subcortical atrophy. Moreover, atrophy of limbic lobes is associated with impaired memory, whereas frontal lobe atrophy is associated with executive dysfunction. In addition, the subtle brain structure of the PD early cognitive impairment stage and PD-MCI stage can be detected via VBM technology, and thus, local brain atrophy may be a neuroimaging marker for the early diagnosis of PD-MCI.