PD Patients With Normal Cognition Research Articles

Neuroimaging and Neuropsychological Performance in Parkinson's Disease Patients with Normal Cognition: A Systematic Review

Introduction: Cognitive decline is one of Parkinson's disease's (PD) non-motor symptoms that is most frequently observed. Patients with PD exhibit quick cognitive decline in a variety of cognitive domains, particularly in the areas of executive functions, attention, language, memory, and visuospatial abilities. The scope of PD patients with normal cognition (PD-NC) and its relationship to specific regions of the brain as shown by neuroimaging, have not received much attention in the literature.
 Objective: This review was to summarise the existing literature that explored cognitive performance in PD-NC using different neuroimaging techniques.
 Methods: A comprehensive search was conducted on PubMed and Web of Science databases. This review focused on papers that investigated neuroimaging and neuropsychological performance in patients with PD. A total of 17 articles have met the criteria.
 Results: The findings of this review were that executive functions appear to be the most critical cognitive domain to be damaged in PD-NC. Global cognitive ability was found to have insignificant decline overall between PD-NC and healthy controls (HC). Attention and executive functions were associated with the prefrontal cortex. Memory was mainly associated with hippocampal atrophy. Language was associated with cerebrospinal fluid and grey matter. Visuospatial ability was associated with the anterior cingulate cortex.
 Conclusion: This review illustrated that PD-NC seemed to experience different cognitive patterns and neuroanatomical changes compared with HC. These results suggested that PD-NC may develop specific cognitive impairments associated with specific brain regions. Therefore, it indicated that PD-NC may need to have specific treatments tailored to their needs.

4 Compensatory Functional Activation During Motion Discrimination in Parkinson’s Disease

Objective:PD patients commonly exhibit executive dysfunction early in the disease course which may or may not predict further cognitive decline over time. Early emergence of visuospatial and memory impairments, in contrast, are more consistent predictors of an evolving dementia syndrome. Most prior studies using fMRI have focused on mechanisms of executive dysfunction and have demonstrated that PD patients exhibit hyperactivation that is dependent on the degree of cognitive impairment, suggestive of compensatory strategies. No study has evaluated whether PD patients with normal cognition (PD-NC) and PD patients with Mild Cognitive Impairment (PD-MCI) exhibit compensatory activation patterns during visuospatial task performance.Participants and Methods:10 PD-NC, 12 PD-MCI, and 14 age and sex-matched healthy controls (HC) participated in the study. PD participants were diagnosed with MCI based on the Movement Disorders Society Task Force, Level II assessment (comprehensive assessment). Functional magnetic resonance imaging (fMRI) was performed during a motion discrimination task that required participants to identify the direction of horizontal global coherent motion embedded within dynamic visual noise under Low and High coherence conditions. Behavioral accuracy and functional activation were evaluated using 3 * 2 analyses of covariance (ANCOVAs) (group [HC, PD-NC, PD-MCI] * Coherence [High vs. Low]) accounting for age, sex, and education. Analyses were performed in R (v4.1.2(Team, 2013)).Results:PD-MCI (0.702± 0.269) patients exhibited significantly lower accuracy on the motion discrimination task than HC (0.853 ± 0.241; p = 0.033) and PD-NC (0.880 ± 0.208; p =0.039). A Group * Coherence interaction was identified in which several regions, including orbitofrontal, posterior parietal and occipital cortex, showed increased activation during High relative to Low coherence trials in the PD patient groups but not in the HC group. HC showed default mode deactivation and frontal-parietal activation during Low relative to High coherence trials that was not evident in the patient groups.Conclusions:PD-MCI patients exhibited worse visuospatial performance on a motion discrimination task than PD-NC and HC participants and exhibited hyperactivation of the posterior parietal and occipital regions during motion discrimination, suggesting possible compensatory activation.

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.

Abnormal Neural Activity in Different Frequency Bands in Parkinson's Disease With Mild Cognitive Impairment.

Background: Abnormal spontaneous neural activity is often found in patients with Parkinson’s disease with mild cognitive impairment (PD-MCI). However, the frequency dependence of neuronal interaction activities, especially the fractional amplitude of low-frequency fluctuation (fALFF) and degree centrality (DC), in PD-MCI is still unclear. Thus, this study aimed to explore the frequency dependence of PD-MCI based on fALFF and DC maps.Methods: Twenty-four patients with PD-MCI, 42 PD patients with normal cognition (PD-NC), and 33 healthy controls (HCs) were enrolled. Neuropsychological assessments and resting-state functional MRI (rs-fMRI) were performed. The fALFF and DC values in the conventional, slow4 and slow5 frequency bands were compared among the groups.Results: In the conventional frequency band, the DC value in the left precentral area was decreased in PD-MCI patients, while that in the right fusiform area was increased in PD-NC patients compared with HCs. Regarding fALFFs, both the PD-MCI and PD-NC patients had decreased values in the right precentral area compared with those of the HCs. The fALFFs did not differ between PD-MCI and PD-NC patients. The fALFF results in the slow4 subfrequency band were consistent with those in the conventional frequency band. In the slow5 band, the DC value in the left middle temporal lobe was higher in PD-MCI patients than in PD-NC patients and was positively correlated with the performance of the PD-MCI patients on the Montreal Cognitive Assessment (MoCA). Additionally, both PD-MCI and PD-NC patients showed lower fALFF values in the bilateral putamen than the HCs, and the fALFF in the bilateral putamen was negatively correlated with the Hoehn and Yahr stages of PD-MCI. The fALFF in the left putamen was negatively correlated with the scores of PD-MCI patients on the Movement Disorder Society-Unified Parkinson Disease Rating Scale Part III (MDS-UPRDS-III).Conclusion: Our results suggested that abnormal neuronal activities, such as fALFF and DC, are dependent on frequency in PD-MCI. Some subfrequency bands could distinguish PD-MCI from PD. Our findings may be helpful for further revealing the frequency-dependent resting functional disruption in PD-MCI.

Significant cognitive decline in Parkinson's disease exacerbates the reliance on visual feedback during upper limb reaches

While upper limb reaches are often made in a feed-forward manner, visual feedback during the movement can be used to guide the reaching hand towards a target. In Parkinson's disease (PD), there is evidence that the utilisation of this visual feedback is increased. However, it is unclear if this is due solely to the characteristic slowness of movements in PD providing more opportunity for incorporating visual feedback to modify reach trajectories, or whether it is due to cognitive decline impacting (feed-forward) movement planning ability. To investigate this, we compared reaction times and movement times of reaches to a target in groups of PD patients with normal cognition (PD-NC), mild cognitive impairment (PD-MCI) or dementia (PD-D), to that of controls with normal cognition (CON-NC) or mild cognitive impairment (CON-MCI). Reaches were undertaken with full visual feedback (at a ‘natural’ and ‘fast-as-possible’ pace); with reduced visual feedback of the reaching limb to an illuminated target; and without any visual feedback to a remembered target with eyes closed.The PD-D group exhibited slower reaction times than all other groups across conditions, indicative of less efficient movement planning. When reaching to a remembered target with eyes closed, all PD groups exhibited slower movement times relative to their natural pace with full visual feedback. Crucially, this relative slowing was most pronounced for the PD-D group, compared to the PD-MCI and PD-NC groups, suggesting that substantial cognitive decline in PD exacerbates dependence on visual feedback during upper limb reaches.

Meynert nucleus-related cortical thinning in Parkinson's disease with mild cognitive impairment.

Cognitive impairment in Parkinson's disease (PD) involves the cholinergic system and cholinergic neurons, especially the nucleus basalis of Meynert (NBM/Ch4) located in the basal forebrain (BF). We analyzed associations between NBM/Ch4 volume and cortical thickness to determine whether the NBM/Ch4-innervated neocortex shows parallel atrophy with the NBM/Ch4 as disease progresses in PD patients with cognitive impairment (PD-MCI). We enrolled 35 PD-MCI patients, 48 PD patients with normal cognition (PD-NC), and 33 age- and education-matched healthy controls (HCs), with all participants undergoing neuropsychological assessment and structural magnetic resonance imaging (MRI). Correlation analyses between NBM/Ch4 volume and cortical thickness and correlation coefficient comparisons were conducted within and across groups. In the PD-MCI group, NBM/Ch4 volume was positively correlated with cortical thickness in the bilateral posterior cingulate, parietal, and frontal and left insular regions. Based on correlation coefficient comparisons, the atrophy of NBM/Ch4 was more correlated with the cortical thickness of right posterior cingulate and precuneus, anterior cingulate and medial orbitofrontal lobe in PD-MCI versus HC, and the right medial orbitofrontal lobe and anterior cingulate in PD-NC versus HC. Further partial correlations between cortical thickness and NBM/Ch4 volume were significant in the right medial orbitofrontal (PD-NC: r=0.3, P=0.045; PD-MCI: r=0.51, P=0.003) and anterior cingulate (PD-NC: r=0.41, P=0.006; PD-MCI: r=0.43, P=0.013) in the PD groups and in the right precuneus (r=0.37, P=0.04) and posterior cingulate (r=0.46, P=0.008) in the PD-MCI group. The stronger correlation between NBM/Ch4 and cortical thinning in PD-MCI patients suggests that NBM/Ch4 volume loss may play an important role in PD cognitive impairment.

The corticolimbic structural covariance network as an early predictive biosignature for cognitive impairment in Parkinson's disease

Structural covariance assesses similarities in gray matter between brain regions and can be applied to study networks of the brain. In this study, we explored correlations between structural covariance networks (SCNs) and cognitive impairment in Parkinson’s disease patients. 101 PD patients and 58 age- and sex-matched healthy controls were enrolled in the study. For each participant, comprehensive neuropsychological testing using the Wechsler Adult Intelligence Scale-III and Cognitive Ability Screening Instrument were conducted. Structural brain MR images were acquired using a 3.0T whole body GE Signa MRI system. T1 structural images were preprocessed and analyzed using Statistical Parametric Mapping software (SPM12) running on Matlab R2016a for voxel-based morphometric analysis and SCN analysis. PD patients with normal cognition received follow-up neuropsychological testing at 1-year interval. Cognitive impairment in PD is associated with degeneration of the amygdala/hippocampus SCN. PD patients with dementia exhibited increased covariance over the prefrontal cortex compared to PD patients with normal cognition (PDN). PDN patients who had developed cognitive impairment at follow-up exhibited decreased gray matter volume of the amygdala/hippocampus SCN in the initial MRI. Our results support a neural network-based mechanism for cognitive impairment in PD patients. SCN analysis may reveal vulnerable networks that can be used to early predict cognitive decline in PD patients.

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.

Disrupted Resting-state Functional Connectivity of the Nucleus Basalis of Meynert in Parkinson’s Disease with Mild Cognitive Impairment

The basal nucleus of Meynert (BNM) shows structural abnormalities in Parkinson’s disease with mild cognitive impairment (PD-MCI). However, it is yet unknown whether functional connectivity (FC) in the BNM (BNM-FC) is altered in patients with PD-MCI. Therefore, in this study, we compared the BNM-FC of patients with PD-MCI and PD patients with normal cognition (PD-NC), to evaluate the relationship between the observed differences of BNM-FC and neuropsychological test scores. Three patient groups, namely PD-MCI, PD-NC, and healthy controls (HCs) (n = 22 each) including were recruited for functional magnetic resonance imaging (fMRI) scanning and neuropsychological assessment. Analysis of covariance was used to assess the inter-group differences. The relationships between BNM-FC and results of cognitive tests were evaluated by partial correlation analysis. Multivariate pattern analysis was used to test whether PD-MCI can be distinguished from PD-NC based on the BNM-FC. Classifier performance was assessed through permutation testing. Compared to PD-NC and HCs, PD-MCI showed reduced BNM-FC in the right superior parietal lobe (SPL) and the right postcentral gyrus. Furthermore, a positive correlation was observed between BNM-FC and the clock copying test (CLOX)/auditory verbal learning test (AVLT) immediate recall scores. We found that 86.36% subjects were correctly classified based on the BNM-FC using the leave-one-out cross-validation (LOOCV) method, with a sensitivity of 90.91% and specificity of 81.82%. Our study provides new insights into the neural basis of cognitive dysfunction in PD patients. We also found that BNM-FC can be an effective feature to distinguish PD-MCI from PD-NC.

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.

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.

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.

The Interaction Between Neuroinflammation and β-Amyloid in Cognitive Decline in Parkinson's Disease.

Activated microglia have been reported to play an important role in Parkinson's disease (PD). A more rapid cognitive decline has been associated with deposits of β-amyloid. In this study, the aim was to evaluate the role of brain β-amyloid and its relationship with activated microglia in PD patients with normal and impaired cognition. We studied 17 PD patients with normal cognition (PDn), 12 PD patients with mild cognitive impairment (PD-MCI), and 12 healthy controls (HCs) with [11C] Pittsburgh compound B (PIB) to assess the impact of β-amyloid deposition in the brain on microglial activation evaluated using the translocator protein 18-kDa (TSPO) radioligand [18F]-FEPPA. [11C] PIB distribution volume ratio was measured in cortical and subcortical regions. [18F]-FEPPA total distribution volume values were compared for each brain region between groups to evaluate the effect of PIB positivity while adjusting for the TSPO rs6971 polymorphism. Factorial analysis of variance revealed a significant main effect of PIB positivity in the frontal lobe (F(1, 34) = 7.1, p = 0.012). Besides the frontal (p = 0.006) and temporal lobe (p = 0.001), the striatum (p = 0.018), the precuneus (p = 0.019), and the dorsolateral prefrontal cortex (p = 0.010) showed significant group × PIB positivity interaction effects. In these regions, PD-MCIs had significantly higher FEPPA VT if PIB-positive. Our results indicate an interaction between amyloid-β deposition and microglial activation in PD. Further investigations are necessary to evaluate if amyloid deposits cause neuroinflammation and further neurodegeneration or if increased microglia activation develops as a protective response.

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.

Abnormal Spontaneous Brain Activity in Early Parkinson's Disease With Mild Cognitive Impairment: A Resting-State fMRI Study.

Mild cognitive impairment (MCI) is a common symptom at the baseline of early Parkinson’s disease (PD) diagnosis, but the neural mechanism is unclear. To address the issue, the present study employed resting-state functional magnetic resonance imaging data of 19 drug-naïve PD patients with normal cognition (PD-NC), 10 PD patients with MCI (PD-MCI) and 13 age- and gender-matched healthy controls (HC) from the Parkinson’s progression markers initiative (PPMI) (http://www.ppmi-info.org/), and examined abnormal spontaneous brain activities in the PD-MCI. The pattern of spontaneous brain activity was measured by examining the amplitude of low-frequency fluctuations (ALFF) of blood oxygen level dependent signal. Voxel-wise one-way analysis of covariance and post hoc analyses of ALFF were performed under non-parametric permutation tests in a general linear model among the three groups, with age, gender and data center as additional covariates. Statistical significances in the post hoc analysis were corrected by a small volume correction with a cluster-level threshold of p < 0.05 (n = 10000 permutations, FWE-corrected). Correlations of clinical and neuropsychological assessments [i.e., Unified Parkinson’s Disease Rating Scale (UPDRS) total score, Montreal Cognitive Assessment (MoCA) and cognitive domains] with the regional ALFF were performed in the PD-MCI group. Compared with the HC, both PD groups exhibited reduced ALFF in the occipital area (Calcarine_R/Cuneus_R). Specially, the PD-MCI group additionally exhibited increased ALFF in the opercular part of right inferior frontal gyrus (Frontal_Inf_Oper_R). Comparing with the PD-NC, the PD-MCI group exhibited significantly higher ALFF in the Frontal_Inf_Oper_R and left fusiform gyus (ps < 0.05). The correlation analysis revealed that the ALFF in the Frontal_Inf_Oper_R was positively correlated with the UPDRS total score (p < 0.05), but marginally negatively correlated with the MoCA score. For cognitive domains, the ALFF in the region also showed a significantly negative correlation with the score of SF test (p < 0.01) and a marginally negative correlation with the score of Symbol-Digit Modalities Test. Together, we concluded hyperactivity in the right inferior frontal gyrus in early PD with MCI, suggesting a compensatory recruitment in response to cognitive decline, which may shed light on thought of dementia progression and potentially comprehensive treatment in PD.

Clinical characteristics of cognitive impairment in patients with Parkinson's disease and its related pattern in 18 F-FDG PET imaging.

This study aimed to characterize the clinical features and the related cerebral glucose metabolism pattern of cognitive impairments in Parkinson's disease (PD) with positron emission tomography (PET) imaging. We recruited 168 PD patients and 100 age-matched healthy controls of similar education and gender distribution. All of those enrolled underwent clinical assessment including the unified Parkinson's disease rating scale motor score, Hoehn and Yahr scale, and comprehensive neuropsychological tests including domains of executive function, attention, memory, visuospatial function, and language. Demographics and the results of cognitive measures were compared between patients and healthy controls. Cognition status was classified as PD patients with dementia (PD-D), PD patients with mild cognitive impairment (PD-MCI), or PD patients with normal cognition (PD-NC). In 53 PD patients who underwent 18 F-fluorodeoxyglucose (18 F-FDG) PET imaging, correlations between Z-score values of the different cognitive domains and cerebral 18 F-FDG uptake were assessed using statistical parametric mapping (SPM8) corrected for age and motor severity. A total of 23.2% of PD patients were PD-MCI and 8.9% were PD-D. In the group of PD-MCI, 96.3% showed multiple-domain deficits, with executive function and attention impairment most predominantly involved. All the cognitive domain scores with the exception of language correlated with 18 F-FDG metabolisms, primarily in posterior temporo-parieto-occipital association cortical areas. This study found that cognitive impairment in PD particularly encompasses frontal/executive deficits. Posterior cortical areas, containing multiple neurotransmitters and neural circuits, may play an important role in the pathogenesis of cognitive impairment in PD.

Monoaminergic Markers Across the Cognitive Spectrum of Lewy Body Disease.

Lewy body disorders, including Parkinson's disease (PD), Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB), are characterized by profound central and peripheral monoaminergic dysfunction. To investigate whether these alterations depend on dementia status, we measured cerebrospinal fluid (CSF) and serum monoamine and metabolite levels across subgroups of the cognitive spectrum, and evaluated their marker potential afterwards. In total, 153 subjects were included, of which 43 healthy controls (HC), 28 PD patients with normal cognition (PD-NC), 26 patients with PD and mild cognitive impairment (PD-MCI), 18 PDD patients, and 38 DLB patients. The levels of monoamines and metabolites in paired CSF and serum samples were analyzed applying reversed-phase high-performance liquid chromatography with electrochemical detection. Firstly, when comparing subgroups, CSF 3-methoxy-4-hydroxyphenylglycol (MHPG) levels were found lowest in HC and PD-NC groups and significantly higher in PDD/DLB patients. In addition, CSF 5-hydroxyindoleacetic acid (5-HIAA) levels differed significantly between HC and PD-MCI/PDD, and DLB patients (P≤0.001), but not between HC and PD-NC patients. Secondly, when performing logistic regression, it was shown that particularly CSF/serum MHPG levels and the serum MHPG to noradrenaline (NA) ratio effectively differentiated between HC and (non-)pooled PD subgroups (AUC = 0.914-0.956), and PDD and DLB patients (AUC = 0.822), respectively. Furthermore, CSF 5-HIAA was the most discriminative parameter to differentiate between PD-NC and PD-MCI (AUC = 0.808), and, PD-NC and PDD subgroups (AUC = 0.916). Our data revealed that especially alterations of the noradrenergic neurotransmitter system could distinguish between Lewy body disorder subtypes, pinpointing CSF/serum MHPG and NA as potential stage markers across the cognitive spectrum.

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.

Clinimetric validity of the Trail Making Test Czech version in Parkinson’s disease and normative data for older adults

Objective: The influence of demographic variables on the Trail Making Test (TMT) performance in older individuals and empirical findings on clinical validity in predementia states, such as Parkinson’s disease mild cognitive impairment (PD-MCI), are limited. The principal aim of this study was to add normative data for the Czech population of older adults and explore the clinimetric properties between PD-MCI and PD patients with normal cognition (PD-NC). Method: The study included 125 PD patients classified as 77 PD-MCI and 48 PD-NC and 528 older individuals (60–74 years, further subdivided for normative tables into 60–64, 65–69 and 70–74 age groups) and very old individuals (aged 75–96, further subdivided into 75–79, 80–84, 85–96) cognitively intact Czech adults. Results: Mostly age, to a lesser extent education but not gender, was associated with most TMT basic and derived indices (TMT-B – A). However, the ratio of TMT-B/TMT-A was independent of both age and education. We provide corresponding T-scores that minimize the effect of demographic variables. The results showed a high discriminative validity of TMT basic and derived indices for the differentiation of PD-MCI from PD-NC (all p < .05). The classification accuracy for the differentiation of PD-MCI from controls was optimal for the TMT-B only (80% area under the curve) based on norm adjusted scores. The classification accuracy of the TMT for PD-MCI vs. PD-NC was suboptimal. Conclusions: The cut-offs and normative standards are useful in clinical practice for those working with PD patients and very old adults.