[Show abstract][Hide abstract] ABSTRACT: Identification of risk factors and prodromal markers for Parkinson's disease (PD) and the understanding of the point in time of first occurrence is essential for the early detection of incident PD. In this three-center longitudinal, observational study, we evaluated the specific risk for PD associated with single or combinations of risk factors and prodromal markers. In addition, we evaluated which risk factors and prodromal markers emerge at which time before the diagnosis of PD. Of the 1,847 at-baseline PD-free individuals ≥50 years, 1,260 underwent the 5-year follow-up assessment. There were 21 cases of incident PD during the study period. Enlarged hyperechogenic substantia nigra was the most frequent baseline sign in individuals developing PD after 3 years (80.0 %) and 5 years (85.7 %) compared to healthy controls (17.5 %) followed by the occurrence of mild parkinsonian signs and hyposmia. Evaluation of the signs at the first follow-up assessment showed that individuals developing PD after two additional years showed the same pattern of signs as individuals who developed PD 3 years after baseline assessment.
Journal of Neurology 11/2013; · 3.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Although gait disorders are common in the elderly, the prevalence and overall burden of these disorders in the general community is not well defined.
In a cross-sectional investigation of the population-based Bruneck Study cohort, 488 community-residing elderly aged 60-97 years underwent a thorough neurological assessment including a standardized gait evaluation. Gait disorders were classified according to an accepted scheme and their associations to falls, neuropsychological measures, and quality of life were explored.
Overall, 32.2% (95% confidence interval [CI] 28.2%-36.4%) of participants presented with impaired gait. Prevalence increased with age (p<0.001), but 38.3% (95%CI 30.1%-47.3%) of the subjects aged 80 years or older still had a normally preserved gait. A total of 24.0% (95%CI 20.4%-28.0%) manifested neurological gait disorders, 17.4% (14.3%-21.0%) non-neurological gait problems, and 9.2% (6.9%-12.1%) a combination of both. While there was no association of neurological gait disorders with gender, non-neurological gait disorders were more frequent in women (p = 0.012). Within the group of neurological gait disorders 69.2% (95%CI 60.3%-76.9%) had a single distinct entity and 30.8% (23.1%-39.7%) had multiple neurological causes for gait impairment. Gait disorders had a significant negative impact on quantitative gait measures, but only neurological gait disorders were associated with recurrent falls (odds ratio 3.3; 95%CI 1.4-7.5; p = 0.005 for single and 7.1; 2.7-18.7; p<0.001 for multiple neurological gait disorders). Finally, we detected a significant association of gait disorders, in particular neurological gait disorders, with depressed mood, cognitive dysfunction, and compromised quality of life.
Gait disorders are common in the general elderly population and are associated with reduced mobility. Neurological gait disorders in particular are associated with recurrent falls, lower cognitive function, depressed mood, and diminished quality of life.
PLoS ONE 07/2013; 8(7):e69627. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: The clinical diagnosis of Parkinson's disease (PD) is currently anchored in its cardinal motor symptoms. According to hospital-based studies, an enlarged echogenicity in the area of the substantia nigra (SN) assessed with transcranial sonography (TCS) may represent a useful biomarker in the diagnosis of PD. Objective: To evaluate SN hyperechogenicity as a marker for PD in the Bruneck Study cohort, which is representative of the general elderly community. Methods: The diagnostic accuracy of TCS in distinguishing clinically diagnosed PD from nonparkinsonian subjects was assessed in 574 subjects from this cohort. Results: There was a good diagnostic accuracy of TCS in distinguishing PD subjects from nonparkinsonian subjects with an area under the curve value of 0.82. At a receiver-operating characteristic curve analysis-based cutoff value for SN hyperechogenicity of 0.18 cm(2), TCS had a sensitivity of 88.2% (95% confidence interval, CI, 64.4-98.0), a specificity of 77.0% (95% CI 72.8-80.6), a positive predictive value of 12.7% (95% CI 7.8-20.0) and a negative predictive value of 99.4% (95% CI 97.8-100.0) for subjects with clinically definite PD at baseline. When analyzing the same population after 5 years with regard to the presence of known and newly diagnosed PD cases, baseline TCS yielded very similar diagnostic accuracy values. Conclusion: SN hyperechogenicity may represent a useful biomarker for PD not only in a hospital-based setting but also in the general community.
[Show abstract][Hide abstract] ABSTRACT: Pentraxins like C-reactive protein are key components of the innate immune system. Recently, pentraxin-3 (PTX3) has been proposed to be a specific marker of vascular inflammation, yet its association with atherosclerosis is still unclear.
PTX3 serum levels were measured in three independent studies of 132 young men (ARMY Study), 205 young women (ARFY Study) and 562 individuals 55 to 94 years old (Bruneck Study). In contrast to C-reactive protein, PTX3 showed little relationships with classic vascular risk factors and pro-inflammatory conditions. In the population based Bruneck Study, PTX3 level was independently associated with prevalent cardiovascular diseases (multivariable odds ratio [95%CI] 3.09 [1.65-5.79]; P<0.001). Moreover, PTX3 level correlated with the severity of carotid and femoral atherosclerosis and was highest in individuals with multiple vascular territories affected. In contrast, there was no association with elevated intima-media thickness, a precursor lesion of atherosclerosis, in any of the three populations investigated.
Level of PTX3 is independently associated with atherosclerosis and manifest cardiovascular disease but not early vessel pathology. Unlike C-reactive protein, PTX3 is not a component of the classic acute phase response (systemic inflammation) but appears to be more specific for vascular inflammation.
PLoS ONE 02/2012; 7(2):e31474. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate whether enlarged substantia nigra hyperechogenicity (SN+) is associated with an increased risk for Parkinson disease (PD) in a healthy elderly population.
Longitudinal 3-center observational study with 37 months of prospective follow-up.
Individuals 50 years or older without evidence of PD or any other neurodegenerative disease.
Of 1847 participants who underwent a full medical history, neurological assessment, and transcranial sonography at baseline, 1535 could undergo reassessment.
Incidence of new-onset PD in relation to baseline transcranial sonography status.
There were 11 cases of incident PD during the follow-up period. In participants with SN+ at baseline, the relative risk for incident PD was 17.37 (95% confidence interval, 3.71-81.34) times higher compared with normoechogenic participants.
In this prospective study, we demonstrate for the first time a highly increased risk for PD in elderly individuals with SN+. Transcranial sonography of the midbrain may therefore be a promising primary screening procedure to define a risk population for imminent PD.
Archives of neurology 07/2011; 68(7):932-7. · 7.58 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To determine the association between leukocyte telomere length (TL) and atherosclerosis and its clinical sequelae stroke and myocardial infarction.
Within the scope of the prospective population-based Bruneck Study, leukocyte TL was measured by quantitative polymerase chain reaction in 800 women and men aged 45 to 84 years (in 1995). The manifestation of cardiovascular disease (CVD) (1995-2005) and the progression of atherosclerosis (1995-2000) were carefully assessed. The TL was shorter in men than in women (age-adjusted mean [95% CI], 1.41 [1.33 to 1.49] versus 1.55 [1.47 to 1.62]; P=0.02) and inversely correlated to age (r=-0.22, P<0.001) and family history of CVD (P=0.03). Participants with CVD events during follow-up (n=88) had significantly shorter telomeres (age- and sex-adjusted mean [95% CI], 1.25 [1.08 to 1.42] versus 1.51 [1.45 to 1.57]; P<0.001). In multivariable Cox models, baseline TL emerged as a significant and independent risk predictor for the composite CVD end point and its individual components (myocardial infarction and stroke); however, this was not the case for de novo stable angina and intermittent claudication. Subjects in the top and bottom TL tertile group differed in their CVD risk by a factor of 2.72 (95% CI, 1.41 to 5.28), which is the risk ratio attributable to a 13.9-year difference in chronological age. Remarkably, in our atherosclerosis progression model, TL was strongly associated with advanced, but not early, atherogenesis. All findings were consistent in women and men.
Our findings indicate a differential role of telomere shortening in the various stages of atherosclerosis, with preferential involvement in advanced vessel pathology and acute vascular syndromes.
[Show abstract][Hide abstract] ABSTRACT: Previous studies have yielded evidence of an enhanced risk of cardiovascular disease, especially stroke, among patients with migraine. Our understanding of the underlying mechanisms is far from complete. The aims of the present study were to investigate the potential association between migraine and atherosclerosis and to assess the risk of venous thromboembolism as a clinical surrogate for a procoagulant state in patients with migraine.
The examination was part of the population-based Bruneck Study. During the 2005 evaluation, 574 participants aged 55-94 years underwent neurologic and laboratory examinations involving a standardized headache interview and scanning of the carotid and femoral arteries to evaluate presence, severity, and progression (2000-2005) of atherosclerosis.
A large number of well-founded and putative cardiovascular risk factors have emerged as being unrelated to migraine status. Prevalence, severity, and 5-year progression of carotid and femoral atherosclerosis did not differ significantly between migraineurs with and without aura and nonmigraineurs. In fact, there was even a tendency for atherosclerosis to be less pronounced among patients with migraine, and for the intima-media thickness to be lower (p = 0.029). As a novel finding migraineurs faced a significantly enhanced risk of venous thromboembolism (18.9% vs 7.6% in nonmigraineurs, age/sex-adjusted p = 0.031).
This study is the first to compare the burden of atherosclerosis as quantified by high-resolution duplex ultrasound between migraineurs and nonmigraineurs in the general community, and provides solid evidence against the view that migraine predisposes to atherosclerosis. The higher risk for venous thromboembolism among migraineurs (prothrombotic state) awaits confirmation and elaboration in future research.
[Show abstract][Hide abstract] ABSTRACT: The aim of the current study was to estimate the prevalence of all primary headaches and cranial neuralgias in the general community. As part of the population-based Bruneck Study, 574 men and women aged 55-94 years underwent extensive neurological and laboratory examinations involving a standardized headache interview. In the Bruneck Study population the lifetime prevalence of all primary headaches combined and of cranial neuralgias was 51.7 and 1.6%, respectively. Tension-type headache (40.9%) and migraine (19.3%) emerged as the most common types of headache. In men and women aged 55-94 years the 1-year prevalence of primary headaches was high at 40.5%. In this age range headaches caused significant impairment of health-related quality of life. The Bruneck Study has confirmed the high lifetime prevalence of primary headaches and cranial neuralgias in the general population and provided first valid prevalence data for all primary headaches based on International Classification of Headache Disorders, 2nd edition criteria.
[Show abstract][Hide abstract] ABSTRACT: Fragestellung: Wie hoch ist die Prävalenz von Bewegungsstörungen mit Einbeziehung der geschlechtsspezifischen Unterschiede und Alterstendenz? Hintergrund: Obwohl Bewegungsstörungen den größten Prozentsatz neurologischer Erkrankungen bei älteren Erwachsenen darstellen, ist deren Prävalenz im deutschsprachigen Raum nicht gut untersucht. Methodik:
[Show abstract][Hide abstract] ABSTRACT: There is emerging awareness that movement disorders rank among the most common neurological diseases. However, the overall burden of these disorders in the general community is not well defined. We sought to assess the prevalence of all common categories of movement disorders in a population, accounting for sex differences and age trends.
As part of an ongoing prospective population-based study of carotid atherosclerosis and stroke risk (the Bruneck Study), a total of 706 men and women aged 50-89 years underwent a thorough neurological assessment. The diagnosis of movement disorders and ratings for disease severity were based on standard criteria and scales. Prevalences were estimated from logistic regression models (regression-smoothed rates) and standardised to the age and sex structure of the general community.
The prevalence of all common categories of movement disorders was 28.0% (95% CI 25.9-30.1). Proportions in men (27.6% [95% CI 24.5-30.7]) and women (28.3% [25.5-31.2]) were closely similar and sharply increased with age (from 18.5% [15.0-22.0] in 50-59-year olds to 51.3% [44.9-57.7] in 80-89-year olds). Almost half of all patients (90/214) had moderate-to-severe disease expression, but only 7.0% (15/214) received standard drug treatment. Prevalence of tremor was 14.5%, followed by restless legs syndrome (10.8%), parkinsonism (7%), primary dystonia and secondary dystonia (1.8%), and chorea and tics (<1% each). A fifth of all movement disorders were diagnosed to be probably drug-induced.
There is a high prevalence of and substantial under-recognition and under-treatment of movement disorders in the general community.
The Lancet Neurology 12/2005; 4(12):815-20. · 21.82 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To assess the prevalence and severity of restless legs syndrome (RLS) in the general community and to investigate its potential relationship with iron metabolism and other potential risk factors.
This was a cross-sectional study of a sex- and age-stratified random sample of the general population (50 to 89 years; n = 701). The diagnosis of RLS was established by face-to-face interviews; severity was graded on the RLS severity scale. Each subject underwent a thorough clinical examination and extensive laboratory testing.
The prevalence of RLS was 10.6% (14.2% in women, 6.6% in men); 33.8% of all patients with RLS had mild, 44.6% had moderate, and 21.6% had severe disease expression. None had been previously diagnosed or was on dopaminergic therapy. Free serum iron, transferrin, and ferritin concentrations were similar in subjects with and without RLS. However, soluble transferrin receptor (sTR) concentrations were different in subjects with and without RLS (1.48 vs 1.34 mg/L; p < 0.001). Female sex and high sTR independently predicted the risk of RLS.
This large survey confirms the high prevalence, female preponderance, and underrecognition of restless legs syndrome in the general community. Although two-thirds of patients had moderate to severe disease, none was on current dopaminergic therapy.
[Show abstract][Hide abstract] ABSTRACT: The prevalence of primary dystonia was assessed in a random population sample of individuals aged 50 and over in Bruneck, South Tyrol. The diagnosis of primary dystonia was confirmed by videotaped review. Primary dystonia was present in 6 of 707 cases resulting in a prevalence rate of 732 per 100,000 (95% CI 319-1,564) in the general population aged 50 and over. Only two cases (33%) had been previously diagnosed. These results indicate that the true prevalence of primary dystonia is significantly higher than published rates.
[Show abstract][Hide abstract] ABSTRACT: The potential role of activated protein C (APC) resistance in arterial thrombosis and disease is a matter of ongoing controversy.
In the present population-based survey, a random sample of 826 men and women underwent high-resolution duplex ultrasound scanning of the carotid and femoral arteries. Response to APC was expressed in APC ratios. Subjects were tested for the factor V Leiden mutation. The risk of carotid stenosis increased gradually with decreasing response to APC (adjusted OR [95% CI] for a 1-U decrease of response to APC, 1.6 [1. 2 to 2.2]), as did the risk of femoral artery stenosis (1.7 [1.3 to 2.3]) and prevalent cardiovascular disease (1.4 [1.1 to 2.0]). The association between low APC ratio and atherosclerotic vascular disease applied equally to subjects with the factor V Leiden mutation and those without. Our study identified various nongenetic determinants of poor response to APC in the general population, including behavioral, hormonal, and environmental factors.
The present study revealed an independent and gradual association between low response to APC and both advanced atherosclerosis (stenosis) and arterial disease. Resistance to APC due to factor V Leiden mutation was only one facet of this relationship.