Causes and consequences of falls in Parkinson disease patients in a prospective study

Background and purposeFalls are common events in Parkinson disease (PD) but only a few prospective studies have focused on causes and consequences of falls in PD patients. The aim of the study was prospective analysis of direct causes and consequences of falls in PD patients in comparison to the control group.Material and methodsOne hundred PD patients and 55 age-matched controls were enrolled in the study. The diagnostic workup in all patients included neurological examination, Unified Parkinson's Disease Rating Scale, magnetic resonance imaging, electroencephalography, ultrasonography, otolaryngological, ophthalmological and autonomic function examination. During 12 months of follow-up, falls were registered in both groups, direct causes were classified according to the St. Louis and Olanow classification, and consequences were established.ResultsFalls occurred in 54% of PD patients and in 18% of control subjects. Analysis of direct causes of falls revealed that sudden falls were the most common (31%), followed by episodes of freezing and festination (19.6%), neurological and sensory disturbances (mostly vertigo) (12%), environmental factors (12%), postural instability (11%), orthostatic hypotension (4%), and severe dyskinesia (3.6%); 6.19% of falls were unclassified; 22% of patients had the same etiology of subsequent falls. In PD patients, intrinsic factors were dominant, whereas in the control group intrinsic and extrinsic factors occurred with the same frequency. Every third fall intensified fear of walking. 34% of falls caused injuries; among them bruises of body parts other than the head were most frequent.ConclusionsIntrinsic factors are the most common causes of falls in PD. Every third fall intensifies fear of walking and causes injuries.     

The incidence and risk factors of falls in Parkinson disease: prospective study

Background and purposeAlthough Parkinson disease (PD) patients suffer falls more frequently than other old people, only a few studies have focused on identifying the specific risk factors for falls in PD patients. The aim of this study was to assess the incidence and risk factors of falls in a prospective study in comparison to a control group.Material and methodsOne hundred patients with PD were recruited to the study along with 55 gender- and age-matched healthy controls. Both groups were examined twice; the second examination took place one year after the first one. Examination of the PD group included: medical history including falls, neurological examination, assessment of the severity of parkinsonism [Unified Parkinson's Disease Rating Scale (UPDRS), Schwab and England scale (S&E), Hoehn and Yahr scale (H&Y), Mini-Mental State Examination (MMSE)], Hamilton scale and quality of life scales (SF-36, EQ-5D) and Freezing of Gait Questionnaire (FOG-Q). In both groups falls were recorded over the 12 months. Frequent fallers are defined as having more than 3 falls a year.ResultsOver the year falls occurred in 54% of PD patients and 18% of controls. In a prospective study 28% of PD patients fell more frequently than in retrospective analysis. Frequent fallers were found in 20% of patients and in 7% of controls. Fallers showed higher scores in UPDRS, H&Y, S&E, MMSE, and Hamilton scale than non-fallers. Independent risk factors for falls were: age, previously reported falls and higher score in the FOG-Q.ConclusionsFalls in PD patients occurred three times more frequently than in controls. Independent risk factors for falls were: high score in FOG-Q, older age and presence of falls in medical history.     

Motor complications in Parkinson disease: a prospective follow-up study

Currently, Parkinson disease (PD) can be symptomatically controlled with standard treatments; however, after a few years this response typically declines. The authors carried out a prospective practice-based study to evaluate the evolution and motor complications during the first 5 years in 59 de novo PD patients. They observed a significant improvement in UPDRS scores during the first year, then the UPDRS mean score declined progressively, especially after the third year (UPDRS score at baseline, 27 points; year 1, 19 points; year 2, 20.3 points; year 3, 22.6 points; year 4, 24.9 points; year 5, 29.5 points). Motor fluctuations, dyskinesias, and freezing also increased after year 3 from 10%, 16%, and 8% respectively to 35%, 32%, and 27% at year 5. At 5 years, 50% of patients (30 of 59) still had UPDRS scores better or equal to baseline, and 44% (26 of 59) had no motor complications. This latter group represented 38% of those subjects initially treated with levodopa and 52% initially treated with other agents.     

Cardiovascular autonomic nervous system evaluation in Parkinson disease and multiple system atrophy

BackgroundAutonomic nervous system dysfunction (ANSd) heralds or follows motor symptoms (MS) in Parkinson disease (PD), but may precede years and progress more rapidly in multiple system atrophy (MSA). Cardiac dysautonomia severity correlates with disabling symptoms thus a Cardiac Autonomic Nervous System Evaluation protocol (CANSEp) is useful to assess ANSd in PD and MSA patients.Methods and resultsConsecutive patients with PD or MSA were studied. The severity of MS was quantified with UPDR III and Hoehn/Yahr scales. CANSEp consisted of the 5-test Ewing protocol (EP) and Heart Rate Variability analysis (HRVa), in time-domain (TD) and frequency-domain (FD).36 patients with parkinsonian symptoms (23 PD, 13 MSA) and 40 healthy controls were studied. Parkinsonism was more severe in MSA, comparing UPDR III and Hoehn/Yahr scales (p < 0.0001). Higher EP's scores were found in MSA (mean 5.1 ± 1.98) compared to PD (mean 3.5 ± 2) and controls (score 0.25 ± 0.1). TD and FD-HRVa were abnormal in PD and MSA, compared to controls. In PD depression of vagal tone was predominant during sleep, whereas in MSA depression of sympathetic tone prevailed during daily activity.ConclusionsWhereas its specificity is very high, the sensitivity of the EP was only 43.5% in PD and 76.9% in MSA. HRVa improved diagnosis accuracy in 10 patients, unidentified by the EP alone, with overall sensitivity of 65.2% in PD and 92.3% in MSA. Thus CANSEp provides a better assessment of cardiovascular dysautonomia in parkinsonian syndromes, useful to differentiate PD from MSA and to address clinical and pharmacological management.     

Incidence and prediction of falls in Parkinson's disease: a prospective multidisciplinary study

OBJECTIVES: To accurately establish the incidence of falls in Parkinson's disease (PD) and to investigate predictive risk factors for fallers from baseline data. METHODS: 109 subjects with idiopathic PD diagnosed according to the brain bank criteria underwent a multidisciplinary baseline assessment comprising demographic and historical data, disease specific rating scales, physiotherapy assessment, tests of visual, cardiovascular and autonomic function, and bone densitometry. Patients were then prospectively followed up for one year using weekly prepaid postcards along with telephone follow up. RESULTS: Falls occurred in 68.3% of the subjects. Previous falls, disease duration, dementia, and loss of arm swing were independent predictors of falling. There were also significant associations between disease severity, balance impairment, depression, and falling. CONCLUSIONS: Falls are a common problem in PD and some of the major risk factors are potentially modifiable. There is a need for future studies to look at interventions to prevent falls in PD.     

Dementia and Alzheimer disease incidence: a prospective cohort study

CONTEXT: Age-specific incidence rates for dementia and Alzheimer disease (AD) are important for research and clinical practice. Incidence estimates for the United States are few and vary with the population sampled and study design; we present data that will contribute to a consensus of these rates. OBJECTIVES: To provide age-specific incidence estimates for dementia and AD and to estimate the association of sex, educational level, and apolipoprotein E genotype with onset. DESIGN: Prospective cohort study; begun in 1994 with follow-up interviews every 2 years. SETTING: Members of community-based, large health maintenance organization with demographics consistent with the surrounding base population; diagnostic evaluation by university-based study clinicians. SUBJECTS: Random sample of subjects aged 65 years or older from the base population; dementia free, nonnursing home residents. Of 5422 who were eligible, 2581 were enrolled, and 2356 had at least 1 follow-up evaluation (10 591 person-years of observation). MAIN OUTCOME MEASURE: Dementia and Alzheimer disease diagnoses were based on standard criteria. Age-specific incidence rates were calculated using a person-years approach with Poisson distribution confidence intervals. Cox proportional hazards model analysis was used to examine other factors. RESULTS: Two hundred fifteen cases of dementia and 151 cases of AD were diagnosed. Incidence rates for dementia and AD increase across the 5-year age groups; AD rates rise from 2.8 per 1000 person-years (age group, 65-69 years) to 56.1 per 1000 person-years in the older than 90-year age group. The rates nearly triple from the 75-to-79-year and 80-to-84-year age groups, but the relative increase is much less thereafter. Sex was not associated with AD onset. Educational level (>15 years vs <12 years) was associated with a decreased risk of AD; however, the association was also dependent on the baseline cognitive screening test score. CONCLUSIONS: Our dementia and AD incidence rates are consistent with recent US and European cohort studies, providing clinicians and researchers new information concerning the reproducibility of incidence estimates across settings. Increased risk was associated with age and the apolipoprotein E genotype; also with a low baseline cognitive screening test score. Educational level was inversely associated with the risk of dementia and positively associated with the baseline cognitive test score; thus, detection of AD by the screening test could also be influenced by educational level.     

Cardiovascular autonomic responses in patients with Parkinson disease to pedunculopontine deep brain stimulation

Clinical Autonomic Research - Dysautonomia can be a debilitating feature of Parkinson disease (PD). Pedunculopontine nucleus (PPN) stimulation may improve gait disorders in PD, and may also result...     

Natural history of falls in a population-based cohort of patients with Parkinson's disease: An 8-year prospective study

BackgroundProspective long-term studies of falls in Parkinson's disease (PD) are scarce.ObjectiveTo examine the development of falls over 8 years in a population-based cohort of ambulatory patients with PD, and to investigate predictors of future falls in non-fallers at baseline.MethodsAll patients were examined at baseline and after 4 and 8 years, including the UPDRS, MMSE, Montgomery and Aaberg Depression Rating Scale, Functional Comorbidity Index, and a clinical dementia interview. Logistic regression models were applied to investigate baseline risk factors for future falls. A total of 211 patients were included at baseline, whereas 121 and 64 were re-examined at 4 and 8 years, respectively.ResultsThe prevalence of falls increased from 41% (87 of 211) at baseline to 72% (46 of 64) after 8 years of prospective follow-up (disease duration 16.2 ± 4.8 years). Forty-seven non-falling patients at baseline completed all study visits, of these 68% (n = 32) changed fall status during follow-up. Predictive variables for current falling after 4 years were rare or occasional freezing of gait (OR 6.6, 95% CI 1.2–36.9), higher levodopa equivalent doses and more severe speech and axial impairment (both OR 1.3, 95% CI 1.0–1.7) in non-fallers at baseline. Higher baseline age was the only risk factor for current falling after 8 years.ConclusionsNearly ¾ of the PD cohort reported falling after 8 years of follow-up. Disease-specific gait and axial impairments were the major risk factors for future falls in non-fallers at baseline. This has implications for patient education and management.     

Cardiovascular reflexes in Parkinson disease

We have investigated the autonomic function of 95 patients with Parkinson disease (PD) by testing their cardiovascular reflexes and compared the results with those of 53 healthy volunteers. 51.1% of the patients were on antiparkinsonian therapy. The patients showed a smaller heart rate response to deep breathing with a mean exhalation-inspiration difference of 87.73±7 (p: 0.0005), a smaller heart rate response to standing with a mean 30 ∶ 15 index of 1.18±0.25 (p∶ 0.01), and a smaller blood pressure rise to handgrip with a mean rise of 9.53±8.76 mmHG (p∶ 0.005). We found a higher percentage of patients with established sympathetic lesion (41% vs 34%) or atypical patterns of global autonomic function involvement (33% vs 26%), but the percentage of subjects with parasympathetic lesion was similar in both, patients and controls (16% vs 15%). We found no significant difference on cardiovascular performance between treated and untreated patients. The patients with autonomic impairment were older than the patients with normal autonomic function. Our findings suggest that patients with PD have a true autonomic dysfunction.

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Sommario Abbiamo studiato la funzionalità del Sistema Nervoso Autonomo in 95 pazienti affetti da Malattia di Parkinson (PD), valutando i riflessi cardiovascolari e confrontando i risultati con quelli ottenuti da 53 volontari sani. Il 51.1% dei pazienti Parkinsoniani era in trattamento farmacologico. I pazienti hanno mostrato una ridotta risposta della frequenza cardiaca alla ventilazione profonda, alla stazione eretta e un ridotto aumento pressorio dopo esercizio isometrico. è stata riscontrata una più alta percentuale di pazienti con lesioni simpatiche stabilite (41% vs 34%) e con quadro atipico di coinvolgimento globale della funzione autonomica (33% vs 26%), ma la percentuale di soggetti con lesioni parasimpatiche era simile nei pazienti e nei soggetti di controllo (16% vs 15%). Non è stata riscontrata una significativa differenza alle performance cardiovascolari tra pazienti in trattamento farmacologico e non trattati. I pazienti con disturbi autonomici erano più anziani di quelli con normale funzione autonomica. I dati suggeriscono la presenza di una vera disfunzione autonomica nei pazienti affetti da PD.

     

帕金森病心脏自主神经功能障碍的研究进展

自主神经功能障碍是帕金森病较为常见的非运动症状,其发生率会随着帕金森病情的进展而升高.自主神经功能障碍常累及心脏,导致心血管调节功能障碍,从而出现一系列临床症状.现就心脏自主神经功能障碍的常见症状、发病机制和治疗措施等方面的研究进展作一综述.     

Syncope and autonomic cardiovascular dysfunction in Parkinson disease

BACKGROUND AND PURPOSE : The aim of the study was to investigate the relationship between syncope or presyncope occurrence and dysfunction of the cardiovascular autonomic system in patients with Parkinson disease (PD). MATERIAL AND METHODS : Twenty-four PD patients were studied, including 10 subjects with syncope/presyncope and 14 con-trols without those symptoms. Ambulatory blood pressure monitoring (ABPM), Holter electrocardiographic monitoring, carotid sinus massage, tilt test, and cardiac scintigraphy with 123I metaiodobenzylguanidine (MIBG) were performed. RESULTS : Differences between the two groups were found in myocardial scintigraphy and ABPM. The stepwise regression analyses suggest that the values of late phase reduced uptake of MIBG (95% CI: 0.0-0.77; p < 0.05) and day-time minimum systolic blood pressure (95% CI: 0.78-0.98; p = 0.007) may be related to the occurrence of syncope/presyncope. CONCLUSIONS : The findings suggest an association between syncope/presyncope occurrence and dysfunction of the cardiovascular autonomic system in PD patients. Both 123I MIBG myocardial scintigraphy and ABPM may help identify a group of patients with an elevated risk for syncopic episodes which, in turn, may affect the choice of treatment.     

Cardiovascular autonomic neuropathy and other complications in type 1 diabetes

Objective and methods  

This study deals with cardiovascular autonomic neuropathy (CAN) in type 1 diabetic patients and its association with other complications. We searched for CAN in 684 patients (age, 47 ± 12 years; diabetes duration, 22 ± 11 years) by cardiovascular responses to deep breathing and standing. Patients considered as positive had laboratory evaluation: “Ewing” tests (deep breathing, Valsalva, stand test, hand grip); heart rate variability (HRV) [low frequency (LF) and high frequency (HF) power] and spontaneous baroreflex slope (SBS). Logistic regression was used to identify the combination of patient characteristics, including other complications, most associated with CAN severity according to Ewing Score (ES 0–5).     

Battery longevity of neurostimulators in Parkinson disease: A historic cohort study

BackgroundDeep brain stimulation (DBS) of the subthalamic nucleus (STN) is a well-established treatment for motor complications in Parkinson disease (PD). Since 2012, the nonrechargeable dual-channel neurostimulator available in France seems to have shorter battery longevity compared to the same manufacturer's previous model.ObjectiveThe aim of this study was to evaluate the battery longevity of older and more recent neurostimulators from the same manufacturer and to explore factors associated with battery life variations.Materials and methodsWe retrospectively studied our cohort of PD patients who underwent STN DBS between 1987 and 2017. We collected data concerning neurostimulator replacements and parameters. We compared the survival of the first device available, Kinetra® and the current one, Activa-PC® (Medtronic Inc.) and estimated the factors that had an impact on battery longevity through a Cox logistic regression.ResultsThree hundred sixty-four PD patients received a total of 654 DBS STN neurostimulators: 317 Kinetra® and 337 Activa-PC®. The survival analysis, using the Kaplan-Meier estimator, showed a difference between the curves of the two devices (log-rank test; p < 0.001). The median survival of an Activa-PC® neurostimulator was 1666 days, while it was 2379 days for a Kinetra®.After adjustment, according to the multivariate analysis, the main factors associated with battery lifetime were: the neurostimulator type; the number of subsequent neurostimulator implantations; the total electrical energy delivered (TEED); and sex.ConclusionThe Kinetra® neurostimulator lifetime is 2.5 years longer than the Activa-PC®. The type of the device, the high TEED and the number of subsequent neurostimulator implantations influence battery longevity most. These results have medical-economic implications since the survival of PD patients with DBS increases over years.     

Physical activity and risk of Parkinson's disease: a prospective cohort study

Background

Despite the fact that Parkinson''s disease is the second most common neurodegenerative disease, little is known about risk factors for the disease. Laboratory experiments indicate that physical activity may have a neuroprotective effect; however, there are few data on whether physical activity is associated with decreased risk of Parkinson''s disease.

Aim

To investigate the relationship between physical activity and Parkinson''s disease in 10 714 men (mean age, 67.6 years) from the Harvard Alumni Health Study, who were diagnosed as free of self‐reported Parkinson''s disease in 1988.

Methods

Physical activity was assessed in 1988 by asking about the daily number of blocks walked and stairs climbed, and participation in sports and recreational activities in the past week. Energy expenditure was then estimated and men were categorised into four groups: <1000, 1000–1999, 2000–2999 or ⩾3000 kcal/week. In addition, physical activity data were available for three past time points: during college, 1962 or 1966, and 1977. Incident cases of Parkinson''s disease occurring after 1988 (n = 101) were identified through a follow‐up health questionnaire in 1993 and death certificates obtained until 1997.

Results

In multivariate analyses, the relative risks (RR) for Parkinson''s disease associated with <1000, 1000–1999, 2000–2999 and ⩾3000 kcal/week of physical activity were 1 (referent), 1.15 (95% confidence interval (95% CI) 0.71 to 1.88), 0.92 (0.50 to 1.71) and 0.63 (0.36 to 1.12), respectively; p for trend was 0.12. When walking was examined separately, somewhat lower, but not significant, risks were observed for Parkinson''s disease. The multivariate RRs (95% CI) for walking <5, 5–10, 10–20 and >20 km/week were 1 (referent), 0.67 (0.37 to 1.23), 0.81 (0.50 to 1.31) and 0.72 (0.39 to 1.34), respectively; p for trend was 0.26. Analyses that considered physical activity at other time points before 1988 did not show any significant associations.

Conclusions

These data do not strongly support the hypothesis that physical activity lowers the risk of Parkinson''s disease. However, as the number of patients with Parkinson''s disease in this study was not large, statistical power may have been limited and further large studies are needed to provide additional data.Although Parkinson''s disease is the second most common neurodegenerative disease among those aged >65 years, the aetiology of Parkinson''s disease is not well understood. Only a few risk factors have been consistently identified, with both smoking and caffeine showing strong inverse associations with the disease¹ and family history showing a positive association.² Other risk factors such as specific foods or nutrients have been identified in some studies, but not in others.^3,4,5,6,7A potentially interesting and modifiable risk factor for Parkinson''s disease is physical activity. Physical activity has been shown to be inversely related to other neurodegenerative diseases such as Alzheimer''s disease and cognitive decline.^8,9 Animal models of Parkinson''s disease show that treadmill training resulted in the attenuation of dopamine depletion in the striatum compared with that in control animals.¹⁰ In other experiments, exercise training improved both behavioural and motor symptoms.¹¹ In humans, four previous studies have investigated the role of physical activity in preventing Parkinson''s disease.^12,13,14,15 In the only prospective study, men who exercised strenuously had a 60% decreased risk of Parkinson''s disease compared with men who did not, but no clear effect was observed in women.¹⁵ To provide additional prospective data, we evaluated the relationship between physical activity and risk of Parkinson''s disease in an ongoing study, the Harvard Alumni Health Study.     

Cardiovascular aspects of Parkinson disease

This chapter provides an update about cardiovascular aspects of Parkinson disease (PD), with the following topics: (1) Orthostatic hypotension (OH) as an early finding in PD; (2) neurocirculatory abnormalities in PD + OH independent of levodopa treatment; (3) cardiac and extracardiac noradrenergic denervation in PD + OH; (4) progressive loss of cardiac sympathetic innervation in PD without OH.     

Clinical features of late-onset Pompe disease: a prospective cohort study

The objective of this 12-month study was to describe the clinical features of late-onset Pompe disease and identify appropriate outcome measures for use in clinical trials. Assessments included quantitative muscle testing (QMT), functional activities (FAA), 6-min walk test (6MWT), and pulmonary function testing (PFT). Percent predicted values indicated quantifiable upper and lower extremity weakness, impaired walking ability, and respiratory muscle weakness. Significant declines in arm and leg strength and pulmonary function were observed during the study period. The outcome measures were demonstrated to be safe and reliable. Symptom duration was identified as the best predictor of the extent of skeletal and respiratory muscle weakness.