Non-motor Manifestations Of Parkinson's Disease Research Articles

The use of the drug L-Carnitine Rompharm in patients with Parkinson's disease in the context of rational pharmacotherapy

The basic drug therapy for Parkinson's disease (PD) includes levodopa, dopamine receptor agonists (ADRs), type B monoamine oxidase enzyme inhibitors, catechol-O-methyltransferase inhibitors, and amantadine. In recent years, the efficacy of L-carnitine in neurodegenerative diseases and depression, which is often associated with PD, has been reported.
 Aim. To study the efficacy and safety of levocarnitine (L-Carnitine Rompharm) in PD patients of different ages and disease histories combined with ADR and levodopa.
 Materials and methods. A total of 142 patients with PD (aged 43 to 82 years) were followed-up from February 2020 to July 2022. All of these patients underwent clinical-neurological and neuropsychological examinations. In all patients, L-Carnitine Rompharm was used in the complex therapy of PD in combination with ADR and levodopa. Therapy efficacy was assessed using the International Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS UPDRS).
 Results. After the course of therapy, significant (p0.05) improvements in non-motor manifestations of PD (MDS UPDRS scale I), motor manifestations of PD (MDS UPDRS scale II), and motor function indices (MDS UPDRS scale III) were observed in all age groups. Improvements in hypokinesia, rigidity, motor fluctuations (depletion of levodopa effect), peak dose dyskinesia, and postural instability were observed; thought processes, behavior, mood, and daily life activity were also improved. L-carnitine showed good tolerability and absence of side effects.
 Conclusion. The efficacy and safety of L-Carnitine Rompharm in PD patients of different ages have been demonstrated.

White matter hyperintensity presence, quantity, and location exhibits no association with motor and non-motor manifestations of PD

IntroductionNonspecific areas of brain white matter hyperintensity (WMH) are commonly found in the elderly. Some studies have shown that the presence, quantity, and location of WMHs may be associated with the development of cognitive and motor decline in patients with Parkinson's disease (PD), but the results remain controversial. This study aimed to evaluate the relationship of WMH to motor and non-motor symptoms, including dysautonomia and rapid eye movement sleep behavior disorder (RBD), in patients with PD. MethodsBrain magnetic resonance images were acquired from 120 patients diagnosed with PD and analyzed for WMH classification and quantification. Motor symptoms were quantified using sub-scores of the Movement Disorder Society-Unified Parkinson Disease Rating Scale (MDS-UPDRS)-III. Dysautonomia was evaluated by autonomic reactivity tests, and polysomnography was used for the diagnosis of RBD. ResultsAge, total value of the MDS-UPDRS-III tremor sub-score, and the presence of dysautonomia were found to be linearly positively associated. Specifically, the duration of PD was positively associated with rigidity, bradykinesia, axial symptoms, prevalence of dysautonomia, and RBD sub-scores. However, in the multivariate analysis adjusted for variables of interest, no statistical significance was found for any of the models. ConclusionThe presence, quantity, and location of WMH were not associated with the analyzed motor and non-motor manifestations of PD.

The role of frailty in Parkinson's disease: a cross-sectional study.

Frailty is an age-related state of increased risk for health-related adverse outcomes that reflects multisystem physiological changes and likely influences the clinical expression and disease progression of neurodegenerative disorders. The aim of the present study was to assess the potential relationship between frailty, as assessed by a frailty index (FI), and motor symptom severity, motor subtypes, and non-motor domains in Parkinson's disease (PD). We consecutively enrolled 150 PD patients. We administered an FI specifically designed for PD that included 50 age-related multidimensional biological deficits. Patients underwent a clinical assessment that evaluated motor and non-motor manifestations of PD. Using the FI score, we classified PD patients as relatively fit (FI ≤ 0.10), less fit (0.10 < FI ≤ 0.21), or frail (FI > 0.21). A linear regression model was designed to explore possible associations between frailty level and PD motor and non-motor manifestations. Frail patients showed greater motor symptom severity and motor complications than fitter patients. A trend towards a higher prevalence of the postural instability/gait disorder subtype was also observed in frail versus relatively fit and less fit patients. The global burden of non-motor symptoms was higher in frail patients. Increased frailty was associated with more severe motor and non-motor symptoms, as well as with more pronounced cognitive deficits. These associations remained significant even when "traditional" predictors of PD severity (age, disease duration, and levodopa equivalent daily dose) were considered. The present findings indicate that the FI is associated with both motor and non-motor features of PD.

COGNITIVE DISORDERS IN PATIENTS WITH PARKINSON'S DISEASE ON THE BACKGROUND OF AUTOIMMUNE PATHOLOGY

Parkinson's disease (PD) is a progressive neurodegenerative disease characterized by the predominantly dopaminergic neuronal black matter degeneration. The multicentre study of PRIAMO (PaRkinson &amp; non Motor symptom) showed that in 98.6 % of cases, non-motor symptoms (NMS) were observed in patients with PD. Cognitive impairment is one of the most common NMS PD. According to these studies, cognitive dysfunction develops in most patients at an early stage of the disease, with mild to moderate cognitive impairment. In the later stages of the disease, dementia occurs in 80 % of patients with PD. Aim of the research. To study the peculiarities of cognitive impairment in patients with PD and autoimmune thyroiditis (AIT), their association with motor and non-motor disorders, and to assess the impact on the quality of life of patients. Materials and methods of the research. 109 patients with PD aged 47 to 75 years were examined. The main group consisted of patients with IA and IB subgroups, control – IIA and IIB subgroups. General clinical and neurological examinations, evaluation of motor functions by the Unified Parkinson's disease Rating Scale (UPDRS), neuropsychological testing (MMSE, MoCA, FAB, BDI), Hamilton's Alert Scale (HARS), scale used for assessing autonomic disorders in patients with PD and Parkinson’s disease questionnaire (PDQ-39), statistical analysis using the "Statistica 6.0" program. Results. Neuropsychological testing showed that MMSE, MoCA, and FAB obtained from patients with PD and AIT are lower compared to patients with PD. Analyzing the indicators of MMSE, FAB, and MoCA scales in dynamics, a statistically significant difference was found in subgroups of IB and IIB; in subgroups of IA and IIA – was not observed. During the analysis of the results of the neuropsychological testing, no association was found at the statistically significant level in the subgroups of IA and IB between the duration of the disease and MMSE, MoCA, and FAB scales. In the IA subgroup, in the initial review, feedback was observed on a statistically significant level of average strength between the level of anxiety and the indicator of the MMSE scale, an indicator of the MoCA scale. In the IA subgroup, there was no relationship at the statistically significant level between the indicators of neuropsychological testing (MMSE, MoCA, FAB) and motor and non-motor manifestations (depression, vegetative disorders). There was a connection at a statistically significant level between the indicators of neuropsychological testing (MMSE, MoCA, FAB) and motor and non-motor manifestations of PD in patients who received anti-parkinsonian therapy for a long period of time. The negative influence of the level of cognitive impairments on the quality of life of patients with PD and AIT was revealed, indicating the high medical and social significance of these violations. Conclusions. Neuropsychological testing showed that MMSE, MoCA, FAB scores in patients with PD and AIT (IB subgroup) were lower compared to patients with PD (IIB subgroup). There was a connection at a statistically significant level between the indicators of neuropsychological testing (MMSE, MoCA, FAB) and motor and non-motor manifestations of PD in patients who received anti-parkinsonian therapy for a long period of time. The negative influence of the level of cognitive impairments on the quality of life of patients with PD and AIT was revealed, indicating the high medical and social significance of these violations.

Comparative characteristics of non-motor manifestations of Parkinson disease in men and women

Comparative characteristics of non-motor manifestations of Parkinson disease in men and women

Evaluation of orthostatic hypotension in Parkinson disease by measuring the catecholamine level and using a Cardiac MIBG scintigraphy

Background: Orthostatic hypotension (OH) is one of the non-motor manifestations of Parkinson disease (PD), however the responsible lesion of OH in PD is still unclear.

Serotonergic Approaches in Parkinson's Disease: Translational Perspectives, an Update.

Parkinson's disease (PD) has long been seen as a disorder caused by degeneration of the dopaminergic system, leading to the classic motor manifestations of the disease. However, there is now overwhelming evidence that PD is more than a disease merely caused by dopamine depletion. It is well-known that a myriad of other neurotransmitters are affected by the disease process. One such neurotransmitter is serotonin (5-HT). 5-HT has been shown to play a role in several motor and nonmotor manifestations of PD, including tremor, cognition, depression and psychosis. 5-HT also seems to play a critical role in L-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesia. A breadth of preclinical studies and clinical trials have been conducted that aimed at modulating the 5-HT system in order to alleviate depression, cognitive deficits, psychosis, and dyskinesia. In this Review, we summarize recent advances in the 5-HT field in PD, but with a translational emphasis. We start by presenting a novel nonhuman primate model of PD that presents with dual dopamine and 5-HT lesions. We then present preclinical and clinical data that introduce new concepts, such as the use of biased and partial agonists, as well as molecules recently introduced to the field of PD, such as eltoprazine, pimavanserin, nelotanserin, and SYN-120, to enhance therapeutic benefit while minimizing adverse events, notably on parkinsonian disability.

Timed Light Therapy for Sleep and Daytime Sleepiness Associated With Parkinson Disease

Impaired sleep and alertness are some of the most common nonmotor manifestations of Parkinson disease (PD) and currently have only limited treatment options. Light therapy (LT), a widely available treatment modality in sleep medicine, has not been systematically studied in the PD population. To determine the safety and efficacy of LT on excessive daytime sleepiness (EDS) associated with PD. This randomized, placebo-controlled, clinical intervention study was set in PD centers at Northwestern University and Rush University. Participants were 31 patients with PD receiving stable dopaminergic therapy with coexistent EDS, as assessed by an Epworth Sleepiness Scale score of 12 or greater, and without cognitive impairment or primary sleep disorder. Participants were randomized 1:1 to receive bright LT or dim-red LT (controlled condition) twice daily in 1-hour intervals for 14 days. This trial was conducted between March 1, 2007, and October 31, 2012. Data analysis of the intention-to-treat population was conducted from November 1, 2012, through April 30, 2016. The primary outcome measure was the change in the Epworth Sleepiness Scale score comparing the bright LT with the dim-red LT. Secondary outcome measures included the Pittsburgh Sleep Quality Index score, the Parkinson's Disease Sleep Scale score, the visual analog scale score for daytime sleepiness, and sleep log-derived and actigraphy-derived metrics. Among the 31 patients (13 males and 18 females; mean [SD] disease duration, 5.9 [3.6] years), bright LT resulted in significant improvements in EDS, as assessed by the Epworth Sleepiness Scale score (mean [SD], 15.81 [3.10] at baseline vs 11.19 [3.31] after the intervention). Both bright LT and dim-red LT were associated with improvements in sleep quality as captured by mean (SD) scores on the Pittsburg Sleep Quality Index (7.88 [4.11] at baseline vs 6.25 [4.27] after bright LT, and 8.87 [2.83] at baseline vs 7.33 [3.52] after dim-red LT) and the Parkinson's Disease Sleep Scale (97.24 [22.49] at baseline vs 106.98 [19.37] after bright LT, and 95.11 [19.86] at baseline vs 99.28 [16.94] after dim-red LT). Bright LT improved several self-reported mean (SD) sleep metrics, including sleep fragmentation (number of overnight awakenings, 1.51 [1.03] at baseline vs 0.92 [0.97] after the intervention), sleep quality (sleep diary score, 3.03 [1.01] at baseline vs 3.53 [0.91] after the intervention), and ease of falling asleep (sleep diary score, 2.32 [0.89] at baseline vs 1.83 [0.88] after the intervention). Light therapy was associated with increased daily physical activity as assessed by actigraphy (average activity [SD] counts, 165.01 [66.87] at baseline vs 194.59 [87.81] after the intervention). Light therapy was well tolerated and may be a feasible intervention for improving the sleep-wake cycles in patients with PD. Further studies are required to determine optimal parameters of LT for PD. clinicaltrials.gov Identifier: NCT01338649.

The Impact of Levodopa on Quality of Life in Patients With Parkinson Disease

Parkinson disease (PD) is associated with a progressive decline in patient quality of life (QoL), because of motor and nonmotor manifestations of PD and treatment-related side effects. Treatment with carbidopa/levodopa-the current gold standard therapy-improves QoL in the short term, but gains are not maintained over a long term. Long-term treatment is associated with symptom re-emergence (end-of-dose "wearing off") and development of dyskinesia, which may have an adverse impact on QoL. Levodopa (LD; combined with carbidopa) remains the gold standard for symptomatic treatment of PD, but long-term treatment is associated with complications that may adversely affect QoL. Recent studies have suggested that the addition of a catechol-O-methyltransferase inhibitor may improve QoL through the reduction of some of the motor complications of LD therapy. Further studies are required to determine the full effects of this as well as other treatments that are used to manage LD-associated complications on QoL.

Association of anosmia with autonomic failure in Parkinson disease

Olfactory dysfunction and autonomic failure are gaining recognition as nonmotor manifestations of Parkinson disease (PD). This observational study assessed whether in PD anosmia and autonomic failure are related to each other or to neuroimaging evidence of striatal dopamine deficiency. Olfactory function was assessed by the University of Pennsylvania Smell Identification Test (UPSIT) in 23 patients with sporadic PD. Baroreflex-cardiovagal gain was quantified from the relationship between cardiac interbeat interval and systolic pressure during the Valsalva maneuver and baroreflex-sympathoneural function by responses of systolic pressure to the Valsalva maneuver and of hemodynamics and plasma norepinephrine (NE) and dihydroxyphenylglycol (DHPG) levels to orthostasis. 6-[(18)F]Fluorodopamine PET and plasma and skeletal muscle microdialysate NE and DHPG were used to indicate cardiac and extracardiac noradrenergic innervation and brain 6-[(18)F]fluorodopa PET to indicate striatal dopaminergic innervation. Parkinsonism was assessed by UPDRS scores. Compared to patients with PD and normal to moderately decreased sense of smell, patients with anosmic PD had lower mean baroreflex-cardiovagal gain (p = 0.04), larger falls in systolic pressure during the Valsalva maneuver and orthostasis (p = 0.04, p = 0.02), smaller orthostatic increments in plasma NE and DHPG (p = 0.003, p = 0.03), lower cardiac septal:hepatic and renal cortical:hepatic ratios of 6-[(18)F]fluorodopamine-derived radioactivity (p = 0.01, p = 0.06), and lower microdialysate NE and DHPG (p = 0.01; p = 0.006). Neither clinical severity of parkinsonism nor the putamen:occipital cortex ratio of 6-[(18)F]fluorodopa-derived radioactivity was related to the UPSIT category. In Parkinson disease, anosmia is associated with baroreflex failure and cardiac and organ-selective extracardiac noradrenergic denervation, independently of parkinsonism or striatal dopaminergic denervation.

Neuropathology of non-motor features of Parkinson disease

Non-motor manifestations of Parkinson disease (PD) are common and some may actually antedate motor dysfunction. Extrapyramidal signs in PD are tightly linked to striatonigral dopaminergic denervation associated with neuronal loss and Lewy bodies in the residual neurons of the substantia nigra. Lewy bodies composed of abnormal alpha-synuclein are the histologic hallmark of PD, and their presence beyond midbrain dopaminergic neurons is considered to be the pathologic substrate of many, if not all, of the non-motor manifestations of PD. We review the pathologic correlates of autonomic dysfunction (cardiac and gastrointestinal), hyposmia, depression, rapid eye movement behavior disorder and dementia in PD For each non-motor clinical feature there is strong evidence to suggest a role for alpha-synuclein pathology, lending further support for the notion that PD is a multisystem alpha-synucleinopathy.

Manifestations of Parkinson disease differ in association with REM sleep behavior disorder

REM sleep behavior disorder (RBD) is commonly associated with Parkinson disease (PD), but it is unclear whether this association has implications for disease manifestations. We evaluated 36 PD patients for the presence of RBD by polysomnography. Patients underwent an extensive evaluation by a movement disorders specialist blinded to polysomnography results. Severity of motor manifestations, autonomic, visual, psychiatric, and olfactory dysfunctions and quality of life (QOL) were assessed, and compared using regression analysis that adjusted for disease duration, age and sex. Severity of motor manifestations did not differ between groups. However, the presence of RBD in PD was strongly associated with symptoms and signs of orthostatic hypotension (systolic blood pressure lying to standing = -25.7 +/- 13.0 mmHg vs. -4.9 +/-14.1, P < 0.001); and orthostatic symptom prevalence = 71% vs. 27%, P = 0.0076). There was no association between RBD and other autonomic symptoms. Color vision was worse in patients with RBD, but olfactory dysfunction did not differ between groups. The prevalence of depression, hallucinations, paranoia, and impulse disorders did not differ between groups. Emotional functioning and general health QOL measures were lower in those with RBD, but there were no differences between groups on disease-specific indices or on measures of overall physical QOL. These findings suggest that the pathophysiology of RBD and nonmotor manifestations of PD, particularly autonomic dysfunction, are linked.

Neural control of the gastrointestinal tract: Implications for Parkinson disease

Disorders of swallowing and gastrointestinal motility are prominent nonmotor manifestations of Parkinson disease (PD). Motility of the gut is controlled both by extrinsic inputs from the dorsal motor nucleus of the vagus (DMV) and paravertebral sympathetic ganglia and by local reflexes mediated by intrinsic neurons of the enteric nervous system (ENS). Both the ENS and the DMV are affected by Lewy body pathology at early stages of PD. This early involvement provides insights into the pathophysiology of gastrointestinal dysmotility in this disorder and may constitute an important step in the etiopathogenesis of Lewy body disease.

Clinical correlates of action tremor in Parkinson disease.

Action tremor is often noted in patients with Parkinson disease (PD), yet the clinical correlates of this type of tremor have been the focus of few studies. It is not clear whether this action tremor is a manifestation of the underlying basal ganglia disease. To determine whether the severity of action tremor in PD is associated with age, age at disease onset, disease duration, levodopa dose, severity of rest tremor, or other motor (ie, bradykinesia, rigidity) and nonmotor manifestations of PD. Patients with PD (N = 197) were ascertained as part of a familial aggregation study. All patients underwent a neurological examination. Rest tremor was rated with the Unified Parkinson Disease Rating Scale; and action tremor, with the Washington Heights-Inwood Genetic Study of Essential Tremor Rating Scale. Action tremor was present in 184 (93.4%) of 197 patients. Four patients (2%) met criteria for definite essential tremor. The action tremor score was not associated with age, age at onset, or disease duration. The action tremor score was associated with the rest tremor score (r = 0.37; P<.001), and more strongly with the ipsilateral than contralateral rest tremor score. The association between the action tremor score and the rest tremor score was diminished but still significant (r = 0.21, P<.02) even when we excluded these 63 patients with re-emergent tremor. Neither the action nor the rest tremor score was associated with the bradykinesia or rigidity scores, Hoehn and Yahr scale score, or modified Mini-Mental State Examination score. Action tremor was associated with rest tremor in PD, suggesting that, at least in part, action tremor is a manifestation of the underlying basal ganglia disease. Neither tremor was associated with other motor and nonmotor manifestations of PD. This in turn suggests that tremor in PD may represent an underlying pathophysiological process different from these other manifestations.