Cognitive performance and neuropsychiatric symptoms in early, untreated Parkinson's disease.
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ABSTRACT:
SUBMITTER: Weintraub D
PROVIDER: S-EPMC4855523 | biostudies-literature | 2015 Jun
REPOSITORIES: biostudies-literature
Publications
Cognitive performance and neuropsychiatric symptoms in early, untreated Parkinson's disease.
Weintraub Daniel D Simuni Tanya T Caspell-Garcia Chelsea C Coffey Christopher C Lasch Shirley S Siderowf Andrew A Aarsland Dag D Barone Paolo P Burn David D Chahine Lama M LM Eberling Jamie J Espay Alberto J AJ Foster Eric D ED Leverenz James B JB Litvan Irene I Richard Irene I Troyer Matthew D MD Hawkins Keith A KA
Movement disorders : official journal of the Movement Disorder Society 20150304 7
<h4>Unlabelled</h4>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).<h4>Background</h4>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.<h4>Methods</h4>Parkinson's Progression Markers Initiative (PPMI) is a multi-site study of early, untreated PD pati ...[more]
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Project description:Parkinson's disease (PD) is characterized by overlapping motor, neuropsychiatric, and cognitive symptoms. Worse performance in one domain is associated with worse performance in the other domains. Commonality analysis (CA) is a method of variance partitioning in multiple regression, used to separate the specific and common influence of collinear predictors. We apply, for the first time, CA to the functional connectome to investigate the unique and common neural connectivity underlying the interface of the symptom domains in 74 non-demented PD subjects. Edges were modeled as a function of global motor, cognitive, and neuropsychiatric scores. CA was performed, yielding measures of the unique and common contribution of the symptom domains. Bootstrap confidence intervals were used to determine the precision of the estimates and to directly compare each commonality coefficient. The overall model identified a network with the caudate nucleus as a hub. Neuropsychiatric impairment accounted for connectivity in the caudate-dorsal anterior cingulate and caudate-right dorsolateral prefrontal-right inferior parietal circuits, while caudate-medial prefrontal connectivity reflected a unique effect of both neuropsychiatric and cognitive impairment. Caudate-precuneus connectivity was explained by both unique and shared influence of neuropsychiatric and cognitive symptoms. Lastly, posterior cortical connectivity reflected an interplay of the unique and common effects of each symptom domain. We show that CA can determine the amount of variance in the connectome that is unique and shared amongst motor, neuropsychiatric, and cognitive symptoms in PD, thereby improving our ability to interpret the data while gaining novel insight into networks at the interface of these symptom domains.
| S-EPMC7416059 | biostudies-literature
Project description:BackgroundCertain neuropsychiatric symptoms (NPS), namely apathy, depression, and anxiety demonstrated great value in predicting dementia progression, representing eventually an opportunity window for timely diagnosis and treatment. However, sensitive and objective markers of these symptoms are still missing. Therefore, the present study aims to investigate the association between automatically extracted speech features and NPS in patients with mild neurocognitive disorders.MethodsSpeech of 141 patients aged 65 or older with neurocognitive disorder was recorded while performing two short narrative speech tasks. NPS were assessed by the neuropsychiatric inventory. Paralinguistic markers relating to prosodic, formant, source, and temporal qualities of speech were automatically extracted, correlated with NPS. Machine learning experiments were carried out to validate the diagnostic power of extracted markers.ResultsDifferent speech variables are associated with specific NPS; apathy correlates with temporal aspects, and anxiety with voice quality-and this was mostly consistent between male and female after correction for cognitive impairment. Machine learning regressors are able to extract information from speech features and perform above baseline in predicting anxiety, apathy, and depression scores.ConclusionsDifferent NPS seem to be characterized by distinct speech features, which are easily extractable automatically from short vocal tasks. These findings support the use of speech analysis for detecting subtypes of NPS in patients with cognitive impairment. This could have great implications for the design of future clinical trials as this cost-effective method could allow more continuous and even remote monitoring of symptoms.
| S-EPMC8581700 | biostudies-literature
Project description:Background and Objectives: To explore whether specific Neuropsychiatric Symptoms (NPS) are related to worse performance in particular cognitive domains. Materials and Methods: A cross-sectional analysis of the baseline evaluations of older (≥60 years), cognitively unimpaired (CU) participants from the National Alzheimer's Coordinating Center (NACC) Uniform Data Set was performed. Data were derived from 43 Alzheimer's Disease Research Centers. Cognitively impaired individuals, participants with psychiatric disorders and/or under treatment with antipsychotic, anxiolytic, sedative, or hypnotic agents were excluded. NPS were assessed using the Neuropsychiatric Inventory Questionnaire. The association of NPS with participants' performance on episodic memory, semantic memory, language, attention, processing speed and executive function was analysed using an adjusted (considering important demographic and medical factors) multivariate general linear model. Results: A total of 7179 CU, older, predominantly female, Caucasian, and well-educated participants were included in the present analysis. Among them, 1856 individuals had one or more NPS. Our analysis revealed that moderate/severe anxiety was related to worse performance on semantic memory, attention and executive function, the presence of hallucinations was linked to worse processing speed and executive function scores, while the presence of elation/euphoria and aberrant motor behaviour were associated with poorer attention and language performance, respectively. In the context of a secondary, exploratory analysis, the presence of moderate/severe delusions was related to worse processing speed and executive function performance. Conclusions: The relationship between specific NPS and worse performance in particular cognitive domains could inform the formulation of individualized preventive strategies directed to the ''fortification'' of specific cognitive functions in CU individuals with NPS.
| S-EPMC9694960 | biostudies-literature
Project description:IntroductionCaregiver burden is high among caregivers of PD patients (CPD). Neuropsychiatric symptoms are leading contributors to CPD burden, but whether different symptoms differentially impact domains of caregiver burden is not known. Our objective was to examine which neuropsychiatric symptoms and demographic factors contribute to different domains of caregiver burden in PD.MethodsThis was a cross-sectional online survey study. Participants were recruited from the Fox Insight (FI) study and were eligible if they identified themselves as a CPD. The primary outcome was the Caregiver Burden Inventory (CBI) total score and its 5 sub-domain scores. The Neuropsychiatric Inventory Questionnaire (NPI-Q) assessed caregiver-reported neuropsychiatric symptoms in the care recipient. Multivariable linear regression models were used to characterize the associations between NPI-Q symptom severity scores and CBI scores. Covariates were caregiver age, sex, education, and caregiving duration.ResultsThe sample consisted of 450 CPD, mean age 65.87 (SD 10.39) years, 74% females. After adjusting for covariates, CBI total score was predicted by NPI-Q total score (β = 1.96, p < 0.001); model adjusted R2 = 39.2%. Anxiety severity had the largest effect size [standardized β (sβ) = 0.224] on the time-dependency domain, which was also associated with female sex (sβ = - 0.133) and age (sβ = 0.088). Severity of disinhibition (sβ = 0.218), agitation (sβ = 0.199), and female sex (sβ = 0.104) were associated with greater emotional burden.ConclusionOur findings indicate that demographic characteristics and specific neuropsychiatric symptoms contribute differentially to domains of caregiver burden. Tailored interventions to support CPD are needed.
| S-EPMC8289810 | biostudies-literature
Project description:Introduction: Hyperechogenicity of the substantia nigra (SN+) is a risk marker for Parkinson's disease (PD) which can be detected before the diagnosis. In healthy individuals, SN+ has been associated with slight deficits in specific cognitive functions, suggesting cognitive impairment as a possible pre-diagnostic marker for PD. However, the pattern of cognitive deficits associated with SN+ has not yet been compared with those present in PD. Methods: Data of 262 healthy individuals with normal echogenicity (SN-) and 48 healthy individuals with SN+ were compared with 82 early stage PD patients using the "Consortium to Establish a Registry for Alzheimer's disease" test battery. First, the test clusters (factors) were identified using a principal component analysis (PCA). Mean group performance of cognitive tests belonging to distinct factors, according to the PCA, and single subtest performances were compared using analyses of variance. Second, the number of individuals with abnormal cognitive performances (z-score < -1.0) were compared between groups. Results: Verbal memory, semantic and executive function, and praxis were identified as components of cognitive performances. The SN+ group performed significantly worse than the SN- group in tests assessing semantic and executive function, with a non-significant decrease in verbal memory. On the subtest level, individuals of the SN+ group scored significantly lower than the SN- group on the Boston Naming Test (BNT; p = 0.008). In all subtests, the percentages of PD patients with values below the cut-off for abnormal performance were higher than in the SN- group. Moreover, more individuals from the SN+ group scored below the cut-off in the BNT (SN- = 8.4%, SN+ = 20.8%, p = 0.01) and TMT-B (SN- = 6.9%, SN+ = 16.7%, p = 0.02), compared to the SN- group. Conclusion: This study confirms poorer performance of healthy individuals with SN+ compared to SN- in specific cognitive domains. However, against the SN- group, the cognitive profile of the SN+ group was not fully consistent with the profile of early PD patients. Our data argues that cognitive impairment associated with SN+ might differ slightly from that seen in early PD. Compensational mechanisms in the early phases of neurodegeneration, and the fact that only a subgroup of SN+ will develop PD, may partly explain these differences.
| S-EPMC5108760 | biostudies-literature
Project description:BackgroundNeuropsychiatric 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.ObjectivesDetermine if neuropsychiatric symptoms are useful markers of PDD risk.Methods328 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.ResultsThe 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.ConclusionsCognitive 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.
| S-EPMC8015884 | biostudies-literature
Project description:Background: Parkinson's disease (PD) is now known to be a multisystemic heterogeneous neurodegenerative disease, including a wide spectrum of both motor and non-motor symptoms. PD patients' management must encompass a multidisciplinary approach to effectively address its complex nature. There are still challenges in terms of treating axial (gait, balance, posture, speech, and swallowing) and cognitive symptoms that typically arise with disease progression becoming poorly responsive to dopaminergic or surgical treatments. Objective: The objectives of the study are to further establish the presentation of axial and cognitive symptoms in early PD [Hoehn and Yahr (H&Y) scale ? 2] and to discuss the evidence for non-pharmacological approaches in early PD. Results: Mild and subtle changes in the investigated domains can be present even in early PD. Over the last 15 years, a few randomized clinical trials have been focused on these areas. Due to the low number of studies and the heterogeneity of the results, no definitive recommendations are possible. However, positive results have been obtained, with effective treatments being high-intensity treadmill and cueing for gait disturbances, high-intensity voice treatment, video-assisted swallowing therapy for dysphagia, and warm-up exercises and Wii FitTM training for cognition. Conclusions: Considering the association of motor, speech, and cognitive function, future trials should focus on multidisciplinary approaches to combined non-pharmacological management. We highlight the need for a more unified approach in managing these "orphan" symptoms, from the very beginning of the disease. The concept "the sooner the better" should be applied to multidisciplinary non-pharmacological management in PD.
| S-EPMC7546346 | biostudies-literature
Project description:Purpose: Parkinson's disease (PD) patients frequently present with sleep disorders. This study was designed to assess the impact of nonmotor symptoms (NMSs) on sleep quality in early-stage PD patients with and without cognitive dysfunction. Materials and Methods: A sample of 389 early-stage PD patients (modified Hoehn and Yahr score ≤ 2.5, duration ≤ 5 years) was recruited for the present study. The Non-Motor Symptoms Questionnaire (NMS-Quest) was used to screen for global NMSs. Depressive symptoms were assessed using the Hamilton Rating Scale for Depression (HAMD). PD motor symptoms were measured with the Unified PD Rating Scale (UPDRS), part III. The Montreal Cognitive Assessment (MoCA) was used to evaluate global cognitive status, and the PD Sleep Scale (PDSS) was used to quantify sleep quality. Polysomnography (PSG) was used for objective assessment of sleep. Results: In our sample, approximately one-quarter of the PD patients suffered from sleep disturbances (23.7%). Our results also confirmed the high prevalence of cognitive dysfunction in patients with PD (39.8%). In patients with cognitive dysfunction, higher percentage of sleep disorders (34.8 vs. 16.2%, P < 0.01) was observed. They also with lower PDSS score, sleep efficiency (SE) and longer sleep lantency (SL) and wake after sleep onset (WASO) (All P < 0.05). In total, the patients who suffered from NMSs, such as depressive symptoms, anxiety symptoms, urinary tract symptoms and hallucinations/delusions, had poorer sleep quality. Better cognition may predict better sleep quality. In patients with cognitive dysfunction, the NMS-Hallucinations/delusions score was the most important risk factor for sleep disorders. In patients without cognitive dysfunction, NMSs such as anxiety and cognition and medication were related to sleep disorder. Conclusions: NMSs in early-stage PD are highly associated with and are determinants of subjective sleep quality. Future studies should focus on elucidating the pathophysiology of these symptoms.
| S-EPMC7186472 | biostudies-literature
Project description:Apathy, often-unrecognized in Parkinson's Disease (PD), adversely impacts quality-of-life (QOL) and may increase with disease severity. Identifying apathy early can aid treatment and enhance prognoses. Whether feelings related to apathy (e.g., loss of pleasure) are present in mild PD and how apathy and related feelings increase with disease severity is unknown. 120 individuals (M age: 69.0 ± 8.2 y) with mild (stages 1-2, n = 71) and moderate (stages 2.5-4; n = 49) PD were assessed for apathy and apathy-related constructs including loss of pleasure, energy, interest in people or activities, and sex. Correlations were used to determine the association of apathy with apathy-related constructs. Regression models, adjusted for age, cognitive status, and transportation, compared groups for prevalence of apathy and apathy-related feelings. Apathy-related constructs and apathy were significantly correlated. Apathy was present in one in five participants with mild PD and doubled in participants with moderate PD. Except for loss of energy, apathy-related constructs were observed in mild PD at a prevalence of 41% or greater. Strong associations were noted between all apathy-related constructs and greater disease severity. After adjustment for transportation status serving as a proxy for independence, stage of disease remained significant only for loss of pleasure and loss of energy. People with mild PD showed signs of apathy and apathy-related feelings. Loss of pleasure and energy are apathy-related feelings impacted by disease severity. Clinicians should consider evaluating for feelings related to apathy to enhance early diagnosis in individuals who might otherwise not exhibit psychopathology.
| S-EPMC8775593 | biostudies-literature
Project description:Neuropsychiatric symptoms (NPS), such as apathy, irritability and depression, are frequently encountered in patients with Alzheimer's disease (AD). Focal grey matter atrophy has been linked to NPS development. Cerebrovascular disease is common among AD patients and can be detected on MRI as white matter hyperintensities (WMH). In this longitudinal study, the relative contribution of WMH burden and GM atrophy to NPS was evaluated in a cohort of mild cognitive impairment (MCI), AD and normal controls. This study included 121 AD, 315 MCI and 225 normal control subjects from the Alzheimer's Disease Neuroimaging Initiative. NPS were assessed using the Neuropsychiatric Inventory and grouped into hyperactivity, psychosis, affective and apathy subsyndromes. WMH were measured using an automatic segmentation technique and mean deformation-based morphometry (DBM) was used to measure atrophy of grey matter regions. Linear mixed-effects models found focal grey matter atrophy and WMH volume both contributed significantly to NPS subsyndromes in MCI and AD subjects, however, WMH burden played a greater role. This study could provide a better understanding of the pathophysiology of NPS in AD and support the monitoring and control of vascular risk factors.
| S-EPMC7453140 | biostudies-literature