scholarly journals Neurocognitive Correlates of Apathy and Anxiety in Parkinson's Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Yelena Bogdanova ◽  
Alice Cronin-Golomb

Parkinson's disease (PD) is associated with various nonmotor symptoms including neuropsychiatric and cognitive dysfunction. We examined the relation between apathy, anxiety, side of onset of motor symptoms, and cognition in PD. We hypothesized that PD patients would show different neuropsychiatric and neurocognitive profiles depending on the side of onset. 22 nondemented PD patients (11 right-side onset (RPD) with predominant left-hemisphere pathology, and 11 LPD) and 22 matched healthy controls (NC) were administered rating scales assessing apathy and anxiety, and a series of neuropsychological tests. PD patients showed a higher anxiety level than NC. There was a significant association between apathy, anxiety, and disease duration. In LPD, apathy but not anxiety was associated with performance on nonverbally mediated executive function and visuospatial measures, whereas, in RPD, anxiety but not apathy correlated with performance on verbally mediated tasks. Our findings demonstrated a differential association of apathy and anxiety to cognition in PD.

2013 ◽  
Vol 27 (4) ◽  
pp. 535-545 ◽  
Author(s):  
Yelena Bogdanova ◽  
Alice Cronin-Golomb

Non-motor symptoms such as neuropsychiatric and cognitive dysfunction have been found to be common in Parkinson’s disease (PD) but the relation between such symptoms is poorly understood. We focused on alexithymia, an impairment of affective and cognitive emotional processing, as there is evidence for its interaction with cognition in other disorders. Twenty-two non-demented PD patients and 22 matched normal control adults (NC) were administered rating scales assessing neuropsychiatric status, including alexithymia, apathy, and depression, and a series of neuropsychological tests. As expected, PD patients showed more alexithymia than NC, and there was a significant association between alexithymia and disease stage. Alexithymia was associated with performance on non-verbally mediated measures of executive and visuospatial function, but not on verbally mediated tasks. By contrast, there was no correlation between cognition and ratings of either depression or apathy. Our findings demonstrate a distinct association of alexithymia with non-verbal cognition in PD, implicating right hemisphere processes, and differentiate between alexithymia and other neuropsychiatric symptoms in regard to PD cognition.


2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Zimple Kurlawala ◽  
Paul H. Shadowen ◽  
Joseph D. McMillan ◽  
Levi J Beverly ◽  
Robert P. Friedland

Nonmotor symptoms (NMS) in Parkinson’s disease (PD) can start up to a decade before motor manifestations and strongly correlate with the quality of life. Understanding patterns of NMS can provide clues to the incipient site of PD pathology. Our goal was to systematically characterize the progression of NMS in PD (n = 489), compared to healthy controls, HC (n = 241), based on the sex of the subjects and laterality of motor symptom onset. Additionally, NMS experienced at the onset of PD were also compared to subjects with scans without dopaminergic deficit, SWEDD (n = 81). The Parkinson’s Progression Markers Initiative (PPMI) database was utilized to analyze several NMS scales. NMS experienced by PD and SWEDD cohorts were significantly higher than HC and both sex and laterality influenced several NMS scales at the onset of motor symptoms. Sex Differences. PD males experienced significant worsening of sexual, urinary, sleep, and cognitive functions compared to PD females. PD females reported significantly increased thermoregulatory dysfunction and anxious mood over 7 years and significantly more constipation during the first 4 years after PD onset. Laterality Differences. At onset, PD subjects with right-sided motor predominance reported significantly higher autonomic dysfunction. Subjects with left-sided motor predominance experienced significantly more anxious mood at onset which continued as Parkinson’s progressed. In conclusion, males experienced increased NMS burden in Parkinson’s disease. Laterality of motor symptoms did not significantly influence NMS progression, except anxious mood. We analyzed NMS in a large cohort of PD patients, and these data are valuable to improve PD patients’ quality of life by therapeutically alleviating nonmotor symptoms.


2021 ◽  
Vol 11 (7) ◽  
pp. 841
Author(s):  
Paolo Solla ◽  
Carla Masala ◽  
Ilenia Pinna ◽  
Tommaso Ercoli ◽  
Francesco Loy ◽  
...  

Background: Olfactory dysfunctions and hallucinations are considered common nonmotor symptoms in Parkinson’s disease (PD). Visual and auditory hallucinations are well-known; however, olfactory hallucinations (OHs) are not fully investigated. The aim of this study was to evaluate OHs in PD patients, and their correlation to motor impairment, cognitive abilities, visual and auditory hallucinations, and olfactory and gustatory function. Methods: A sample of 273 patients was enrolled: 141 PD patients (mean age ± SD: 70.1 ± 9.5 years) and 132 healthy controls (mean age ± SD: 69.4 ± 9.6 years). In all patients, the following parameters were evaluated: motor symptoms (UPDRS-III), olfactory function, cognitive abilities, and occurrence of OH, gustatory hallucinations (GHs), and visual/auditory hallucinations. Results: OHs were found only in PD patients with a percentage of 11.3%. Among PD patients with OHs, 2.8% also presented GHs. High significant frequencies of females, the presence of visual/auditory hallucinations, and a high mean UPDRS-III score were found in patients with OHs related to patients without them. Binary logistic regression evidenced the presence of visual/auditory hallucinations and sex as main variables predicting the presence of OHs. Conclusions: Our data indicated that OHs occur frequently in PD patients, especially in women, and often concomitant with visual and auditory hallucinations, without any association with olfactory impairment.


Author(s):  
Gladis Yohana Arboleda-Montealegre ◽  
Roberto Cano-de-la-Cuerda ◽  
César Fernández-de-las-Peñas ◽  
Carlos Sanchez-Camarero ◽  
Ricardo Ortega-Santiago

Background: Parkinson’s disease (PD) is the most common neurodegenerative disorder associated with motor and nonmotor symptoms. Drooling, one of the nonmotor symptoms, can be present in 70–80% of patients with PD. The aim of this paper is to study the characteristics of PD patients with drooling compared to those without in terms of age, gender, disease duration, stage of the disease, swallowing difficulties, and health-related quality of life; methods: a cross-sectional study was conducted. The sample was divided into two groups: PD with drooling (n = 32) and PD without drooling (n = 30). Age, gender, disease duration and Hoehn & Yahr (H & Y) stage, Sialorrhea Clinical Scale for Parkinson’s Disease (SCS-PD), the 10-item Eating Assessment Tool (EAT-10), and the 39-item Parkinson’s Disease Questionnaire (PDQ-39) were compared between groups; Results: 62 individuals with PD, 40 men and 22 women (mean age 73 ± 8 years), were included. Overall, 32 patients reported drooling, and 30 did not exhibit it. The ANCOVA found significant differences between groups for the EAT-10 score (0.83, 95% CI = 5.62–9.03; p = 0.016) and SCS-PD score (1.48, 95% CI = 0.86–6.81; p < 0.001). Analysis of the PDQ-39 scores revealed no significant differences between groups for the PDQ-39 total score (p > 0.057) and in all subscales. The inclusion of gender, age, disease duration, and H & Y as covariates did not influence the results (all p > 0.05). Conclusions: drooling is related to swallowing difficulties assessed with EAT-10 but not with health-related quality of life assessed with PDQ-39 in PD patients with drooling compared to PD patients without it. Age, gender, duration of the disease, and the H & Y state of PD patients with and without drooling seem to be similar.


2021 ◽  
pp. 1-10
Author(s):  
Mechelle M. Lewis ◽  
Richard M. Albertson ◽  
Guangwei Du ◽  
Lan Kong ◽  
Andrew Foy ◽  
...  

Background: Recent randomized clinical trials using hydrophobic statins reported no influence on Parkinson’s disease (PD) clinical progression. Hydrophobicity is a key determinant for blood-brain barrier penetrance. Objective: Investigate a potential effect of statins on PD progression. Methods: Statin use was determined at baseline and subtyped according to hydrophobicity in 125 PD patients participated PD Biomarker Program (PDBP, 2012–2015) at our site. Clinical (N = 125) and susceptibility MRI (N = 86) data were obtained at baseline and 18-months. Movement Disorders Society-Unified PD Rating Scales were used to track progression of non-motor (MDS-UPDRS-I) and motor (MDS-UPDRS-II) symptoms, and rater-based scores (MDS-UPDRS-III) of patients in the “on” drug state. R2 * values were used to capture pathological progression in the substantia nigra. Associations between statin use, its subtypes, and PD progression were evaluated with linear mixed effect regressions. Results: Compared to statin non-users, overall statin or lipophilic statin use did not significantly influence PD clinical or imaging progression. Hydrophilic statin users, however, demonstrated faster clinical progression of non-motor symptoms [MDS-UPDRS-I (β= 4.8, p = 0.010)] and nigral R2 * (β= 3.7, p = 0.043). A similar trend was found for MDS-UPDRS-II (β= 3.9, p = 0.10), but an opposite trend was observed for rater-based MDS-UPDRS-III (β= –7.3, p = 0.10). Compared to lipophilic statin users, hydrophilic statin users also showed significantly faster clinical progression of non-motor symptoms [MDS-UPDRS-I (β= 5.0, p = 0.020)], but R2 * did not reach statistical significance (β= 2.5, p = 0.24). Conclusion: This study suggests that hydrophilic, but not lipophilic, statins may be associated with faster PD progression. Future studies may have clinical and scientific implications.


2018 ◽  
Vol 2018 ◽  
pp. 1-4
Author(s):  
Li Shu ◽  
Dongxiao Liang ◽  
Hongxu Pan ◽  
Qian Xu ◽  
Jifeng Guo ◽  
...  

SNCA-rs11931074 had been demonstrated to be strongly correlated with PD risk. However, there was lack of comprehensive analysis of SNCA-rs11931074-related clinical features which may help explain clinical heterogeneity of PD. In our study, we performed association analyses on the relationship between SNCA-rs11931074 and motor symptoms, nonmotor symptoms, and comorbidities in PD. 611 rs11931074 carriers and 113 rs11931074 noncarriers were enrolled. In the clinical phenotype analyses, the Unified Parkinson’s Disease Rating Scale part II (UPDRS II) and part III (UPDRS III) scores of rs11931074 carriers were lower than those of noncarriers (SC: −0.083, p=0.035; SC: −0.140, p≤0.001). The Charlson Comorbidity Index (CCI) score of carriers was lower than that of noncarriers (SC: −0.097, p=0.009). No significant statistical differences were found between the variant and other clinical features such as motor complications and nonmotor symptoms. The SNCA-rs11931074 carriers may present with more benign clinical profiles than noncarriers with less severe motor symptoms and comorbidity burden.


2020 ◽  
Author(s):  
Valerie Joers ◽  
Gunasingh Masilamoni ◽  
Doty Kempf ◽  
Alison R Weiss ◽  
Travis Rotterman ◽  
...  

AbstractInflammation has been linked to the development of nonmotor symptoms in Parkinson’s disease (PD), which greatly impact patients’ quality of life and can often precede motor symptoms. Suitable animal models are critical for our understanding of the mechanisms underlying disease and the associated prodromal disturbances. The neurotoxin 1- methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkey model is commonly seen as a “gold standard” model that closely mimics the clinical motor symptoms and the nigrostriatal dopaminergic loss of PD, however MPTP toxicity extends to other nondopaminergic regions. Yet, there are limited reports monitoring the MPTP-induced progressive central and peripheral inflammation as well as other nonmotor symptoms such as gastrointestinal function and microbiota. The main objective of this study is to gain a broader understanding of central and peripheral inflammatory dysfunction triggered by exposure to a neurotoxicant known to degenerate nigral dopaminergic neurons in order to understand the potential role of inflammation in prodromal/pre-motor features of PD-like degeneration in a progressive non-human primate model of the disease. We measured inflammatory proteins in plasma and CSF and performed [18F]FEPPA PET scans to evaluate translocator proteins (TSPO) or microglial activation in a small cohort of rhesus monkeys (n=5) given weekly low doses of MPTP (0.2-0.8 mg/kg, im). Additionally, monkeys were evaluated for working memory and executive function using various behavior tasks and for gastrointestinal hyperpermeability and microbiota composition. Monkeys were also treated with novel TNF inhibitor XPro1595 (10mg/kg, n=3) or vehicle (n=2) every three days starting 11 weeks after the initiation of MPTP to determine whether nonmotor symptoms are tied to TNF signaling and whether XPro1595 would alter inflammation and microglial behavior in a progressive model of PD. Our analyses revealed sex-dependent sensitivity to MPTP that resulted in early microglial activation by PET, acute plasma IL-6 and CSF TNF, and earlier parkinsonism as measured by motor deficits in males compared to female monkeys. Sex differences were also identified in microbiota and their metabolites and targeted short chain fatty acids at both basal levels and in response to MPTP. Both sexes displayed cognitive impairment prior to a significant motor phenotype. Importantly, XPro1595 shifted peripheral and central inflammation, and significantly reduced CD68-immunoreactivity in the colon. As such, our findings revealed a sexually dimorphic inflammatory response to chronic MPTP treatment and suggest that males may have higher vulnerability than females to inflammation-induced degeneration. If these findings reflect potential differences in humans, these sex differences have significant implications for therapeutic development of inflammatory targets in the clinic.


2020 ◽  
Author(s):  
Monica R. Langley ◽  
Shivani Ghaisas ◽  
Bharathi N. Palanisamy ◽  
Muhammet Ay ◽  
Huajun Jin ◽  
...  

AbstractMitochondrial dysfunction has been implicated as a key player in the pathogenesis of Parkinson’s disease (PD). The MitoPark mouse, a transgenic mitochondrial impairment model developed by specific inactivation of TFAM in dopaminergic neurons, spontaneously exhibits progressive motor deficits and neurodegeneration, recapitulating several features of PD. Since non-motor symptoms are now recognized as important features of the prodromal stage of PD, we monitored the clinically relevant motor and nonmotor symptoms from ages 8-24 wks in MitoPark mice and their littermate controls. As expected, motor deficits in MitoPark mice began around 12-14 wks and became severe by 16-24 wks. Interestingly, male MitoPark mice showed spatial memory deficits before female mice, beginning at 8 wks and becoming most severe at 16 wks, as determined by Morris water maze. When compared to age-matched control mice, MitoPark mice exhibited olfactory deficits in novel and social scent tests as early as 10-12 wks. MitoPark mice between 16-24 wks spent more time immobile in forced swim and tail suspension tests, and made fewer entries into open arms of the elevated plus maze, indicating a depressive and anxiety-like phenotype, respectively. Importantly, depressive behavior as determined by immobility in forced swim test was reversible by antidepressant treatment with desipramine. Collectively, our results indicate that MitoPark mice progressively exhibit deficits in cognitive learning and memory, olfactory discrimination, and anxiety-and depression-like behaviors. Thus, MitoPark mice can serve as an invaluable model for studying motor and non-motor symptoms in addition to studying pathology in PD.


2021 ◽  
Vol 13 ◽  
Author(s):  
Xu-Ying Li ◽  
Wei Li ◽  
Xin Li ◽  
Xu-Ran Li ◽  
Linjuan Sun ◽  
...  

Serine 129-phosphorylated alpha-synuclein (pS-α-syn) is a major form of α-syn relevant to the pathogenesis of Parkinson's disease (PD), which has been recently detected in red blood cells (RBCs). However, alterations of RBC-derived pS-α-syn (pS-α-syn-RBC) in different subtypes and stages of PD remains to be investigated. In the present study, by using enzyme-linked immunosorbent assay (ELISA) to measure pS-α-syn-RBC, we demonstrated significantly higher levels of pS-α-syn-RBC in PD patients than in healthy controls. pS-α-syn-RBC separated the patients well from the controls, with a sensitivity of 93.39% (95% CI: 90.17–95.81%), a specificity of 93.11% (95% CI: 89.85–95.58%), and an area under the curve (AUC) of 0.96. Considering motor subtypes, the levels of pS-α-syn-RBC were significantly higher in late-onset than young-onset PD (p = 0.013) and in those with postural instability and gait difficulty than with tremor-dominant (TD) phenotype (p = 0.029). In addition, the levels of pS-α-syn-RBC were also different in non-motor subtypes, which were significantly lower in patients with cognitive impairment (p = 0.012) and olfactory loss (p = 0.004) than in those without such symptoms. Moreover, the levels of pS-α-syn-RBC in PD patients were positively correlated with disease duration and Hoehn &amp; Yahr stages (H&amp;Y) (p for trend =0.02 and &lt;0.001) as well as UPDRS III (R2 = 0.031, p = 0.0042) and MoCA scores (R2 = 0.048, p = 0.0004). The results obtained suggest that pS-α-syn-RBC can be used as a potential biomarker for not only separating PD patients from healthy controls but also predicting the subtypes and stages of PD.


2021 ◽  
Vol 11 ◽  
Author(s):  
Ditte Rudå ◽  
Gudmundur Einarsson ◽  
Anne Sofie Schott Andersen ◽  
Jannik Boll Matthiassen ◽  
Christoph U. Correll ◽  
...  

Background: Current assessments of motor symptoms in Parkinson's disease are often limited to clinical rating scales.Objectives: To develop a computer application using the Microsoft Kinect sensor to assess performance-related bradykinesia.Methods: The developed application (Motorgame) was tested in patients with Parkinson's disease and healthy controls. Participants were assessed with the Movement Disorder Society Unified Parkinson's disease Rating Scale (MDS-UPDRS) and standardized clinical side effect rating scales, i.e., UKU Side Effect Rating Scale and Simpson-Angus Scale. Additionally, tests of information processing (Symbol Coding Task) and motor speed (Token Motor Task), together with a questionnaire, were applied.Results: Thirty patients with Parkinson's disease and 33 healthy controls were assessed. In the patient group, there was a statistically significant (p &lt; 0.05) association between prolonged time of motor performance in the Motorgame and upper body rigidity and bradykinesia (MDS-UPDRS) with the strongest effects in the right hand (p &lt; 0.001). In the entire group, prolonged time of motor performance was significantly associated with higher Simson-Angus scale rigidity score and higher UKU hypokinesia scores (p &lt; 0.05). A shortened time of motor performance was significantly associated with higher scores on information processing (p &lt; 0.05). Time of motor performance was not significantly associated with Token Motor Task, duration of illness, or hours of daily physical activity. The Motorgame was well-accepted.Conclusions: In the present feasibility study the Motorgame was able to detect common motor symptoms in Parkinson's disease in a statistically significant and clinically meaningful way, making it applicable for further testing in larger samples.


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