Mood disturbances and cognitive functioning in Parkinson's disease: The effects of disease duration and side of onset of motor symptoms

Abstract There is an increasing recognition of the significant non-motor symptoms that burden people with Parkinson’s disease. As such, there is a pressing need to better understand and investigate the mechanisms underpinning these non-motor deficits. The electrical activity within the brains of people with Parkinson’s disease is known to exhibit excessive power within the beta range (12–30 Hz), compared with healthy controls. The weight of evidence suggests that this abnormally high level of beta power is the cause of bradykinesia and rigidity in Parkinson’s disease. However, less is known about how the abnormal beta rhythms seen in Parkinson’s disease impact on non-motor symptoms. In healthy adults, beta power decreases are necessary for successful episodic memory formation, with greater power decreases during the encoding phase predicting which words will subsequently be remembered. Given the raised levels of beta activity in people with Parkinson’s disease, we hypothesized that the necessary decrease in power during memory encoding would be diminished and that this would interfere with episodic memory formation. Accordingly, we conducted a cross-sectional, laboratory-based experimental study to investigate whether there was a direct relationship between decreased beta modulation and memory formation in Parkinson’s disease. Electroencephalography recordings were made during an established memory-encoding paradigm to examine brain activity in a cohort of adults with Parkinson’s disease (N = 28, 20 males) and age-matched controls (N = 31, 18 males). The participants with Parkinson’s disease were aged 65 ± 6 years, with an average disease duration of 6 ± 4 years, and tested on their normal medications to avoid the confound of exacerbated motor symptoms. Parkinson’s disease participants showed impaired memory strength (P = 0.023) and reduced beta power decreases (P = 0.014) relative to controls. Longer disease duration was correlated with a larger reduction in beta modulation during encoding, and a concomitant reduction in memory performance. The inability to sufficiently decrease beta activity during semantic processing makes it a likely candidate to be the central neural mechanism underlying this type of memory deficit in Parkinson’s disease. These novel results extend the notion that pathological beta activity is causally implicated in the motor and (lesser appreciated) non-motor deficits inherent to Parkinson’s disease. These findings provide important empirical evidence that should be considered in the development of intelligent next-generation therapies.

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Neurocognitive Correlates of Apathy and Anxiety in Parkinson's Disease

Parkinson s Disease ◽

10.1155/2012/793076 ◽

2012 ◽

Vol 2012 ◽

pp. 1-9 ◽

Cited By ~ 9

Author(s):

Yelena Bogdanova ◽

Alice Cronin-Golomb

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Neuropsychological Tests ◽

Rating Scales ◽

Disease Duration ◽

Differential Association ◽

Motor Symptoms ◽

Healthy Controls ◽

Nonmotor Symptoms ◽

Neurocognitive Profiles

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.

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Quality of Life in Newly Diagnosed Patients With Parkin-Related Parkinson's Disease

Frontiers in Neurology ◽

10.3389/fneur.2020.580910 ◽

2020 ◽

Vol 11 ◽

Author(s):

Xin-Yue Zhou ◽

Feng-Tao Liu ◽

Chen Chen ◽

Su-Shan Luo ◽

Jue Zhao ◽

...

Keyword(s):

Quality Of Life ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Excessive Daytime Sleepiness ◽

Daytime Sleepiness ◽

Disease Duration ◽

Motor Symptoms ◽

Newly Diagnosed ◽

Non Motor Symptoms

Introduction: Mutations in the Parkin gene are the most common cause of autosomal recessive early-onset Parkinson's disease (PD). However, little is known about the quality of life (QoL) in Parkin-related PD. Here, we investigated the patterns of QoL in newly diagnosed Parkin-related PD patients.Methods: Newly diagnosed PD patients (diagnosis made within 12 months) who had an age of onset (AOO) below 40 and underwent a PD-related genetic testing, were recruited (n = 148). Among them, 24 patients carried bi-allelic variants in Parkin (PD-Parkin) and 24 patients did not have any known causative PD mutations, or risk variants (GU-EOPD). The clinical materials, relevant factors and determinants of QoL were analyzed.Results: PD-Parkin patients had a younger AOO (p = 0.003) and longer disease duration (p = 0.005). After adjustment for AOO and disease duration, more dystonia (p = 0.034), and worse scores of non-motor symptoms including Beck depression inventory (BDI, p = 0.035), Epworth sleepiness scale (ESS, p = 0.044), and subdomains of depression/anxiety (p = 0.015) and sleep disorders (p = 0.005) in Non-motor symptoms questionnaire, were found in PD-Parkin comparing with GU-EOPD. PD-Parkin patients had poorer QoL (adjusted p = 0.045), especially in the mobility (adjusted p = 0.025), emotional well-being (adjusted p = 0.015) and bodily discomfort dimensions (adjusted p = 0.016). BDI scores (p = 0.005) and ESS scores (p = 0.047) were significant determinants of QoL in PD-Parkin.Conclusion: Newly diagnosed PD-Parkin patients showed worse QoL. More depression and excessive daytime sleepiness predicted worse QoL. For clinicians, management of depression and excessive daytime sleepiness is suggested to better improve QoL in patients with Parkin mutations.

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The severity progression of non-motor symptoms in Parkinson’s disease: a 6-year longitudinal study in Taiwanese patients

Scientific Reports ◽

10.1038/s41598-021-94255-9 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yi-Chieh Chen ◽

Rou-Shayn Chen ◽

Yi-Hsin Weng ◽

Ying-Zu Huang ◽

Chiung Chu Chen ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Longitudinal Study ◽

Disease Duration ◽

Rating Scale ◽

Medical Center ◽

Motor Symptoms ◽

Disease Rating ◽

Non Motor Symptoms

AbstractNonmotor symptoms (NMSs) cause major burden in patients with Parkinson’s disease (PD). Previous NMSs progression studies mostly focused on the prevalence. We conducted a longitudinal study to identify the progression pattern by the severity. PD patients recruited from the outpatient clinics of a tertiary medical center were evaluated by the Unified Parkinson's Disease Rating Scale and Non-Motor Symptoms Scale (NMSS). A retrospective study with three-step analysis was performed. Step 1, the NMSs severity was compared among patients stratified by disease duration every 2 years up to 10 years. Step 2, patients with repeated tests in 2 years were categorized into 4 groups by the diseased duration of every 5 years. Step 3, the NMSS score changes in 6 years follow-up were determined, and the dosage of anti-PD drugs was compared to the NMSs severity changes. 676 patients completed the step 1 analysis, which showed a trend of NMSs worsening but not significant until the disease duration longer than 4–6 years. Furthermore, the severity did not change between repeated evaluations in 2 years in all patients. The progression became apparent after 6 years. Individual symptoms had different progression patterns and the increment of medications was independent to NMSs evolution. We demonstrated the NMSs severity progression in Taiwanese PD patients and the independence of the medications and NMSs progression.

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People with Parkinson’s Disease: What Symptoms Do They Most Want to Improve and How Does This Change with Disease Duration?

Journal of Parkinson s Disease ◽

10.3233/jpd-202346 ◽

2021 ◽

pp. 1-10

Author(s):

Rebecca J. Port ◽

Martin Rumsby ◽

Graham Brown ◽

Ian F. Harrison ◽

Anneesa Amjad ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Psychological Health ◽

Online Survey ◽

Disease Duration ◽

Future Research ◽

Free Text ◽

Motor Symptoms ◽

Walking Balance ◽

Non Motor Symptoms

Background: Parkinson’s disease (PD) is a neurodegenerative condition with a diverse and complex pattern of motor and non-motor symptoms which change over time with disease duration. Objective: The aims of the present study were to discover what symptoms matter most to people with the condition and to examine how these priorities change with disease duration. Methods: A simple free-text online survey (using SmartSurvey) was developed by Parkinson’s UK, which asked participants to identify up to three aspects of the condition they would most like to see improvement in. Results: 790 people participated reporting 2,295 issues related to PD which were grouped into 24 broad symptom domains. Of these, 1,358 (59.1%) were categorised as motor symptoms, 859 (37.4%) as non-motor issues and 78 (3.4%) as medication problems. This study reveals how certain features of PD become more or less important to patients as the condition progresses. Non-motor symptoms were highly cited from the very earliest stages of PD. Problems with walking, balance and falls, speech problems, freezing and dyskinesia become increasingly important as the condition progresses whereas tremor, stiffness and psychological health become decreasingly important as the condition progresses. Conclusions: The data suggest that the priorities of people affected by PD for improving life are personal and change with duration of the condition. These findings have implications for developing person-centred management and care, as well as for directing future research to improve quality of life.

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Clinical factors affecting evoked magnetic fields in patients with Parkinson’s disease

10.1101/2020.04.23.057679 ◽

2020 ◽

Author(s):

Ryoji Naganuma ◽

Ichiro Yabe ◽

Megumi Takeuchi ◽

Kirari Morishita ◽

Shingo Nakane ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Magnetic Fields ◽

Cognitive Functioning ◽

Cognitive Functions ◽

Clinical Characteristics ◽

Motor Symptoms ◽

Cognitive Tests ◽

Evoked Responses ◽

Evoked Fields

AbstractStudies 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.

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Self-Reported Symptoms of Parkinson’s Disease by Sex and Disease Duration

Western Journal of Nursing Research ◽

10.1177/0193945916670904 ◽

2016 ◽

Vol 39 (11) ◽

pp. 1412-1428 ◽

Cited By ~ 3

Author(s):

Ju Young Shin ◽

Ryan T. Pohlig ◽

Barbara Habermann

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Disease Duration ◽

Community Dwelling ◽

Motor Symptoms ◽

Cross Sectional ◽

Wide Range ◽

Future Care ◽

Descriptive Survey ◽

Non Motor Symptoms

Parkinson’s disease (PD) is a neurodegenerative disease with a wide range of symptom presentations. The purpose of this research was to compare self-reported motor and non-motor symptoms of PD by sex and disease duration. This study was a cross-sectional descriptive survey in community-dwelling people with PD. A total of 141 participants (64.6% response rate; 59.6% men; Mage = 69.7 years) were included. Males reported more rigidity, speech problems, sexual dysfunction, memory problems, and socializing problems than females. The number of motor symptoms in three groups divided by increments of 5 years was significantly increased. Postural instability, freezing, off periods, dyskinesia, speech problems, and hallucinations/psychosis were significantly increased as the disease duration increased. Thorough assessment of motor and non-motor symptoms could decrease the risk of inadequate symptom management. Provision of information regarding PD symptoms at each stage may help people with PD and their caregivers in planning their future care and life.

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Disease duration-related differences in non-motor symptoms: A study of 616 Chinese Parkinson's disease patients

Journal of the Neurological Sciences ◽

10.1016/j.jns.2013.03.022 ◽

2013 ◽

Vol 330 (1-2) ◽

pp. 32-37 ◽

Cited By ~ 15

Author(s):

Xiaoyan Guo ◽

Wei Song ◽

Ke Chen ◽

XuePing Chen ◽

Zhenzhen Zheng ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Disease Duration ◽

Motor Symptoms ◽

Non Motor Symptoms

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Natural history of motor symptoms in Parkinson’s disease and the long-duration response to levodopa

Brain ◽

10.1093/brain/awaa181 ◽

2020 ◽

Vol 143 (8) ◽

pp. 2490-2501 ◽

Cited By ~ 2

Author(s):

Roberto Cilia ◽

Emanuele Cereda ◽

Albert Akpalu ◽

Fred Stephen Sarfo ◽

Momodou Cham ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Disease Duration ◽

Rating Scale ◽

Natural Course ◽

Sub Saharan Africa ◽

Motor Symptoms ◽

Motor Disability ◽

Long Duration

Abstract The natural pattern of progression of Parkinson’s disease is largely unknown because patients are conventionally followed on treatment. As Parkinson’s disease progresses, the true magnitude of the long-duration response to levodopa remains unknown, because it can only be estimated indirectly in treated patients. We aimed to describe the natural course of motor symptoms by assessing the natural OFF in consecutive Parkinson’s disease patients never exposed to treatment (drug-naïve), and to investigate the effects of daily levodopa on the progression of motor disability in the OFF medication state over a 2-year period. In this prospective naturalistic study in sub-Saharan Africa, 30 Parkinson’s disease patients (age at onset 58 ± 14 years, disease duration 7 ± 4 years) began levodopa monotherapy and were prospectively assessed using the Unified Parkinson’s disease Rating Scale (UPDRS). Data were collected at baseline, at 1-year and 2-years follow-up. First-ever levodopa intake induced a significant improvement in motor symptoms (natural OFF versus ON state UPDRS-III 41.9 ± 15.9 versus 26.8 ± 15.1, respectively; P < 0.001). At 1-year follow-up, OFF state UPDRS-III score after overnight withdrawal of levodopa was considerably lower than natural OFF (26.5 ± 14.9; P < 0 .001). This effect was not modified by disease duration. At the 2-year follow-up, motor signs after overnight OFF (30.2 ± 14.2) were still 30% milder than natural OFF (P = 0.001). The ON state UPDRS-III at the first-ever levodopa challenge was similar to the overnight OFF score at 1-year follow-up and the two conditions were correlated (r = 0.72, P < 0.001). Compared to the natural progression of motor disability, levodopa treatment resulted in a 31% lower annual decline in UPDRS-III scores in the OFF state (3.33 versus 2.30 points/year) with a lower model’s variance explained by disease duration (67% versus 36%). Using the equation regressed on pretreatment data, we predicted the natural OFF at 1-year and 2-year follow-up visits and estimated that the magnitude of the long-duration response to levodopa ranged between 60% and 65% of total motor benefit provided by levodopa, independently of disease duration (P = 0.13). Although levodopa therapy was associated with motor fluctuations, overnight OFF disability during levodopa was invariably less severe than the natural course of the disease, independently of disease duration. The same applies to the yearly decline in UPDRS-III scores in the OFF state. Further research is needed to clarify the mechanisms underlying the long-duration response to levodopa in Parkinson’s disease. Understanding the natural course of Parkinson’s disease and the long-duration response to levodopa may help to develop therapeutic strategies increasing its magnitude to improve patient quality of life and to better interpret the outcome of randomized clinical trials on disease-modifying therapies that still rely on the overnight OFF to define Parkinson’s disease progression.

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