Cognitive performance and neuropsychiatric symptoms in early, untreated Parkinson's disease.
ABSTRACT: This study was undertaken to determine the prevalence and correlates of cognitive impairment (CI) and neuropsychiatric symptoms (NPS) in early, untreated patients with Parkinson's disease (PD).Both CI and NPS are common in PD and impact disease course and quality of life. However, limited knowledge is available about cognitive abilities and NPS.Parkinson's Progression Markers Initiative (PPMI) is a multi-site study of early, untreated PD patients and healthy controls (HCs), the latter with normal cognition. At baseline, participants were assessed with a neuropsychological battery and for symptoms of depression, anxiety, impulse control disorders (ICDs), psychosis, and apathy.Baseline data of 423 PD patients and 196 HCs yielded no between-group differences in demographic characteristics. Twenty-two percent of PD patients met the PD-recommended screening cutoff for CI on the Montral Cognitive Assessment (MoCA), but only 9% met detailed neuropsychological testing criteria for mild cognitive impairment (MCI)-level impairment. The PD patients were more depressed than HCs (P?
Project description:To evaluate the course and predictors of neuropsychiatric symptoms (NPS) and cognition in patients with de novo Parkinson disease (PD).Cross-sectional study of the cohort of de novo, untreated (at enrollment) patients with PD and healthy controls (HCs) from the Parkinson's Progression Markers Initiative. Participants have serial assessments of global cognition and symptoms of depression, anxiety, psychosis, impulse control disorders (ICDs), sleep and wakefulness, apathy, and fatigue. Available data up to 24 months of follow-up were included.The available sample size was as follows: baseline (PD = 423, HCs = 196), 12 months (PD = 261, HCs = 145), and 24 months (PD = 96, HCs = 83). Patients with PD experienced more depression, fatigue, apathy, and anxiety than HCs at all time points, and apathy (p = 0.001) and psychosis (p = 0.003) increased over time in patients with PD. Approximately two-thirds of patients with PD who screened positive for depression at any given visit were not taking an antidepressant. The Montreal Cognitive Assessment score decreased significantly over time in patients with PD (p < 0.001), but the change was comparable to that in HCs. At the 24-month visit, 44% of patients had been on dopamine replacement therapy (DRT) for at least 1 year, and this group reported more incident ICDs (p = 0.009) and excessive daytime sleepiness (p = 0.03).Multiple NPS are more common in de novo, untreated patients with PD compared with the general population, but they also remain relatively stable in early disease, while global cognition slightly deteriorates. In contrast, initiation of DRT is associated with increasing frequency of several other NPS.
Project description:Studies on evoked responses in Parkinson's disease (PD) may be useful for elucidating the etiology and quantitative evaluation of PD. However, in previous studies, the association between evoked responses and detailed motor symptoms or cognitive functions has not been clear. This study investigated the characteristics of the visual (VEF), auditory (AEF), and somatosensory (SEF) evoked magnetic fields in patients with Parkinson's disease (PD), and the correlations between evoked fields and the patient's clinical characteristics, motor symptoms, and cognitive functions. Twenty patients with PD and 10 healthy controls (HCs) were recruited as participants. We recorded VEF, AEF, and SEF, collected clinical characteristics, performed physical examinations, and administered 10 cognitive tests. We investigated differences in the latencies of the evoked fields between patients with PD and HCs. We also evaluated the correlation of the latencies with motor symptoms and cognitive functioning. There were significant differences between the two groups in 6 of the cognitive tests, all of which suggested mild cognitive impairment in patients with PD. The latencies of the VEF N75m, P100m, N145m, AEF P50m, P100m, and SEF P60m components were greater in the patients with PD than in the HCs. The latencies mainly correlated with medication and motor symptoms, less so with cognitive tests, with some elements of the correlations remaining significant after Bonferroni correction. In conclusion, the latencies of the VEF, AEF, and SEF were greater in PD patients than in HCs and were mainly correlated with medication and motor symptoms rather than cognitive functioning. Findings from this study suggest that evoked fields may reflect basal ganglia functioning and are candidates for assessing motor symptoms or the therapeutic effects of medication in patients with PD.
Project description:BACKGROUND:Parkinson's disease (PD) traditionally is characterized by tremor, rigidity, and bradykinesia, although cognitive impairment also is a common symptom. The clinical presentation of PD is heterogeneous and associated with different risk factors for developing cognitive impairment. PD patients with primary akinetic/rigidity (PDAR) are more likely to develop cognitive deficits compared to those with tremor-predominant symptoms (PDT). Because cognitive impairment in PD appears to be related to changes in the default mode network (DMN), this study tested the hypothesis that DMN integrity is different between PDAR and PDT subtypes. METHOD:Resting state fMRI (rs-fMRI) and whole brain volumetric data were obtained from 17 PDAR, 15 PDT and 24 healthy controls (HCs) using a 3T scanner. PD patients were matched closely to HCs for demographic and cognitive variables, and showed no symptoms of dementia. Voxel-based morphometry (VBM) was used to examine brain gray matter (GM) volume changes between groups. Independent component analysis (ICA) interrogated differences in the DMN among PDAR, PDT, and HC. RESULTS:There was decreased activity in the left inferior parietal cortex (IPC) and the left posterior cingulate cortex (PCC) within the DMN between PDAR and both HC and PDT subjects, even after controlling for multiple comparisons, but not between PDT and HC. GM volume differences between groups were detected at a lower threshold (p < 0.001, uncorrected). Resting state activity in IPC and PCC were correlated with some measures of cognitive performance in PD but not in HC. CONCLUSION:This is the first study to demonstrate DMN differences between cognitively comparable PDAR and PDT subtypes. The DMN differences between PD and HC appear to be driven by the PDAR subtype. Further studies are warranted to understand the underlying neural mechanisms and their relevance to clinical and cognitive outcomes in PDAR and PDT subtypes.
Project description:Rapid eye movement (REM) sleep behavior disorder (RBD) may be a risk factor for cognitive impairment in patients with Parkinson's disease (PD). However, little is known regarding the relation between the severity of RBD and the different domains of cognitive impairment. The aim of this study was: (1) to investigate the domains of cognitive impairment in patients with PD and RBD, and (2) to explore risk factors for PD-mild cognitive impairment (PD-MCI) and the relationship between RBD severity and impairment in different cognitive domains in PD.The participants were grouped as follows: PD without RBD (PD-RBD; n = 42), PD with RBD (PD + RBD; n = 32), idiopathic RBD (iRBD; n = 15), and healthy controls (HCs; n = 36). All participants completed a battery of neuropsychological assessment of attention and working memory, executive function, language, memory, and visuospatial function. The information of basic demographics, diseases and medication history, and motor and nonmotor manifestations was obtained and compared between PD-RBD and PD + RBD groups. Particular attention was paid to the severity of RBD assessed by the RBD Questionnaire-Hong Kong (RBDQ-HK) and the RBD Screening Questionnaire (RBDSQ), then we further examined associations between the severity of RBD symptoms and cognitive levels via correlation analysis.Compared to PD-RBD subjects, PD + RBD patients were more likely to have olfactory dysfunction and their Epworth Sleepiness Scale scores were higher (P < 0.05). During neuropsychological testing, PD + RBD patients performed worse than PD-RBD patients, including delayed memory function, especially. The MCI rates were 33%, 63%, 33%, and 8% for PD-RBD, PD + RBD, iRBD, and HC groups, respectively. RBD was an important factor for the PD-MCI variance (odds ratio = 5.204, P = 0.018). During correlation analysis, higher RBDSQ and RBDQ-HK scores were significantly associated with poorer performance on the Trail Making Test-B (errors) and Auditory Verbal Learning Test (delayed recall) and higher RBD-HK scores were also associated with Rey-Osterrieth complex figure (copy) results.When PD-RBD and PD + RBD patients have equivalent motor symptoms, PD + RBD patients still have more olfactory dysfunction and worse daytime somnolence. RBD is an important risk factor for MCI, including delayed memory. Deficits in executive function, verbal delayed memory, and visuospatial function were consistently associated with more severe RBD symptoms.
Project description:<h4>Objective</h4>To determine the frequency and correlates of impulse control and related behavior symptoms in patients with de novo, untreated Parkinson disease (PD) and healthy controls (HCs).<h4>Methods</h4>The Parkinson's Progression Markers Initiative is an international, multisite, case-control clinical study conducted at 21 academic movement disorders centers. Participants were recently diagnosed, untreated PD patients (n = 168) and HCs (n = 143). The outcome measures were presence of current impulse control and related behavior symptoms based on recommended cutoff points for the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease (QUIP)-Short Form.<h4>Results</h4>There were 311 participants with complete QUIP data. Frequencies of impulse control and related behavior symptoms for patients with PD vs HCs were as follows: gambling (1.2% vs. 0.7%), buying (3.0% vs. 2.1%), sexual behavior (4.2% vs. 3.5%), eating (7.1% vs. 10.5%), punding (4.8% vs. 2.1%), hobbyism (5.4% vs. 11.9%), walkabout (0.6% vs. 0.7%), and any impulse control or related behavior (18.5% vs. 20.3%). In multivariable models, a diagnosis of PD was not associated with symptoms of any impulse control or related behavior (p ? 0.10 in all cases).<h4>Conclusions</h4>PD itself does not seem to confer an increased risk for development of impulse control or related behavior symptoms, which further reinforces the reported association between PD medications and impulse control disorders in PD. Given that approximately 20% of patients with newly diagnosed PD report some impulse control or related behavior symptoms, long-term follow-up is needed to determine whether such patients are at increased risk for impulse control disorder development once PD medications are initiated.
Project description:<h4>Introduction</h4>Our study was designed to examine the relationship between Brain-Derived Neurotrophic Factor (BDNF) genotypes (rs6265, Val66Met), BDNF plasma levels, and cognitive impairment in Chinese patients with panic disorder (PD).<h4>Methods</h4>Total 85 patients with PD and 91 healthy controls finally completed all assessments. The severity of panic symptoms and whole anxiety of PD was measured by Panic Disorder Severity Scale-Chinese Version (PDSS-CV) and Hamilton Anxiety Scale (HAMA-14). Montreal Cognitive Assessment (MoCA) and some neurocognitive measures were conducted to evaluate the cognitive performance. All participants were detected for the plasma BDNF levels and BDNF Val66Met polymorphism before assessment and treatment.<h4>Results</h4>No significant differences were found in the BDNF allele frequencies and the BDNF genotype distributions between healthy controls and PD patients. BDNF Met/Met genotype was associated with lower BDNF plasma levels in PD patients, and PD patients with BDNF Met/Met genotype had the lower scores in the attention and speed of processing domains compared to those with Val/Val and Met/Val genotype (p's < .05). Among PD patients, the BDNF plasma levels showed moderate positive correlations with Stroop interference (r = .60, p < .001). Using the MoCA data, the BDNF plasma levels were correlated with delayed memory (r = .50, p < .001), verbal learning (r = .45, p < .001), and total scores of MoCA (r = .51, p < .001).<h4>Conclusions</h4>The BDNF Met/Met genotype may be associated with lower BDNF plasma levels and cognitive impairments in PD patients.
Project description:Background: Cognitive impairment is one of the most frequent and disabling non-motor symptoms in Parkinson disease (PD) and encompasses a continuum from mild cognitive impairment (PD-MCI) to dementia (PDD). The risk factors associated with them are not completely elucidated. Objective: To characterize the presence and clinical presentation of PD-MCI and PDD in patients with idiopathic PD, examining motor and non-motor features and determining factors associated with cognitive impairment. Methods: Multicenter, cross-sectional study in 298 PD patients who underwent clinical [Hoehn and Yahr (HY) staging and Clinical Impression of Severity Index for Parkinson Disease], neurological [Scales for Outcomes in Parkinson's Disease (SCOPA)-Motor], neuropsychological (Mini Mental State Examination, SCOPA-Cognition, Frontal Assessment Battery and Clinical Dementia Rating Scale), neuropsychiatric [SCOPA-Psychiatric complications, SCOPA-Psychosocial (SCOPA-PS), and Hospital Anxiety and Depression Scale (HADS)], and health-related quality of life [Parkinson Disease Questionnaire for quality of life (PDQ-8)] assessment. Movement Disorders Society criteria were applied to classify patients as normal cognition (NC), PD-MCI, and PDD. The association between variables was explored using multivariate binary and multinomial logistic regression models. Results: Seventy-two patients (24.2%) were classified as NC, 82 (27.5%) as PD-MCI, and 144 (48.3%) as PDD. These last two groups reported more psychosocial problems related with the disease (mean SCOPA-PS, 16.27 and 10.39, respectively), compared with NC (7.28) and lower quality-of-life outcomes (PDQ-8 48.98 and 28.42, respectively) compared to NC (19.05). The logistic regression analysis showed that both cognitive impaired groups had a more severe stage of PD measured by HY [odds ratio (OR) for MCI-PD, 2.45; 95% confidence interval (CI), 1.22-4.90; OR for PDD 2.64; 95% CI, 1.17-5.98]. Specifically, age (OR, 1.30; 95% CI, 1.16-1.47), years of education (OR, 0.91; 95% CI, 0.83-0.99), disease duration (OR, 1.19; 95% CI, 1.07-1.32), HADS-D (OR, 1.20; 95% CI, 1.06-1.35), and hallucinations (OR, 2.98; 95% CI, 1.16-7.69) were related to PDD. Conclusions: Cognitive impairment in PD is associated with more severe disease stage, resulting in a global, neuropsychiatric, psychosocial, and quality-of-life deterioration. This study provides a better understanding of the great impact that cognitive impairment has within the natural history of PD and its relationship with the rest of motor and non-motor symptoms in the disease.
Project description:<b>Objective:</b> The effects of the COVID-19 lockdown on subjects with prodromal phases of dementia are unknown. The aim of this study was to evaluate the motor, cognitive, and behavioral changes during the COVID-19 lockdown in Italy in patients with Parkinson's disease (PD) with and without mild cognitive impairment (PD-MCI and PD-NC) and in patients with MCI not associated with PD (MCInoPD). <b>Methods:</b> A total of 34 patients with PD-NC, 31 PD-MCI, and 31 MCInoPD and their caregivers were interviewed 10 weeks after the COVID-19 lockdown in Italy, and changes in cognitive, behavioral, and motor symptoms were examined. Modified standardized scales, including the Neuropsychiatric Inventory (NPI) and the Movement Disorder Society, Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I and II, were administered. Multivariate logistic regression was used to evaluate associated covariates by comparing PD-NC vs. PD-MCI and MCInoPD vs. PD-MCI. <b>Results:</b> All groups showed a worsening of cognitive (39.6%), pre-existing (37.5%), and new (26%) behavioral symptoms, and motor symptoms (35.4%) during the COVID-19 lockdown, resulting in an increased caregiver burden in 26% of cases. After multivariate analysis, PD-MCI was significantly and positively associated with the IADL lost during quarantine (OR 3.9, CI 1.61-9.58), when compared to PD-NC. In the analysis of MCInoPD vs. PD-MCI, the latter showed a statistically significant worsening of motor symptoms than MCInoPD (OR 7.4, CI 1.09-45.44). Regarding NPI items, nighttime behaviors statistically differed in MCInoPD vs. PD-MCI (16.1% vs. 48.4%, <i>p</i> = 0.007). MDS-UPDRS parts I and II revealed that PD-MCI showed a significantly higher frequency of cognitive impairment (<i>p</i> = 0.034), fatigue (<i>p</i> = 0.036), and speech (<i>p</i> = 0.013) than PD-NC. On the contrary, PD-MCI showed significantly higher frequencies in several MDS-UPDRS items compared to MCInoPD, particularly regarding pain (<i>p</i> = 0.001), turning in bed (p = 0.006), getting out of bed (<i>p</i> = 0.001), and walking and balance (<i>p</i> = 0.003). <b>Conclusion:</b> The COVID-19 quarantine is associated with the worsening of cognitive, behavioral, and motor symptoms in subjects with PD and MCI, particularly in PD-MCI. There is a need to implement specific strategies to contain the effects of quarantine in patients with PD and cognitive impairment and their caregivers.
Project description:Cognitive impairment (CI) is a common nonmotor complication of Parkinson's disease (PD), and is associated with significant disability for patients and burden for caregivers. Similar to motor symptoms, the characteristics of CI in PD can be quite variable, both in terms of what cognitive domains are impaired, and the timing of onset and rate of progression. This review will examine the profile of cognitive domain impairments observed in PD, with a focus on early CI (without dementia). We will also discuss possible relationships between specific cognitive domain impairments in PD and pathological processes such as Lewy-related pathology and Alzheimer's disease. It is our hypothesis that the specific characteristics of CI observed in individual PD patients provide clues to the underlying pathological processes, and that understanding the biological basis of this clinical phenomenon will assist in directing disease-specific treatments. Given the high lifetime risk for CI in PD, it is imperative that we improve our understanding and treatments for this common and disabling problem in PD.
Project description:INTRODUCTION:Past studies have shown that a large portion of individuals with Parkinson's disease (PD) and mild cognitive impairment (MCI) will revert to a cognitively intact (CI) status in the future. Aging studies have shown that individuals who revert from MCI to CI are at increased risk for reconverting to MCI or dementia in the future. The current study examined if individuals who revert from PD-mild cognitive impairment (PD-MCI) to CI will be at increased risk for future PD-MCI and Parkinson's disease dementia (PDD). METHOD:The study utilized data from the Parkinson's Progression Markers Initiative (PPMI). The sample included 364 newly diagnosed PD participants who were followed annually for up to 4 years. Based on the first and second assessments, we identified individuals who were CI at each assessment (CI-Stable) and individuals who were PD-MCI at baseline but then reverted to CI (Reversion). Analyses examined if participants in the Reversion group were at greater risk, relative to the CI-Stable group, for cognitive impairment at future assessments. RESULTS:Participants in the Reversion group were at greater risk for future cognitive impairment (PD-MCI or PDD) at the 2nd, 3rd and 4th annual follow-up, relative to the CI-Stable group. The Reversion group continued to be at increased risk for future cognitive impairment when adjusting for age, gender, education, depressive symptoms, and motor severity. CONCLUSION:A large proportion of individuals with PD-MCI will not show evidence of cognitive impairment within a year. However, these "reverters" continue to be at risk for future development of cognitive impairment.