PD-MCI Groups Research Articles

Serum level of YWHAG as a diagnostic marker of cognitive impairment in Parkinson's disease patients.

Identifying reliable biomarkers for early detection and prediction of cognitive impairment in Parkinson's disease (PD) is crucial for optimal patient care. This study set out to investigate the potential of YWHAG as a diagnostic biomarker for cognitive impairment in PD. We enrolled a total of 331 PD patients and selected 241 patients that met the criteria for cognitive impairment analysis. The patients were classified into three groups: PD-NC: PD patients with normal cognition, PD-MCI: PD patients with mild cognitive impairment, and PD-D: PD patients with dementia. ELISA was employed to assess YWHAG expression, as well as the neurofilament light chain (NfL). Additionally, cognitive impairment was evaluated using MoCA scores. Correlation analysis and receiver operating curve analysis (ROC) were performed to clarify the relationship between YWHAG expression and cognitive impairment. Our findings revealed a significant upregulation of YWHAG expression in both the PD-MCI and PD-D groups compared to the PD-NC group. This observation aligned with the elevated expression of NfL in the PD-MCI and PD-D groups. YWHAG and NfL expression levels displayed negative correlations with MoCA scores and positive associations with age. Furthermore, ROC curve analysis demonstrated the diagnostic efficacy of YWHAG expression in distinguishing individuals with PD-NC, PD-MCI, and PD-D. Our findings indicate that YWHAG could serve as a promising biomarker for cognitive impairment in PD. The upregulation of YWHAG expression in PD-MCI and PD-D groups, its association with cognitive impairment, and its correlations with MoCA scores and NfL levels support its potential clinical utility.

17 Grit Predicts Lower Cognitive Fatigue in Persons with Parkinson’s Disease Independent of Cognitive Status

Objective:Fatigue, which can be classified into physical and cognitive subtypes (Schiehser et al., 2012), is a common non-motor symptom in persons with Parkinson’s disease (PD) that has no clear treatment. Cognitive changes, also common in PD (Litvan et al., 2012), may impact how patients perceive fatigue (Kukla et al., 2021). Grit is a personality trait defined as perseverance and passion towards a long-term goal, and is associated with multiple positive outcomes such as lower fatigue levels in healthy individuals (Martinez-Moreno et al., 2021). However, scarce research has examined the relationship between grit and fatigue in persons with PD. Therefore, we aimed to investigate the relationship between fatigue (cognitive and physical) and grit, as well as the impact of cognitive status (i.e., cognitive normal vs. mild cognitive impairment [MCI]) on this relationship in non-demented individuals with PD.Participants and Methods:Participants were 70 non-demented individuals with PD who were diagnosed as either cognitively normal (n=20) or MCI (n=50) based on Level II of the Movement Disorder Society PD-MCI criteria. Participants completed the Modified Fatigue Impact Scale (MFIS), which consists of two subscales (cognitive and physical fatigue) that are combined for a total overall fatigue score. Participants also completed the Grit Scale, which consists of items such as ambition, perseverance, and consistency. ANOVAs were conducted to determine differences in grit between PD-cognitively normal vs PD-MCI groups. Correlations and multiple hierarchical regressions controlling for significant demographics (i.e., age, education, sex), mood (i.e., depression, anxiety) and disease variables (i.e., disease duration, Levodopa equivalent dosage) with backwards elimination were conducted to evaluate the relationship between grit and fatigue (MFIS total score and MFIS cognitive and physical fatigue subscales).Results:There was no significant difference in grit total scores between PD patients who were cognitively normal or MCI (p = .336). Higher grit total scores predicted lower MFIS total (ß = -.290, p = .005) and lower cognitive fatigue (ß = -.336, p < .001) scores in the total sample, above and beyond relevant covariates as well as cognitive status. Grit scores were not significantly associated with physical fatigue (ß = -.206, p = .066). Furthermore, cognitive status was not a significant predictor of fatigue scores in any of the models (all p’s > .28).Conclusions:Findings indicate that higher levels of grit are associated with lower levels of fatigue, specifically cognitive fatigue, in individuals with PD. These results held true for those who were cognitively normal or with MCI, suggesting that grit may impact fatigue in non-demented PD patients regardless of cognitive status. These findings underscore the importance of considering grit when assessing or treating fatigue, particularly cognitive fatigue, in persons with PD.

Cortical atrophy is associated with cognitive impairment in Parkinson's disease: a combined analysis of cortical thickness and functional connectivity.

We aimed to perform a combined analysis of cortical thickness and functional connectivity to explore their association with cognitive impairment in Parkinson's disease (PD). A total of 53 PD and 15 healthy control subjects were enrolled. PD patients were divided into PD with normal cognition (PD-NC, n = 25), PD with mild cognitive impairment (PD-MCI, n = 11), and PD with dementia (PDD, n = 17). In some analyses, the PD-MCI and PDD groups were aggregated to represent "PD patients with cognitive impairment". Cognitive status was assessed with the Mini-Mental State Examination (MMSE). Anatomical magnetic resonance imaging and resting-state functional connectivity analysis were performed in all subjects. First, surface-based morphometry measurements of cortical thickness and voxels with cortical thickness reduction were detected. Then, regions showing reduced thickness were analyzed for changes in resting-state functional connectivity in PD involving cognitive impairment. Our results showed that, compared with PD-NC, patients with cognitive impairment showed decreased cortical thickness in the left superior temporal, left lingual, right insula, and right fusiform regions. PD-MCI patients showed these alterations in the right lingual region. Widespread cortical thinning was detected in PDD subjects, including the left superior temporal, left fusiform, right insula, and right fusiform areas. We found that cortical thinning in the left superior temporal, left fusiform, and right temporal pole regions positively correlated with MMSE score. In the resting-state functional connectivity analysis, we found a decrease in functional connectivity between the cortical atrophic brain areas mentioned above and cognition-related brain networks, as well as an increase in functional connectivity between those region and the cerebellum. Alterations in cortical thickness may result in a dysfunction of resting-state functional connectivity, contributing to cognitive decline in patients with PD. However, it is more probable that the relation between structure and FC would be bidirectional,and needs more research to explore in PD cognitve decline.

Identification of metabolic correlates of mild cognitive impairment in Parkinson's disease using magnetic resonance spectroscopic imaging and machine learning.

To investigate metabolic changes of mild cognitive impairment in Parkinson's disease (PD-MCI) using proton magnetic resonance spectroscopic imaging (1H-MRSI). Sixteen healthy controls (HC), 26 cognitively normal Parkinson's disease (PD-CN) patients, and 34 PD-MCI patients were scanned in this prospective study. Neuropsychological tests were performed, and three-dimensional 1H-MRSI was obtained at 3T. Metabolic parameters and neuropsychological test scores were compared between PD-MCI, PD-CN, and HC. The correlations between neuropsychological test scores and metabolic intensities were also assessed. Supervised machine learning algorithms were applied to classify HC, PD-CN, and PD-MCI groups based on metabolite levels. PD-MCI had a lower corrected total N-acetylaspartate over total creatine ratio (tNAA/tCr) in the right precentral gyrus, corresponding to the sensorimotor network (p = 0.01), and a lower tNAA over myoinositol ratio (tNAA/mI) at a part of the default mode network, corresponding to the retrosplenial cortex (p = 0.04) than PD-CN. The HC and PD-MCI patients were classified with an accuracy of 86.4% (sensitivity = 72.7% and specificity = 81.8%) using bagged trees. 1H-MRSI revealed metabolic changes in the default mode, ventral attention/salience, and sensorimotor networks of PD-MCI patients, which could be summarized mainly as 'posterior cortical metabolic changes' related with cognitive dysfunction.

The Weekly Calendar Planning Activity to Assess Functional Cognition in Parkinson Disease.

The Weekly Calendar Planning Activity (WCPA) may improve understanding of functional cognition in people with Parkinson disease (PwPD) without dementia. We aimed to determine if WCPA performance (a) discriminates between PwPD with and without cognitive impairment and healthy controls and (b) correlates with other indicators of cognition and daily function. This was a cross-sectional study. Parkinson disease (PD) participants without dementia were divided into normal cognition (PD-NC, n = 25) and possible mild cognitive impairment (PD-MCI, n = 21) groups. Their WCPA performance was compared with that of a normative sample (n = 196) and correlated with neuropsychological test performance and self-reported cognition and participation. Both the PD-MCI and PD-NC groups had impaired WCPA performance. WCPA performance correlated with executive function, processing speed, and self-reported cognition and participation. The WCPA can detect functional cognitive deficits in PwPD without dementia and can inform occupational therapy interventions to support functional cognition, occupational performance, and participation in this population.

Neuropsychiatric Symptoms Are Associated with Dementia in Parkinson's Disease but Not Predictive of it.

Neuropsychiatric symptoms in Parkinson's disease (PD) may increase dementia (PDD) risk. The predictive value of these symptoms, however, has not been compared to clinical and demographic predictors of future PDD. Determine if neuropsychiatric symptoms are useful markers of PDD risk. 328 PD participants completed baseline neuropsychiatric and MDS-Task Force-Level II assessments. Of these, 202 non-demented individuals were followed-up over a four-years period to detect conversion to PDD; 51 developed PDD. ROC analysis tested associations between baseline neuropsychiatric symptoms and future PDD. The probability of developing PDD was also modeled as a function of neuropsychiatric inventory (NPI)-total score, PD Questionnaire (PDQ)-hallucinations, PDQ-anxiety, and contrasted to cognitive ability, age, and motor function. Leave-one-out information criterion was used to evaluate which models provided useful information when predicting future PDD. The PDD group experienced greater levels of neuropsychiatric symptoms compared to the non-PDD groups at baseline. Few differences were found between the PD-MCI and PD-N groups. Six neuropsychiatric measures were significantly, but weakly, associated with future PDD. The strongest was NPI-total score: AUC = 0.66 [0.57-0.75]. There was, however, no evidence it contained useful out-of-sample predictive information of future PDD (delta ELPD = 1.8 (SD 2.5)); Similar results held for PDQ-hallucinations and PDQ-anxiety. In contrast, cognitive ability (delta ELPD = 36 (SD 8)) and age (delta ELPD = 11 (SD 5)) provided useful predictive information of future PDD. Cognitive ability and age strongly out-performed neuropsychiatric measures as markers of developing PDD within 4 years. Therefore, neuropsychiatric symptoms do not appear to be useful markers of PDD risk.

A/T/(N) Profile in Cerebrospinal Fluid of Parkinson's Disease with/without Cognitive Impairment and Dementia with Lewy Bodies.

Neuropathological investigations report that in synucleinopathies with dementia, namely Parkinson’s disease (PD) with dementia (PDD) and dementia with Lewy bodies (DLB), the histopathological hallmarks of Alzheimer’s Disease (AD), in particular amyloid plaques, are frequently observed. In this study, we investigated the cerebrospinal fluid (CSF) AD biomarkers in different clinical phenotypes of synucleinopathies. CSF Aβ42/Aβ40 ratio, phosphorylated tau and total tau were measured as markers of amyloidosis (A), tauopathy (T) and neurodegeneration (N) respectively, in 98 PD (48 with mild cognitive impairment, PD-MCI; 50 cognitively unimpaired, PD-nMCI), 14 PDD and 15 DLB patients, and 48 neurological controls (CTRL). In our study, CSF AD biomarkers did not significantly differ between CTRL, PD-MCI and PD-nMCI patients. In PD-nMCI and PD-MCI groups, A-/T-/N- profile was the most represented. Prevalence of A+ was similar in PD-nMCI and PD-MCI (10% and 13%, respectively), being higher in PDD (64%) and in DLB (73%). DLB showed the lowest values of Aβ42/Aβ40 ratio. Higher total tau at baseline predicted a worse neuropsychological outcome after one year in PD-MCI. A+/T+, i.e., AD-like CSF profile, was most frequent in the DLB group (40% vs. 29% in PDD).

Beyond PD-MCI: objectively defined subtle cognitive decline predicts future cognitive and functional changes.

Cognitive impairment is prevalent among individuals with Parkinson's disease (PD). Effort has been made to identify individuals at risk for cognitive decline and dementia. Objectively-defined subtle cognitive decline (Obj-SCD) is a novel classification that may identify individuals at risk for cognitive decline prior to a diagnosis of mild cognitive impairment (MCI). We examined the utility of Obj-SCD criteria to predict future cognitive decline and difficulties with activities of daily living (ADLs) among individuals with PD. The sample included 483 individuals newly diagnosed with PD. Participants were followed for a five-year span with yearly visits where they completed neuropsychological tests. Participants were categorized as cognitively normal (CN), the newly proposed Obj-SCD, PD-MCI or Parkinson's disease dementia (PDD). Analyses determined if utilization of Obj-SCD criteria predicted subsequent cognitive impairment and difficulties with ADLs. At baseline, 372 (77%) participants were classified as CN, 40 (8.3%) classified as Obj-SCD, and 71 (14.7%) classified as PD-MCI. Analyses revealed that relative to the CN group, participants classified as Obj-SCD at baseline, were more likely to develop PD-MCI or PDD within 5years (odds ratio 2.413; 95% confidence interval 1.215-4.792). Furthermore, the Obj-SCD represented an intermediate level of impairment, relative to the CN and PD-MCI groups, on an independent measure of cognition (Montreal Cognitive Assessment) and ADL. Findings provide evidence that Obj-SCD criteria can identify individuals at risk for cognitive decline and impairments in ADL. Obj-SCD criteria may identify individuals at risk for cognitive impairment who are not detected by PD-MCI criteria.

Changes of plasma cGP/IGF-1 molar ratio with age is associated with cognitive status of Parkinson disease.

ObjectiveCognitive impairment is a common feature of Parkinson disease (PD), for which age is a major contributing factor. Insulin‐like growth factor‐1 (IGF‐1) declines with age and contributes to age‐related cognitive impairment in PD. Cyclic glycine‐proline (cGP) is a metabolite of IGF‐1 and normalizes bioavailable IGF‐1. Plasma cGP/IGF‐1 molar ratio that represents bioactive IGF‐1 in circulation, may associate with the cognitive status in PD.MethodsWe examined the association of plasma cGP/IGF‐1 molar ratio with the cognitive scores or age in PD patients with normal cognition (PD‐N, n = 74), mild cognitive impairment (PD‐MCI, n = 71), or dementia (PD‐D, n = 33), and with the cognitive scores in 23 age‐matched healthy controls. Plasma concentrations of IGF‐1, IGF binding protein‐3, and cGP were evaluated using enzyme‐linked immunosorbent assay (ELISA) and high‐performance liquid chromatography‐mass spectrometry (HPLC‐MS), respectively.ResultsThe cGP/IGF‐1 molar ratio was positively correlated with the age of PD‐N group, negatively correlated with the age of PD‐D group, and not associated with the age of PD‐MCI group. Independent of age, the cGP/IGF‐1 molar ratio was positively correlated with the cognitive scores of healthy controls, but not in PD groups.ConclusionOld healthy people with a higher cGP/IGF‐1 molar ratio showed better preserved cognition, possibly due to improved IGF‐1 function. Increased cGP/IGF‐1 molar ratio with age may contribute to cognitive retention in the PD‐N group. The absence or reversal of such association with age in the PD‐MCI and PD‐D groups may indicate the conversion of cognitive status in PD, if confirmed through longitudinal investigations within the individuals with advancing cognitive impairment.

Trait Impulsivity Is Independent of Mild Cognitive Impairment in a Parkinson's Disease Cohort.

Introduction Patients with Parkinson's disease (PD) commonly experience cognitive deficits and some also develop impulse control disorders (ICDs); however, the relationship between impulsivity and cognitive dysfunction remains unclear. This study investigated whether trait impulsivity associates with mild cognitive impairment (MCI), or is altered in a PD patient cohort with MCI. Methods A total of 302 patients with idiopathic PD were recruited sequentially from three Australian Movement Disorder clinics. Based on cognitive scores, participants were divided into two groups, one defined as having mild cognitive impairment (PD-MCI; n = 113) and the other with normal cognitive function (PD-C; n = 189). Trait impulsivity was evaluated using the Barrett Impulsiveness Scale 11 (BIS-11). Total impulsivity scores, as well as subscale scores, were compared between PD-C and PD-MCI groups. Results The PD-MCI cohort had significantly lower scores in all cognitive domains, and mirrored expected clinical differences in medication, motor symptoms, and disease duration, when compared to the PD-C cohort. Self-reported impulsivity was not significantly different between groups, nor was there a difference within first-order subscale scores: attention (p=0.137), cognitive instability (p=0.787), self-control (p=0.503), cognitive complexity (p=0.157), motor impulsivity (p=0.559), or perseverance (p=0.734) between the PD-MCI and PD-C groups. Conclusions These findings suggest that impulsive traits and behaviors are independent of changes in cognitive state and are not altered in PD patients with mild cognitive impairment.

Neuropsychiatric Symptoms in Parkinson’s Disease with and without Mild Cognitive Impairment

Abstract Objective Neuropsychiatric symptoms (NPS) are common clinical features of patients with Parkinson’s disease (PD). However, such symptoms in non-demented PD patients have scarcely been investigated. To address this issue, we describe the neuropsychiatric profile in PD patients with and without Mild Cognitive Impairment (MCI). Participants and Method Eighty non-demented PD patients were included. The patients were divided into two groups depending on the presence or absence of MCI (PD-MCI and PD-nMCI, respectively). MCI diagnosis was made according to the Movement Disorder Society Task Force Level I criteria. NPS were evaluated using the Neuropsychiatric Inventory (NPI). For each domain, the presence and magnitude of symptoms (frequency x severity) was calculated. The total NPI score was also computed, in which higher scores suggest greater behavioral disturbance. Results PD-nMCI (n = 59, 74%) and PD-MCI (n = 21, 26%) groups were similar in the disease stage and years since diagnosis. In contrast with the PD-nMCI group, participants in the PD-MCI group were older. Fourteen PD-MCI (66%) and 45 PD-nMCI (76%) patients reported at least one neuropsychiatric symptom in the previous month. In both groups, the most frequent NPS were sleep disorders, depression, anxiety, apathy, irritability, and disinhibition. Additionally, the proportion of these symptoms between groups did not differ significantly (p > 0.05). There was only a tendency of greater score in the disinhibition subscale in PD-MCI group (p < 0.02). In both groups, NPS were not associated with clinical variables (years since diagnosis, Unified Parkinson's Disease Rating Scale -III) after adjusting for age. Conclusions Preliminary findings suggest that NPS are frequent in PD patients independent of the degree of cognitive impairment, and they may encompass non-motor features of the clinical spectrum of the disease. Further longitudinal investigations are needed to determine whether such symptoms may predict the cognitive decline in these patients.

COWAT Performance of Persons with Alzheimer Dementia, Vascular Dementia, and Parkinson Disease Dementia According to Stage of Cognitive Impairment.

The Controlled Oral Word Association Test (COWAT) evaluates frontal lobe and executive function. Therefore, it can be helpful in differentiating cognitive deficits. However, there are no studies comparing the COWAT performance according to the type and stage of cognitive impairment. To compare performance among persons with Alzheimer dementia (AD), vascular dementia (VaD), and Parkinson disease dementia (PDD) on the COWAT according to stage of cognitive impairment. Retrospective chart review. University hospital rehabilitation psychology center. We reviewed the medical records of 246 persons diagnosed with mild cognitive impairment (MCI) or dementia using the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) and the Korean-Instrumental Activities of Daily Living (K-IADL). Patients were divided into a control group, Alzheimer groups (amnestic mild cognitive impairment [aMCI] + AD), Vascular groups (vascular mild cognitive impairment [VaMCI] + VaD), and Parkinson groups (Parkinson disease-mild cognitive impairment [PD-MCI] + PDD). Total scores (ie, total number of words produced in 60 seconds on the semantic and phonemic fluency tests of the COWAT) were analyzed. Secondary analysis included calculating percentage scores of words produced during each of the four, 15-second segments from the total number of words produced in each trial. All MCI groups scored significantly lower than the control group on both semantic and phonemic fluency tests. Among the dementia groups, the VaD (mean ± SD, 5.6 ± 5.1) and PDD (5.5 ± 5.5) groups' scores were significantly lower and worse than that of the AD (11.0 ± 8.8) group on the phonemic test (P < .001). The difference in percentage scores was most marked between the PD-MCI (17.0 ± 2.2) and PDD (1.2 ± 3.1) groups, followed by the VaMCI (13.3 ± 1.9) and VaD (5.6 ± 1.8) groups on the latter phonemic test (P = .007). The COWAT is a sensitive test of frontal-lobe and executive function impairment in persons with MCI. Decreased verbal output in the last 15 seconds of phonemic fluency test is significantly decreased and impaired in persons with VaMCI and PD-MCI compared to persons with aMCI as they progress to dementia. III.

The difference of mild cognitive impairment in Parkinson's disease from amnestic mild cognitive impairment: Deeper power decrement and no phase-locking in visual event-related responses

Event-related oscillatory responses reflect the cognitive status in many neuropsychiatric conditions including mild cognitive impairment (MCI). In this study, a total of 30 patients with amnestic MCI (aMCI) and 25 patients with MCI of Parkinson's disease (PD-MCI) were compared with 28 aged-, gender-, education-matched healthy control (HC) participants using visual event-related delta, theta, alpha oscillatory responses by methods of event-related spectral perturbation and inter-trial coherence. PD-MCI and aMCI groups commonly share a decreased theta power, but all electrophysiological deviations from the controls were more prominent in PD-MCI than aMCI in all frequency bands. Additionally, decreased phase-locking in all studied frequency bands was encountered only in PD-MCI group, but it was preserved in aMCI. These findings indicate that visual networks in PD-MCI are more severely affected than aMCI. Reduced phase-locking in PD-MCI may possibly relate to dysfunctioning subcortical modulating centers that take a role in the generation of event-related responses.

Altered functional connectivity of the marginal division in Parkinson's disease with mild cognitive impairment: A pilot resting-state fMRI study.

The marginal division (MrD) is an important subcortical center involved in learning and memory. Mild cognitive impairment (MCI) is commonly seen in patients with Parkinson's disease (PD), but the neurobiological basis is yet to be elucidated. To use resting-state functional magnetic resonance imaging (rs-fMRI) to explore the altered functional connectivity (FC) of the MrD in patients with PD-MCI. Prospective pilot study. Twenty-five patients with PD-MCI; 25 PD patients and no cognitive impairment (PD-NCI); and 25 healthy control (HC) participants. 3.0 T GE Healthcare MRI scanner; three-dimensional T1 -weighted fast spoiled gradient recalled echo (3D T1 -FSPGR); rs-fMRI. The MrD was defined using manual delineation, which was the seed point to compute the FC to examine correlations between low-frequency fMRI signal fluctuations in MrD and the whole brain. Between-group comparisons of the rs-fMRI data were computed using two-sample t-tests in a voxelwise manner after controlling for age and sex, to determine the brain regions that showed significant differences in FC with the bilateral MrDs. Correlation analyses were performed for FC values and cognitive abilities in patients with PD. In the PD-MCI group, compared with the PD-NCI group, we observed lesser FC between the MrD bilaterally and right putamen, left insula, left cerebellum, and left thalamus; greater FC between the MrD bilaterally and left middle cingulate cortex, left middle frontal gyrus, left superior frontal gyrus, left supplementary motor area, and left middle/inferior occipital gyrus. Moreover, the strength of FC between the MrD and regions that showed differences between the PD-MCI and PD-NCI groups was significantly correlated with neuropsychological scores in patients with PD. The current study suggests that MrD dysfunction may contribute to MCI in PD. However, the mechanisms underlying this process require further investigation. Level of Evidence 1. Technical Efficacy Stage 2. J. Magn. Reson. Imaging 2019;50:183-192.

Study on the clinical features and related factors of cognitive impairment in Parkinson's disease

Objective To explore the correlated factors and clinical features of cognitive impariment in parkinson's disease (PD). Methods A total of 419 patients with PD were collected from Xiangya Hospital of Centre-South University during Mar 1st, 2017 to Nov 30th, 2017. The cognitive functions of patients were assessed with the Mini-Mental State Examination (MMSE), and the basic information and the motor symptoms of 419 PD patients were selected at the same time. The PD patients were classified into three groups according to the MMSE score: PD with no cognitive impairment (PD-NC), mild cognitive impairment in PD (PD-MCI), and Dementia in PD (PD-D). The data were analyzed by SPSS 20.0. Results There were 156 patients with PD-MCI (37.2%) and 64 patients with PD-D (15.3%). The difference of sex and disease duration among three groups were not statistically significant (P>0.05). The significant difference was found among PD-D, PD-MCI, and PD-NC groups in age of onset, age, educational attainment, Unified Parkinson's disease Rating Scale (UPDRS)-Ⅱscore, UPDRS-Ⅲ score and Hoehn-Yahr stage (P<0.05). There were significant differences among three groups in MMSE score and its items (P<0.01). Logistics regression analysis found that the age of onset, educational attainment, and Hoehn-Yahr stage were the risk factors of cognitive impairment in PD patients (P<0.05). Conclusions Cognitive im-pairment is common in PD patients, and it is relevant to the age of onset, educational attainment and the severity of illness of PD patients. Key words: Parkinson disease/CO; Cognition disorders/CO

Abnormalities of Cortical Neural Synchronization Mechanisms in Subjects with Mild Cognitive Impairment due to Alzheimer’s and Parkinson’s Diseases: An EEG Study

The aim of this retrospective and exploratory study was that the cortical sources of resting state eyes-closed electroencephalographic (rsEEG) rhythms might reveal different abnormalities in cortical neural synchronization in groups of patients with mild cognitive impairment due to Alzheimer's disease (ADMCI) and Parkinson's disease (PDMCI) as compared to healthy subjects. Clinical and rsEEG data of 75 ADMCI, 75 PDMCI, and 75 cognitively normal elderly (Nold) subjects were available in an international archive. Age, gender, and education were carefully matched in the three groups. The Mini-Mental State Evaluation (MMSE) was matched between the ADMCI and PDMCI groups. Individual alpha frequency peak (IAF) was used to determine the delta, theta, alpha1, alpha2, and alpha3 frequency band ranges. Fixed beta1, beta2, and gamma bands were also considered. eLORETA estimated the rsEEG cortical sources. Receiver operating characteristic curve (ROC) classified these sources across individuals. Results showed that compared to the Nold group, the posterior alpha2 and alpha3 source activities were more abnormal in the ADMCI than the PDMCI group, while the parietal delta source activities were more abnormal in the PDMCI than the ADMCI group. The parietal delta and alpha sources correlated with MMSE score and correctly classified the Nold and diseased individuals (area under the ROC = 0.77-0.79). In conclusion, the PDMCI and ADMCI patients showed different features of cortical neural synchronization at delta and alpha frequencies underpinning brain arousal and vigilance in the quiet wakefulness. Future prospective cross-validation studies will have to test these rsEEG markers for clinical applications and drug discovery.

Characteristics of cerebral glucose metabolism in patients with cognitive impairment in Parkinson's disease

To study the relationship between early cognitive impairment symptoms and cerebral glucose metabolism in different brain regions (according to the positron emission tomography (PET) data) in Parkinson's disease (PD) in order to increase the diagnostic and treatment efficacy. Two groups of patients with PD (stage I-III), including 11 patients without cognitive disorders and 13 with mild cognitive impairment (MCI), were examined. The control group included 10 age-matched people with normal cognition. To evaluate cognitive state, the Mini mental state examination (MMSE), the Frontal assessment battery (FAB) and the 'clock drawing test' were used. The regional cerebral glucose metabolism rate (CMRglu) was assessed using PET with 18F-fluorodeoxyglucose (FDG). In PD patients, CMRglu were decreased in the frontal (Brodmann areas (BA) 9, 10, 11, 46, 47), occipital (BA 19) and parietal (BA 39), temporal (BA 20, 37), and cingulate cortex (BA 32) compared to the control group. Cerebral glucose metabolism was decreased in the frontal (BA 8, 9, 10, 45, 46, 47), parietal (BA 7, 39, 40) and cingulate cortex (BA 23, 24, 31, 32) in the group of PD patients with MCI compared to PD patients with normal cognition. Hypometabolism in BA 7, 8, 23, 24, 31, 40 was revealed only in comparison of PD and PD-MCI groups, and did not appear in case of comparison of cognitively normal PD patients with the control group. It is possible to suggest that the mentioned above brain areas were associated with cognitive impairment. The revealed glucose hypometabolism pattern possibly has the diagnostic value for the early and preclinical diagnosis of MCI in PD and control of treatment efficacy.

Power spectra for screening parkinsonian patients for mild cognitive impairment.

ObjectiveMild cognitive impairment in Parkinson’s disease (PD-MCI) is diagnosed based on the results of a standardized set of cognitive tests. We investigate whether quantitative EEG (qEEG) measures could identify differences between cognitively normal PD (PD-CogNL) and PD-MCI patients.MethodsHigh-resolution EEG was recorded in 53 patients with Parkinson’s disease (PD). Relative power in five frequency bands was calculated globally and for ten regions. Peak and median frequencies were determined. qEEG results were compared between groups. Effect sizes of all variables were calculated. The best separating variable was used to demonstrate subject-wise classification.ResultsLower mean values were observed in global alpha1 power and alpha1 power in five brain regions (left hemisphere: frontal, central, temporal, occipital; right hemisphere: temporal, P < 0.05), differentiating between PD-CogNL and PD-MCI groups. Effect sizes were high, ranging from 0.79 to 0.87. Median frequency was 8.56 ± 0.74 Hz and was not different between the groups. The variable with the best subject-wise classification was the power in the alpha1 band in the right temporal region. The area under the corresponding receiver operating characteristic (ROC) curve was 0.72. The optimal classification threshold yielded a sensitivity of 65.9% and a specificity of 66.7%. The positive and negative predictive values were 87.1% and 36.4%, respectively.InterpretationReduction in alpha1 band power in nondemented PD patients, particularly in the right temporal region, is highly indicative of MCI in PD patients. The results might be used to assist in time-efficient diagnosis of PD-MCI and avoid the drawbacks of test–retest effect in repeated neuropsychological testing.

Subthalamic deep brain stimulation: clinical and neuropsychological outcomes in mild cognitive impaired parkinsonian patients.

This observational study reports the long-term follow-up of 184 Parkinson's disease (PD) patients treated with subthalamic deep brain stimulation (STN-DBS), retrospectively analyzing the outcomes of subjects with pre-surgical mild cognitive impairment (MCI) compared to those of patients with normal cognition. Patients were divided into PD-MCI or normal cognition groups at baseline, and then compared after 1, 3, 5 and >5years of follow-up. Subjects assessed by outpatient clinical follow-up evaluation, not performing a complete clinical and neuropsychological follow-up assessment, were separately considered and rated according to their functional autonomy in daily living activities. The MCI prevalence at baseline was 23%, increasing to 34% at 1year and over 40% after 3years. Dementia progressively affected more than 30% of subjects after a median time of 6years in the PD-MCI group and 11years in the normal cognition group (p: 0.028). The mortality risk was slightly higher in PD-MCI patients. Outpatient clinical evaluations showed a progressive increase of subjects completely dependent in the activities of daily living, which ranged from the 11% at 3years to 23% at 5years and 31% at >5years. MCI can be frequently observed in PD patients, possibly influencing the outcome of surgical therapy. Our findings confirm the sustained long-lasting efficacy of STN-DBS on motor functions in both PD-MCI and normal cognition subjects. PD-MCI patients showed a more precocious cognitive impairment, as expected by natural history studies, but no case of dementia was observed early after surgery.

Mild cognitive impairment in patients with Parkinson's disease is associated with increased cortical degeneration

Mild cognitive impairment (MCI) can occur early in the course of Parkinson's disease (PD), and its presence increases the risk of developing dementia. Determining the cortical changes associated with MCI in PD, thus, may be useful in predicting the future development of dementia. To address this objective, 37 patients with PD, divided into 2 groups according to the presence or absence MCI (18 with and 19 without) and 16 matched controls, underwent anatomic magnetic resonance imaging. Corticometry analyses were performed to measure the changes in cortical thickness and surface area as well as their correlation with disease duration. Compared with healthy controls, the PD-MCI group exhibited increased atrophy and changes of local surface area in the bilateral occipital, left temporal, and frontal cortices; whereas the PD non-MCI group exhibited only unilateral thinning and decreased surface area in the occipital lobe and in the frontal cortex. In addition, a comparison between the PD-MCI and PD non-MCI groups revealed increased local surface area in the occipital lobe, temporal lobe, and postcentral gyrus for the cognitively impaired patients. It is noteworthy that, in the PD-MCI group, cortical thickness had a significant negative correlation with disease duration in the precentral, supramarginal, occipital, and superior temporal cortices; whereas, in the PD non-MCI group, such a correlation was absent. The findings from this study reveal that, at the same stage of PD evolution, the presence of MCI is associated with a higher level of cortical changes, suggesting that cortical degeneration is increased in patients with PD because of the presence of MCI.