Patient's perception: shorter and more severe prodromal phase in GBA-associated PD.

Background: Prevalence and time of occurrence of prodromal symptoms of Parkinson's disease (PD) in relation to the onset of classical motor manifestation varies between patients. Possible modifying factors might be different genetic architectures predisposing to varying burden of manifestations.

Objectives: To characterize the prodromal phase in PD patients with heterozygous mutations in the GBA gene compared to PD patients without GBA mutation.

Association of Plasma Aβ40 Peptides, But Not Aβ42, with Coronary Artery Disease and Diabetes Mellitus.

Background/objective: Plasma levels of amyloid-beta (Aβ) 1-40 peptide have been proposed to be associated with cardiovascular mortality in patients with coronary artery disease (CAD). Therefore, we aimed to investigate the association of plasma Aβ levels with CAD, cardiovascular risk factors (CVRF), and APOE genotype in non-demented elderly individuals.

Methods: Plasma Aβ1 - 40 and Aβ1 - 42 levels of 526 individuals (mean age of 63.

Reasons for mild parkinsonian signs - which constellation may indicate neurodegeneration?

Introduction: Mild parkinsonian signs (MPS) are common in the elderly population. Several factors including physical decline and comorbidities in addition to neurodegeneration may be possible sources for MPS. The objective was to examine whether MPS are associated with a history of orthopedic disturbances, vascular diseases or prodromal markers for neurodegeneration.

Clinical characteristics related to worsening of motor function assessed by the Unified Parkinson's Disease Rating Scale in the elderly population.

There is evidence that nigrostriatal pathology may at least partly underlie mild Parkinsonian signs. We evaluated whether an increase in the Unified Parkinson's Disease Rating Scale part III (UPDRS-III) could be predicted by the presence of risk and prodromal markers for neurodegenerative diseases in elderly individuals without those diseases. Therefore, we analyzed the UPDRS-III score and various risk and prodromal markers known to antecede neurodegenerative diseases in a population-based cohort comprising 807 individuals free of neurodegenerative diseases at baseline.

Mild parkinsonian signs in the elderly--is there an association with PD? Crossectional findings in 992 individuals.

Background: Mild parkinsonian signs (MPS) are common in the elderly population, and have been associated with vascular diseases, mild cognitive impairment and dementia; however their relation to Parkinson's disease (PD) is unclear. Hypothesizing that individuals with MPS may reflect a pre-stage of PD, i.e.

Prodromal features for Parkinson's disease--baseline data from the TREND study.

Background And Purpose: A number of non-motor features are known to precede motor manifestations of Parkinson's disease (PD). They are supposed to already represent the prodromal neurodegenerative state in those who later develop PD and are thus called prodromal markers. In this study, three prodromal markers, depression, rapid eye movement behaviour disorder (RBD) and hyposmia, were selected and were related to other prodromal features in elderly individuals without PD.

Risk factors and prodromal markers and the development of Parkinson's disease.

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.

Cognitive profiles in Parkinson's disease and their relation to dementia: a data-driven approach.

Parkinson's disease is characterized by a substantial cognitive heterogeneity, which is apparent in different profiles and levels of severity. To date, a distinct clinical profile for patients with a potential risk of developing dementia still has to be identified. We introduce a data-driven approach to detect different cognitive profiles and stages.

Enlarged hyperechogenic substantia nigra as a risk marker for Parkinson's disease.

Background: SN hyperechogenicity (SN+), determined by transcranial sonography, has been proposed as a risk factor for Parkinson's disease (PD). Recently, we reported a 17.4-fold increased risk for PD in individuals with SN+ older than 50 years within 3 years.

The PRIPS study: screening battery for subjects at risk for Parkinson's disease.

Background And Purpose: Screening batteries to narrow down a target-at-risk population are essential for trials testing neuroprotective compounds aiming to delay or prevent onset of Parkinson's disease (PD).

Methods: The PRIPS study focuses on early detection of incident PD in 1847 at baseline PD-free subjects, and assessed age, male gender, positive family history, hyposmia, subtle motor impairment and enlarged substantia nigra hyperechogenicity (SN+).

Results: After 3 years follow-up 11 subjects had developed PD.

Lowered serum amyloid-β1-42 autoantibodies in individuals with lifetime depression.

Reduced levels of naturally occurring autoantibodies against amyloid-β (Aβ) have been described in Alzheimer's disease (AD). Lifetime depression doubles the risk of AD, thus these autoantibodies may also be reduced in this group. We measured serum IgG autoantibody titers against Aβ1-42, S100b and α-synuclein in 214 individuals with depression and 419 controls.

Poor trail making test performance is directly associated with altered dual task prioritization in the elderly--baseline results from the TREND study.

Background: Deterioration of executive functions in the elderly has been associated with impairments in walking performance. This may be caused by limited cognitive flexibility and working memory, but could also be caused by altered prioritization of simultaneously performed tasks. To disentangle these options we investigated the associations between Trail Making Test performance--which specifically measures cognitive flexibility and working memory--and dual task costs, a measure of prioritization.

Enlarged substantia nigra hyperechogenicity and risk for Parkinson disease: a 37-month 3-center study of 1847 older persons.

Objective: To evaluate whether enlarged substantia nigra hyperechogenicity (SN+) is associated with an increased risk for Parkinson disease (PD) in a healthy elderly population.

Design: Longitudinal 3-center observational study with 37 months of prospective follow-up.

Setting: Individuals 50 years or older without evidence of PD or any other neurodegenerative disease.

Influence of different cut-off values on the diagnosis of mild cognitive impairment in Parkinson's disease.

Comparable to Alzheimer's disease, mild cognitive impairment in Parkinson's disease (PD-MCI) is associated with an increased risk for dementia. However different definitions of PD-MCI may have varying predictive accuracy for dementia. In a cohort of 101 nondemented Parkinson patients who underwent neuropsychological testing, the frequency of PD-MCI subjects and PD-MCI subtypes (i.

The patients' perception of prodromal symptoms before the initial diagnosis of Parkinson's disease.

Background: Before the occurrence of motor symptoms permits the clinical diagnosis of Parkinson's disease (PD), about or even more than 50% of the dopaminergic neurons of the substantia nigra have degenerated. This time be called the prodromal phase of PD.

Objective: To evaluate the time span from onset of first prodromal symptoms to the initial diagnosis of PD as well as the order of symptom occurrence.

Relation of risk factors and putative premotor markers for Parkinson's disease.

As both risk and premotor markers are increasingly discussed to play a key role in the pre-diagnostic phase of Parkinson's disease (PD) the aim of this study was to determine the relation between the risk factors hyperechogenicity of the substantia nigra (SN+) and/or positive family history of PD (faPD+) and putative premotor markers for PD. In a cross-sectional analysis of data of the PRIPS cohort, 1,149 volunteers older than 50 years free of PD were included. In addition to the risk factors SN+ and faPD+, olfactory dysfunction was tested using the Sniffin' sticks test and motor examination was performed.

Reduced but not oxidized cerebrospinal fluid glutathione levels are lowered in Lewy body diseases.

Reduced (GSH(R)) but not oxidized glutathione (GSSG) has been shown to be dramatically altered in the substantia nigra (SN) of Lewy body disease (LBD) patients post mortem; but up to now, there is no convincing evidence that these changes can be monitored in vivo. We investigated GSH(R) and GSSG in rapidly processed cerebrospinal fluid (CSF) and plasma samples of 80 LBD and 35 control subjects and detected reduced CSF GSH(R) levels in LBD subjects. The reduction was negatively associated with age but not with disease-associated parameters.

Transcranial sonography in dystonia.

The cause of idiopathic dystonia is not entirely elucidated. In the pathophysiological model of dystonia, the basal ganglia play a major role, mainly putamen, globus pallidus internus, thalamus, and cortex. However, using conventional structural neuroimaging methods, no specific alterations could be detected in this area.

Early diagnosis of Parkinson's disease.

The accuracy of the clinical diagnosis of Parkinson's disease (PD) is still limited. Especially in the early stages, when cardinal symptoms are not conclusive, diagnosis can be delayed as structural neuroimaging methods such as CCT or MRI do not provide characteristic features that allow the diagnosis of this chronic neurodegenerative disorder. Functional neuroimaging using PET and SPECT techniques is helpful in patients with first signs of parkinsonism, but expensive and not broadly available.

Enlarged hyperechogenic substantia nigra is related to motor performance and olfaction in the elderly.

Enlarged substantia nigra hyperechogenicity (SN+) assessed by transcranial sonography (TCS) may be associated with Parkinson's disease (PD) risk markers such as impaired motor performance and hyposmia. The aim of this multicenter cross-sectional study was to define the association between SN+ and these risk markers in a large population older than 50 years without the diagnosis of PD. In three centers (Tuebingen, Homburg, and Innsbruck), 1,839 individuals were examined.

Place value of transcranial sonography in early diagnosis of Parkinson's disease.

Transcranial B-mode sonography (TCS) is a relatively new method which has been proven to be helpful in the diagnosis of Parkinson's disease (PD). Due to the underlying physical principles, supplementary information to other neuroimaging methods can be derived. Substantia nigra (SN) hyperechogenicity is the characteristic feature of idiopathic PD, which can help in the differentiation of atypical parkinsonian syndromes like multiple system atrophy or progressive supranuclear palsy.

Rivastigmine for the treatment of dementia in patients with progressive supranuclear palsy: Clinical observations as a basis for power calculations and safety analysis.

Cognitive decline and dementia are present in about 50% of patients with progressive supranuclear palsy (PSP). Based on the known involvement of the cholinergic system in PSP patients, and because rivastigmine, in contrast to other cholinesterase inhibitors, inhibits both acetylcholinesterase and butyrylcholinesterase, we discuss clinical observations of five patients suffering from PSP and dementia who were all treated with rivastigmine over a period of 3 to 6 months. We found a slight improvement in specific cognitive function that may justify further controlled studies.

Pre-motor signs of PD are related to SN hyperechogenicity assessed by TCS in an elderly population.

Much effort has been put in the identification of risk factors and pre-motor markers for Parkinson's disease (PD). In contrast to many of the pre-motor markers, SN hyperechogenicity (SN+) assessed by transcranial sonography (TCS) has been found to be conclusive for vulnerability for PD. In two centers in Germany 1204 individuals ≥50 years without the diagnosis of PD were recruited and the prevalence and relation of SN+ to a range of pre-motor markers was evaluated.

Cortical hypometabolism assessed by a metabolic ratio in Parkinson's disease primarily reflects cognitive deterioration-[18F]FDG-PET.

In Parkinson's disease patients with cognitive deterioration, regional cortical hypometabolism has been observed with [(18)F]fluorodeoxyglucose-positron emission tomography (FDG-PET). Our aim was to develop a robust method to subsume the overall degree of metabolic deterioration in Parkinson's disease by means of a single index and to investigate which of the clinical features correlates best with hypometabolism. Twenty-two Parkinson's patients (10 demented) and seven controls underwent FDG-PET.

Sonographic substantia nigra hypoechogenicity in polyneuropathy and restless legs syndrome.

Substantia nigra (SN) hypoechogenicity assessed by transcranial B-mode sonography (TCS) is typical for idiopathic restless legs syndrome (RLS). Here, we investigated whether SN hypoechogenicity may differentiate between polyneuropathy (PNP) patients with and without RLS. Seventy-five patients with PNP, 65 healthy controls, and 75 patients with idiopathic RLS were investigated.