Olfactory dysfunction and cardiovascular dysautonomia in Parkinson’s disease

Several studies have reported that olfactory dysfunction is an early neuropathological manifestation of Parkinson’s disease (PD). Reduced cardiac meta-iodobenzylguanidine (¹²³I-MIBG) uptake may be one of the earliest signs of PD. We studied the relation of olfactory dysfunction to cardiovascular dysautonomia in patients with PD. The study group comprised 66 patients with PD (70.5 years) and 26 controls (70.3 years) for olfactory assessment, 21 controls (72.1 years) for cardiac ¹²³I-MIBG scintigraphy and heart rate variability (HRV), assessed using the coefficient of variation for RR intervals (HRV), and 23 controls (69.2 years) for orthostatic blood pressure response. Olfactory function was assessed by the odor stick identification test Japan (OSIT-J), and cardiovascular autonomic function was evaluated by ¹²³I-MIBG scintigraphy of the heart, the fall in orthostatic blood pressure, and HRV. Patients with PD had a significantly lower OSIT-J score than did the controls (4.1 ± 3.0 vs. 9.9 ± 1.7, p = 0.001). The OSIT-J score was unrelated to variables other than gender, including age, disease duration, motor score on the unified Parkinson’s disease rating scale, score on the mini-mental state examination, motor phenotype, visual hallucinations, and dopaminergic medication on multiple regression and logistic regression analyses. The OSIT-J score was related to the heart/mediastinum ratio of cardiac ¹²³I-MIBG uptake, the fall in orthostatic blood pressure, and HRV, after adjustment for other clinical variables. Olfactory dysfunction in PD was, thus, significantly related to both cardiac sympathetic and parasympathetic dysfunction, as well as vascular sympathetic dysfunction. As non-motor symptoms of PD, olfactory dysfunction and autonomic network failure appear to be closely related in PD.     

Olfactory dysfunction and parasympathetic dysautonomia in Parkinson’s disease

Objective

Olfactory impairment occurs early in Parkinson’s disease (PD), as may dysautonomia. We investigated the relationship between olfaction and dysautonomia as well as other non-motor manifestations of PD.

Methods

Olfaction [University of Pennsylvania Smell Identification Test (UPSIT)], autonomic function in the pupillary (constriction and redilation velocity) and cardiac systems (resting low- and high-frequency heart rate variability (LF and HF HRV), positional changes in systolic blood pressure), neuropsychiatric function [Mini-mental Status Exam (MMSE)], Hamilton Depression Scale, activities of daily living [(ADLs), Schwab and England ADLs scale], quality of life [Short Form-36 health survey, PD Questionnaire 39 (PDQ-39)], and other non-motor symptoms [Non-motor Symptoms Scale (NMSS)] were simultaneously assessed in 33 participants (15 PD, 18 controls). Group comparisons, Spearman’s coefficients and non-parametric rank-based regression were employed to characterize relationships between olfaction and non-motor features.

Results

Smell scores were lower in the PD group and correlated positively with pupil constriction velocity and HF HRV. Smell scores were correlated negatively with PDQ-39 and gastrointestinal items of the NMSS and positively with MMSE and Schwab and England ADLs. These correlated measures were not significant terms in regression models of smell scores in which age and PD diagnosis were significant and accounted for over half of the variability (R-squared 0.52–0.58).

Interpretation

This study suggests olfactory involvement occurs with parasympathetic dysautonomia in the pupillary and cardiovascular systems, involving both age-related and PD-related processes. Other non-motor features are concurrently involved, supporting the notion that aging and PD have widespread effects involving discrete portions of the autonomic and olfactory systems.     

Precision medicine in Parkinson’s disease: emerging treatments for genetic Parkinson’s disease

Journal of Neurology - In recent years, numerous clinical trials for disease modification in Parkinson’s disease (PD) have failed, possibly because of a “one-size-fits all”...     

Validation of diagnostic criteria for apathy in Parkinson’s disease

BackgroundApathy is a common neuropsychiatric syndrome in Parkinson’s Disease (PD) that affects quality of life. Research into apathy has been hampered by a lack of broadly accepted diagnostic criteria. Recently, diagnostic criteria for apathy in neuropsychiatric disorders have been proposed, which to date have not been validated in PD.AimTo validate the proposed diagnostic criteria for apathy in PD.Design and methodsIn a cross-sectional study, outpatients with PD visiting a movement disorders clinic underwent a protocolized assessment of motor function, activities of daily living (ADL), cognition and mood. In addition, the diagnostic criteria for apathy were administered as well as two apathy rating instruments: the Lille Apathy Rating Scale (LARS) and the apathy section of the Neuropsychiatric Inventory (NPI).ResultsOf the included patients 17.2% were diagnosed with apathy according to the criteria. Acceptability and internal consistency of the criteria was good, as was the concurrent validity with the LARS and apathy section of the NPI. Discriminant validity of the criteria with depression was moderate to good. All domains of criterion B (behavior, cognition, emotion) contributed to the diagnosis of apathy, of which reduced goal-directed behavior was the most frequently observed symptom.ConclusionThe recently proposed diagnostic criteria for apathy are useful in clinical practice and in research with PD patients with and without cognitive impairment.     

Impact of drooling in Parkinson’s disease

Drooling is a well known problem in patients with Parkinson's disease (PD). The aim of this study was to investigate the severity and consequences of drooling in PD. A comprehensive drooling questionnaire was sent to 105 PD outpatients, who had volunteered drooling during a previous questionnaire (n = 216). Among 63 patients who responded and confirmed drooling, 27% experienced severe saliva loss. Social and emotional consequences were reported by 17% to 77% of patients, and significantly more often by those with severe drooling. We conclude that drooling is a frequent, disabling and apparently undertreated symptom of PD. History taking ought to be detailed and specific to understand the full impact of drooling for an individual patient. Therapeutic options should be evaluated more intensively.     

Pharmacotherapy of Parkinson’s disease in Germany

Treatment standards or guidelines have been developed for most features of Parkinson’s disease (PD). However, data on the actual treatment that is put into practice are scarce. In 2000, a nationwide survey on the topic of sudden onset of sleep (SOS) in PD was initiated among the members of the German patient support group (deutsche Parkinson–Vereinigung, dPV). A part of this mailed questionnaire survey covering the antiparkinsonian and concomitant medication of the participants is presented here. This study analyses data sets from more than 6,500 PD patients. The mean dopaminergic dose was equivalent to 599 ± 387 mg levodopa/die. The most frequently administered drugs were levodopa (94.2 %), dopamine agonists (DA) (71.7 %), amantadine (40.1 %), selegiline (27.6 %), entacapone (20.4 %), budipine (12.3 %), and anticholinergics (11.8 %). Costs of pharmacotherapy were estimated to be approximately € 399 million/year in Germany. PD drug therapy in general strongly depended on age, disease duration, and the level of care. The treatment guidelines were apparently not consistently followed underlining the need for their continuous propagation throughout the medical community. In addition our data suggest that non–motor symptoms in PD are not adequately treated and that concomitant sedative medication contributes to the occurrence of SOS.     

Nanoparticles for drug delivery in Parkinson’s disease

Journal of Neurology - Although effective symptomatic treatments for Parkinson’s disease (PD) have been available for some time, efficient and well-controlled drug delivery to the brain has...     

Repurposed drugs for use in Parkinson’s disease

Journal of Neurology -     

Neuroimaging in Parkinson’s disease

In this review, the potential role of positron emission tomography and single photon emission computed tomography as biological markers for diagnosing and following the progression of Parkinson’s disease (PD) is discussed. Their value for assessing the efficacy of putative neuroprotective agents in PD and for revealing the pharmacological changes underlying the symptomatology and complications of this disorder is also considered. It is concluded that in the future functional imaging will provide a valuable adjunct to clinical assessment when judging the efficacy of putative neuroprotective approaches to PD.     

Fatigue in Parkinson’s disease

Abstract. Fatigue is a recognized problem in Parkinsons disease and other clinical conditions. We characterized this symptom in 19 patients and 19 age- and sex-matched controls, using the Multidimensional Fatigue Inventory (MFI) and the Geriatric Depression Scale. Fatigue may be an independent symptom in Parkinsons disease, frequently associated with depression. Our analysis showed the usefulness of the MFI in discriminating between different dimensions of fatigue for a better therapeutic approach.     

Depression in Parkinson’s disease

Among the recently well appreciated non-motor symptoms in Parkinson’s disease (PD), depression plays a prominent role due to its frequency and impact on quality of life. However, depression may be confounded by motor symptoms, especially akinesia and other non-motor symptoms such as apathy, anxiety and dementia. Data on specific diagnostic tools or treatment for depressive symptoms in PD patients are still sparse. Here we summarize an expert opinion based on available data and clinical experience.

     

Instruments for holistic assessment of Parkinson’s disease

Assessment of Parkinson’s disease is a complex matter as a consequence of the variety of manifestations and complications that can be present in a patient. Although a really holistic assessment is probably a utopia, a comprehensive evaluation is possible using a combination of measures completed by health professionals, patients and/or caregivers. In PD, main domains requiring assessment include motor impairment, motor complications, non-motor symptoms, disability, and patient-reported outcomes. Such scales like the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale and the battery of Scales for Outcomes in Parkinson’s disease (SCOPA) provide a wide information on the most relevant aspects of the disease. Hoehn and Yahr staging, global impression, and quality of life measures furnish summarized whole evaluations and comprehensive non-motor symptom assessments help to identify and evaluate this kind of manifestations. This article shows a pragmatic review of common instruments (rating scales and questionnaires) usable for a comprehensive assessment of PD and provides information about sources for guiding the selection of measures and outcome analyses.     

Depression in Parkinson’s disease

Abstract Objectives The pathophysiology of depression and anxiety in Parkinson's disease remains obscure. We aimed to compare the fractional anisotropy (FA) values of Parkinson's disease (PD) patients with and without depression to investigate the nature of depression in PD. Methods Twenty-eight patients were divided into two groups: those with depression and those without. Diagnosis of depression was made using the DSM-IV criteria. Patients in the two groups were matched for Hoehn Yahr stage. Results There were significant reductions in FA values in the bilateral frontal ROIs possibly representing anterior cingulate bundles. Conclusions The anterior cingulate bundles play an important role in depression in PD, and some aspects of depression in PD have pathological processes in common with de novo depression.     

Cancer in Parkinson’s disease

INTRODUCTIONWe examined the prevalence of cancer in patients with Parkinson’s disease (PD) and controls evaluated at the Mayo Clinic in Jacksonville, Florida, between 2003 and 2014.METHODSWe retrospectively collected information regarding cancer diagnoses and diagnosis of PD from 971 unrelated PD patients and 478 controls, and all were white. For PD patients, we examined cancers diagnosed before and after PD diagnosis separately in addition to considering all cancer diagnoses.RESULTSTwenty different cancers were identified. In PD patients, the most common types of cancer were skin cancer (17.3% overall; 10.6% before PD), followed by nonmelanoma skin cancer (16.0% overall; 9.7% before PD), prostate cancer in men (12.8% overall; 9.2% before PD), breast cancer in women (10.6% overall; 6.3% before PD), and melanoma (2.4% overall; 1.1% before PD). Compared to controls, a significantly lower frequency of nonmelanoma skin cancer (odds ratio [OR]: 0.62, P = 0.0024) and any skin cancer (OR: 0.57, P = 0.0002) was observed in PD patients. These differences were greater when considering only cases with cancers that occurred before PD diagnosis (OR: 0.49, P < 0.0001; OR: 0.45, P < 0.0001, respectively), and there was a lower frequency of melanoma and any cancer preceding PD diagnosis compared to controls (OR: 0.31, P = 0.003; OR: 0.36, P < 0.0001). There was no evidence of a frequency difference for any other cancer.CONCLUSIONSPD patients had a lower frequency of skin cancers or any cancer prior to PD diagnosis compared to controls, suggesting that cancer may have a protective effect on PD risk.     

Depression in Parkinson’s disease

Depression is common in Parkinson’s disease (PD), and its identification and treatment are critically important in disease management. Despite depression’s high prevalence and major impact on patient quality of life, questions remain regarding its epidemiology and preferred treatment. The authors of this paper summarize available information on the epidemiology of depression in PD, review treatment options, and discuss possible interactions between antidepressants and other agents. This information may help guide clinical treatment and define the need for further studies.     

Aetiopathogenesis of Parkinson’s disease

Parkinson’s disease (PD) is characterised both clinically and pathologically by features that distinguish it from other parkinsonian disorders including, for instance, multiple system atrophy and progressive supranuclear palsy. The aetiologies of PD includes both genetic and environmental influences. Several single gene causes of autosomal dominant and recessive PD have been described. Recent genome-wide association (GWA) studies have identified a number of risk alleles for PD. No specific environmental cause has been defined but several factors have been described which influence the risk for PD. Mitochondrial dysfunction, free radical mediated damage, inflammatory change and proteasomal dysfunction have been thought to play a role in PD pathogenesis. Autophagy is now recognised as an important component of the cell’s mechanism for protein turnover and has relevance for PD. There is some convergence and overlap of pathogenetic pathways between environmental and genetic factors. The importance of identifying the molecular and biochemical events that lead to PD lies in the prospect that novel drug targets will emerge and that new compounds will be developed that slow the progression of the disease.

     

Pathoanatomy of Parkinson’s disease

Parkinson’s disease is a widespread degenerative illness affecting the human central, peripheral, and enteric nervous systems. The underlying pathological process progresses slowly but relentlessly and involves multiple neuronal systems. The disease is the consequence of changes in the neuronal cytoskeleton developing in only a few susceptible types of nerve cells. Afflicted neurons eventually produce Lewy bodies in their perikarya and Lewy neurites in their neuronal processes.

Immunoreactions against the presynaptic protein α-synuclein have revealed many kinds of inclusion bodies ranging from inconspicuous dot- or thread-like forms to particularly voluminous types. The selective vulnerability of nerve cells induces a distinctive distribution pattern of lesions which remains remarkably consistent across cases. Components of the limbic system and the motor system have been shown to be particularly vulnerable to severe destruction. Some subnuclei of the substantia nigra also undergo major changes. This damage is consistently accompanied by extranigral alterations, with predilection sites including the entorhinal region, the second sector of the Ammon’s horn, and important subnuclei of the amygdala. In addition, the nucleus of the stria terminalis, components of the hypothalamus, all of the non-thalamic nuclei with diffuse projections to the cerebral cortex, and most of the centers regulating autonomic functions exhibit severe lesions.