Mild Parkinsonian Signs in the Elderly - Is There an Association with PD? Crossectional Findings in 992 Individuals.

An interesting report from the TREND study - these kinds of study are very important for understanding the prodromal phase of PD and how it compares to normal ageing.

PLoS One. 2014 Mar 27;9(3):e92878. doi: 10.1371/journal.pone.0092878. eCollection 2014.

Lerche S, Hobert M, Brockmann K, Wurster I, Gaenslen A, Hasmann S, Eschweiler GW, Maetzler W, Berg D.

Abstract

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. a stage in which the nigrostriatal system is already affected although to a milder degree than at the time of PD diagnosis, aim of this study was to evaluate the similarities between MPS and PD.

METHODS:

The TREND study is a prospective cross-sectional cohort study in individuals >50 years with biennial assessments designed to identify markers for an earlier diagnosis of Parkinson's and Alzheimer's disease. For this substudy 992 individuals were included for analyses (892 controls, 73 MPS individuals, 27 PD patients). Parameters defining risk of PD (sex, age, positive family history), prodromal markers (hyposmia, REM sleep behavior disorder, depression and autonomic failure) as well as quantitative fine motor, axial motor and cognitive parameters were compared between the three cohorts.

RESULTS:

As expected, PD patients differed from controls with regard to 12 of 15 of the assessed parameters. MPS individuals differed significantly from controls in 12 of the PD-associated parameters, but differed from PD only in 5 parameters.

CONCLUSION:

This study shows that individuals with MPS share many prodromal and clinical markers of PD with PD patients, implying that either a common dynamic process or similar constitutional factors occur in MPS individuals and PD patients.

Risk of accidental injuries amongst Parkinson disease patients

Fractures and head injuries (mainly as a consequence of falls) come out on top of injuries associated with PD.

Eur J Neurol. 2014 Mar 17. doi: 10.1111/ene.12410. [Epub ahead of print]

Wang HC, Lin CC, Lau CI, Chang A, Sung FC, Kao CH.

Abstract

BACKGROUND AND PURPOSE:

To investigate the spectrum and risks of accidental injuries (AIs) amongst Parkinson disease (PD) patients.

METHODS:

The participants comprised PD patients aged 50 years and older who were initially diagnosed between 2000 and 2009, and a comparison group of non-PD patients. The incidence rates of accidental injury types amongst PD and non-PD patients were calculated; hazard ratios were calculated and adjusted for comorbidities, using 95% confidence intervals (CIs) of developing such outcomes in PD patients.

RESULTS:

In total, 4046 PD patients and 16 184 non-PD patients were followed over time. The PD patients demonstrated the following incidence rates and hazard ratios in comparison to the control cohort for accidental injuries: all injuries, 19.78 per 100 person-years (100 PYs), adjusted hazard ratio (HR) 1.30 (95% CI 1.24-1.36); head injury, 2.95 per 100 PYs, HR 1.88 (95% CI 1.64-2.15); bone fracture and dislocation, 4.61 per 100 PYs, HR 1.39 (95% CI 1.25-1.54); burns, 0.66 per 100 PYs, HR 1.01 (95% CI 0.78-1.32); injury to spinal cord, plexus and nerves, 0.15 per 100 PYs, HR 1.25 (95% CI 0.72-2.17); superficial injuries and contusions, 11.41 per 100 PYs, HR 1.20 (95% CI 1.12-1.27). The injury risk for the 69-79 years age group in PD compared with controls of the same age (HR 1.38) was significantly higher compared with that of the 50-69 age groups in PD and controls (HR 1.16).

CONCLUSIONS:

Parkinson disease patients demonstrate a significantly elevated risk of developing all accidental injury types except burn injuries and injuries to spinal cord, plexus and nerves, compared with age-matched controls. The risk increases as age increases.

Reluctance to start medication for Parkinson's disease: A mutual misunderstanding by patients and physicians.

This is really interesting and an important issue to understand more fully. I too would have expected patients to be more reluctant about starting levodopa rather than dopamine agonists.

Parkinsonism Relat Disord. 2014 Mar 12. pii: S1353-8020(14)00083-2. doi: 10.1016/j.parkreldis.2014.03.001. [Epub ahead of print]

Mestre TA, Teodoro T, Reginold W, Graf J, Kasten M, Sale J, Zurowski M, Miyasaki J, Ferreira JJ, Marras C.

Abstract

Reluctance to start medication has never been investigated before in PD. We studied reluctance to start medication for PD motor symptoms, namely its prevalence, underlying reasons, drug-specificity, and associated delay in the start of PD medication. A cross-sectional observational international study was conducted. Patients with a clinical diagnosis of PD advised to start antiparkinsonian medication in the previous 5 years were invited to complete a questionnaire in three centers located in North America and Europe. An electronic online survey was sent to physicians through the mailing list of the Movement Disorder Society. 469 participants (201 PD patients, 268 physicians). 40.2% (n = 82) of the patients reported reluctance to start medication, but 88.6% (n = 234/264) of the physicians estimated that ≤20% of their patients with PD had been reluctant to start medication. The most common reasons reported by patients were the fear of side effects (n = 35, 55.6%), followed by non-acceptance of diagnosis (n = 23, 36.5%); fear of a temporally limited benefit was more commonly selected by physicians (n = 92/267, 34.5%). Patients indicated reluctance to start DAs more frequently compared with L-DOPA (OR: 2.22, 95% CI: 1.30, 9.03; p = 0.013) while physicians perceived L-DOPA to be associated with more reluctance (OR: 4.7, 95% CI: 3.41; 6.59; p < 0.0001). Patients with PD and physicians have a different perspective on the issue of reluctance to start medication. There is a need to bring physicians and patients with PD closer to a shared vision of the problem reluctance to start medication.

Reduced risk of Parkinson's disease associated with lower body mass index and heavy leisure-time physical activity

This is similar to what has been found previously in epidemiological studies looking at BMI and other measures of obesity preceding PD. It is the tendency that after diagnosis people tend to lose weight. Regarding physical activity, it is always difficult to know whether the subjects that had reduced physical activity pre-morbidly where not simply in an early phase of the disease.

Eur J Epidemiol. 2014 Mar 16. [Epub ahead of print]

Sääksjärvi K, Knekt P, Männistö S, Lyytinen J, Jääskeläinen T, Kanerva N, Heliövaara M.

Abstract

The risk factors for Parkinson's disease (PD) are not well established. We therefore examined the prediction of various lifestyle factors on the incidence of PD in a cohort drawn from the Finnish Mobile Clinic Health Examination Survey, conducted in 1973-1976. The study population comprised 6,715 men and women aged 50-79 years and free of PD at the baseline. All of the subjects completed a baseline health examination (including height and weight measurements) and a questionnaire providing information on leisure-time physical activity, smoking, and alcohol consumption. During a 22-year follow-up, 101 incident cases of PD occurred. The statistical analyses were based on Cox's model including age, sex, education, community density, occupation, coffee consumption, body mass index (BMI), leisure-time physical activity, smoking and alcohol consumption as independent variables. At first, BMI was not associated with PD risk, but after exclusion of the first 15 years of follow-up, an elevated risk appeared at higher BMI levels (P for trend 0.02). Furthermore, subjects with heavy leisure-time physical activity had a lower PD risk than those with no activity [relative risk (RR) 0.27, 95 % confidence interval (CI) 0.08-0.90]. In variance with findings for other chronic diseases, current smokers had a lower PD risk than those who had never smoked (RR 0.23, 95 % CI 0.08-0.67), and individuals with moderate alcohol intake (at the level of <5 g/day) had an elevated PD risk compared to non-drinkers. The results support the hypothesis that lifestyle factors predict the occurrence of Parkinson's disease, but more research is needed.

Skin nerve α-synuclein deposits: A biomarker for idiopathic Parkinson disease

Neurology. 2014 Mar 14. [Epub ahead of print]

Donadio V, Incensi A, Leta V, Giannoccaro MP, Scaglione C, Martinelli P, Capellari S, Avoni P, Baruzzi A, Liguori R.

Author information

From the IRCCS Istituto delle Scienze Neurologiche (V.D., A.I., V.L., M.P.G., C.S., S.C., P.A., A.B., R.L.), Bologna; and Dipartimento di Scienze Biomediche e Neuromotorie (V.L., M.P.G., P.M., S.C., P.A., R.L.), Università di Bologna, Italy.

Abstract

OBJECTIVE:

To investigate (1) whether phosphorylated α-synuclein deposits in skin nerve fibers might represent a useful biomarker for idiopathic Parkinson disease (IPD), and (2) the underlying pathogenesis of peripheral neuropathy associated with IPD.

METHODS:

Twenty-one well-characterized patients with IPD were studied together with 20 patients with parkinsonisms assumed not to have α-synuclein deposits (PAR; 10 patients fulfilling clinical criteria for vascular parkinsonism, 6 for tauopathies, and 4 with parkin mutations) and 30 controls. Subjects underwent nerve conduction velocities from the leg to evaluate large nerve fibers and skin biopsy from proximal (i.e., cervical) and distal (i.e., thigh and distal leg) sites to study small nerve fibers and deposits of phosphorylated α-synuclein considered the pathologic form of α-synuclein.

RESULTS:

Patients with IPD showed a small nerve fiber neuropathy prevalent in the leg with preserved large nerve fibers. PAR patients showed normal large and small nerve fibers. Phosphorylated α-synuclein was not found in any skin sample in PAR patients and controls, but it was found in all patients with IPD in the cervical skin site. Abnormal deposits were correlated with leg epidermal denervation.

CONCLUSIONS:

The search for phosphorylated α-synuclein in proximal peripheral nerves is a sensitive biomarker for IPD diagnosis, helping to differentiate IPD from other parkinsonisms. Neuritic inclusions of α-synuclein were correlated with a small-fiber neuropathy, suggesting their direct role in peripheral nerve fiber damage.

CLASSIFICATION OF EVIDENCE:

This study provides Class III evidence that the presence of phosphorylated α-synuclein in skin nerve fibers on skin biopsy accurately distinguishes IPD from other forms of parkinsonism.

Symptomatic efficacy of rasagiline monotherapy in early Parkinson's disease: Post-hoc analyses from the ADAGIO trial

Parkinsonism Relat Disord. 2014 Mar 5. pii: S1353-8020(14)00077-7. doi: 10.1016/j.parkreldis.2014.02.024. [Epub ahead of print]

Jankovic J, Berkovich E, Eyal E, Tolosa E.

Abstract

BACKGROUND:

The ADAGIO study included a large cohort of patients with early PD (baseline total-UPDRS = 20) who were initially randomized to rasagiline and placebo, thereby allowing analyses of symptomatic efficacy.

METHODS:

Post-hoc analyses comparing the efficacy of rasagiline 1 mg/day (n = 288) versus placebo (n = 588) on key symptoms at 36 weeks, and on total-UPDRS scores over 72 weeks (completer population: rasagiline 1 mg/day n = 221, placebo n = 392) were performed.

RESULTS:

Treatment with rasagiline resulted in significantly better tremor, bradykinesia, rigidity and postural-instability-gait-difficulty scores at week 36 versus placebo. Whereas the placebo group experienced progressive deterioration from baseline (2.6 UPDRS points at week 36), patients in the rasagiline group were maintained at baseline values at week 60 (UPDRS-change of 0.3 points). At week 72, patients who had received continuous monotherapy with rasagiline experienced a worsening of only 1.6 points.

CONCLUSIONS:

Treatment with rasagiline maintained motor function to baseline values for at least a year with significant benefits observed in all key PD motor symptoms.

A Randomized Study of Rotigotine Dose Response on 'Off' Time in Advanced Parkinson's Disease.

J Parkinsons Dis. 2014 Mar 18. [Epub ahead of print]

Nicholas AP, Borgohain R, Chaná P, Surmann E, Thompson EL, Bauer L, Whitesides J, Elmer LW

Abstract

Background: Previous phase III studies in patients with advanced Parkinson's disease (PD) not adequately controlled on levodopa demonstrated significant reduction of 'off' time with rotigotine transdermal system up to 16 mg/24 h. However, the minimal effective dose has not been established. Objective: This international, randomized, double-blind, placebo-controlled study (SP921; NCT00522379) investigated rotigotine dose response up to 8 mg/24 h. Methods: Patients with advanced idiopathic PD (≥2.5 h of daily 'off' time on stable doses of levodopa) were randomized 1 : 1:1 : 1:1 to receive rotigotine 2, 4, 6, or 8 mg/24 h or placebo, titrated over 4 weeks and maintained for 12 weeks. The primary efficacy variable was change from baseline to end of maintenance in absolute time spent 'off'. Results: 409/514 (80%) randomized patients completed maintenance. Mean (± SD) baseline daily 'off' times (h/day) were placebo: 6.4 (± 2.5), rotigotine 2-8 mg/24 h: 6.4 (± 2.6). Rotigotine 8 mg/24 h was the minimal dose to significantly reduce 'off' time versus placebo. LS mean (± SE) absolute change in daily 'off' time (h/day) from baseline was -2.4 (± 0.28) with rotigotine 8 mg/24 h, and -1.5 (± 0.26) with placebo; absolute change in 'off' time in the 8 mg/24 h group compared with placebo was -0.85 h/day (95% CI -1.59, -0.11; p = 0.024). There was an apparent dose-dependent trend. Adverse events (AEs) reported at a higher incidence in the rotigotine 8 mg/24 h group versus placebo included application site reactions, nausea, dry mouth, and dyskinesia; there was no worsening of insomnia, somnolence, orthostatic hypotension, confusional state or hallucinations, even in patients ≥75 years of age. Conclusions: The minimal statistically significant effective dose of rotigotine to reduce absolute 'off' time was 8 mg/24 h. The AE profile was similar to previous studies.

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

Exciting to see early data reported from this important study of PD risk.

Eur J Neurol. 2014 Feb 24. doi: 10.1111/ene.12382. [Epub ahead of print]

Gaenslen A, Wurster I, Brockmann K, Huber H, Godau J, Faust B, Lerche S, Eschweiler GW, Maetzler W, Berg D.

Abstract

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.

METHODS:

From the Tübinger Evaluation of Risk Factors for Early Detection of Neurodegeneration (TREND) study, 698 healthy individuals aged 50-80 years reporting one or more of the selected prodromal markers (SPMs), but without neurodegenerative disorders, were evaluated and classified according to the status of prodromal markers. Other prodromal PD-related features were assessed with a 23-item questionnaire and compared between participants with and without the three SPMs.

RESULTS:

Individuals with the SPMs for PD endorsed more of the additional possible prodromal features of PD than those without; of 23 possible prodromal features, the median number identified amongst participants with no SPMs was two, compared with four with one marker, five with two and seven with three (P < 0.001). Regarding individual SPMs, participants with depression and RBD endorsed five of 23 markers, compared with three for those with hyposmia (P = 0.001). There was no significant increase in the number of prodromal features amongst those with two SPMs compared with those with only one marker.

CONCLUSIONS:

Individuals with the SPMs for PD report a higher prevalence of other prodromal PD symptoms. This may indicate that these markers can identify individuals at risk for PD.

Cerebrospinal Fluid α-Synuclein Predicts Cognitive Decline in Parkinson's Disease Progression in the DATATOP Cohort

The importance of identifying biomarkers for PD cannot be overstated. 

Very interesting to see how CSF alpha-syn was related to cognitive parameters but important additional findings were 1) the decrease in alpha-syn over 2 years of early disease progression, which may have important implications for study in the premotor phase. However, 2) failure to find a relationship with motor severity rating scales, a finding which the authors spend some time considering.

Am J Pathol. 2014 Feb 27. pii: S0002-9440(14)00012-1. doi: 10.1016/j.ajpath.2013.12.007. [Epub ahead of print]

Stewart T, Liu C, Ginghina C, Cain KC, Auinger P, Cholerton B, Shi M, Zhang J; the Parkinson Study Group DATATOP Investigators.

Abstract

Most patients with Parkinson's disease (PD) develop both cognitive and motor impairment, and biomarkers for progression are urgently needed. Although α-synuclein is altered in cerebrospinal fluid of patients with PD, it is not known whether it predicts motor or cognitive deterioration. We examined clinical data and α-synuclein in >300 unmedicated patients with PD who participated in the deprenyl and tocopherol antioxidative therapy of parkinsonism (DATATOP) study, with up to 8 years of follow-up. Longitudinal measures of motor and cognitive function were studied before (phase 1) and during (phase 2) levodopa therapy; cerebrospinal fluid was collected at the beginning of each phase. Correlations and linear mixed models were used to assess α-synuclein association with disease severity and prediction of progression in the subsequent follow-up period. Despite decreasing α-synuclein (phase 1 to phase 2 change of -0.05 ± 0.21 log-transformed values, P < 0.001), no correlations were observed between α-synuclein and motor symptoms. Longitudinally, lower α-synuclein predicted better preservation of cognitive function by several measures [Selective Reminding Test total recall α-synuclein × time interaction effect coefficient, -0.12 (P = 0.037); delayed recall, -0.05 (P = 0.002); New Dot Test, -0.03 (P = 0.002)]. Thus, α-synuclein, although not clinically useful for motor progression, might predict cognitive decline, and future longitudinal studies should include this outcome for further validation.

Bone health in Parkinson's disease: a systematic review and meta-analysis

DEXA Bone Scan

In this large piece of work we have gathered the best quality studies in the literature to understand more about bone health and fracture risk in PD. We see that patients with Parkinson's have much poorer bone health than healthy people of the same age. The reasons why are likely multi-factorial and are also covered in this paper, and all of this is important because people with Parkinson's also have a greater risk of falls. Watch out for more of our work on bone health in Parkinson's on this blog!

J Neurol Neurosurg Psychiatry. 2014 Mar 11. doi: 10.1136/jnnp-2013-307307. [Epub ahead of print] Torsney KM, Noyce AJ, Doherty KM, Bestwick JP, Dobson R, Lees AJ.

OBJECTIVE: Parkinson's disease (PD) and osteoporosis are chronic diseases associated with increasing age. Single studies have reported associations between them and the major consequence, namely, increased risk of fractures. The aim of this systematic review and meta-analysis was to evaluate the relationship of PD with osteoporosis, bone mineral density (BMD) and fracture risk.

METHODS:

A literature search was undertaken on 4 September 2012 using multiple indexing databases and relevant search terms. Articles were screened for suitability and data extracted where studies met inclusion criteria and were of sufficient quality. Data were combined using standard meta-analysis methods.

RESULTS:

23 studies were used in the final analysis. PD patients were at higher risk of osteoporosis (OR 2.61; 95% CI 1.69 to 4.03) compared with healthy controls. Male patients had a lower risk for osteoporosis and osteopenia than female patients (OR 0.45; 95% CI 0.29 to 0.68). PD patients had lower hip, lumbar spine and femoral neck BMD levels compared with healthy controls; mean difference, -0.08, 95% CI -0.13 to -0.02 for femoral neck; -0.09, 95% CI -0.15 to -0.03 for lumbar spine; and -0.05, 95% CI -0.07 to -0.03 for total hip. PD patients were also at increased risk of fractures (OR 2.28; 95% CI 1.83 to 2.83).

CONCLUSIONS:

This systematic review and meta-analysis demonstrate that PD patients are at higher risk for both osteoporosis and osteopenia compared with healthy controls, and that female patients are at greater risk than male patients. Patients with PD also have lower BMD and are at increased risk of fractures.

Transcranial sonography and [18 F]fluorodeoxyglucose positron emission tomography for the differential diagnosis of parkinsonism: a head-to-head comparison

Strong support for transcranial sonography in this paper. I must say my own experience performing TCS to date has been a positive one. The merits are clear to see and if atypical PD can be distinguished from idiopathic PD that would be a huge bonus! Alastair Noyce

Eur J Neurol. 2014 Mar 6. doi: 10.1111/ene.12394. [Epub ahead of print]

Hellwig S, Reinhard M, Amtage F, Guschlbauer B, Buchert R, Tüscher O, Weiller C, Niesen WD, Meyer PT.

Author information

Department of Neurology, University Hospital Freiburg, Freiburg, Germany; Department of Psychiatry and Psychotherapy, University Hospital Freiburg, Freiburg, Germany.

Abstract

BACKGROUND AND PURPOSE:

Brain imaging with positron emission tomography using [18 F]fluorodeoxyglucose (FDG-PET) and transcranial B-mode sonography (TCS) improves the differential diagnosis of parkinsonism. The diagnostic merits of these approaches in identifying and differentiating atypical parkinsonian syndromes (APS) are compared.

METHODS:

Data were included from 36 patients with clinically suspected APS who underwent PET and TCS. FDG-PET scans were analyzed by visual assessment (including voxel-based statistical maps) of a priori defined disease-specific metabolic patterns. Sonographers achieved diagnoses according to pre-defined criteria for echogenicities of the substantia nigra and lenticular nucleus, and third ventricle diameter. Patients with APS were identified and allocated to the subgroups multiple system atrophy (MSA), progressive supranuclear palsy (PSP) or corticobasal degeneration (CBD).

RESULTS:

After a median follow-up period of 9 months, the final clinical diagnoses (reference standard) were Parkinson's disease, n = 15; MSA, n = 9; PSP, n = 7; and CBD, n = 5 (n = 21 APS in total). Six patients (4 APS) showed an insufficient bone window for TCS. In the remaining 30 patients, sensitivity/specificity for diagnosing APS were 82%/100% and 82%/85% for FDG-PET and TCS, respectively. Diagnostic accuracies did not differ between FDG-PET (90%) and TCS (83%; P = 0.69). Likewise, overall accuracy of subgroup classification (non-APS, MSA, PSP and CBD) did not differ between modalities (FDG-PET 87% and TCS 83%; P = 1.00).

CONCLUSIONS:

FDG-PET and TCS show comparable accuracies for differential diagnosis of neurodegenerative parkinsonism. This preliminary study supports the use of TCS and warrants further prospective validation.

MR Imaging of the Substantia Nigra at 7 T Enables Diagnosis of Parkinson Disease

A potential role of MRI in PD is growing. This interesting paper demonstrates structural changes and signal changes that differentiated PD patients from healthy controls. Obviously it would be useful to replicate this in a larger number of subjects and study the appearances of patients with atypical parkinsonian disorders too. But as well as playing a possible role in diagnosis, it may have a role in early detection, perhaps even in the pre-diagnostic phase. Furthermore it may help us understand some the abnormalities seen with other imaging modalities such as transcranial sonography - Alastair Noyce

Radiology. 2014 Feb 26:131448. [Epub ahead of print]

Cosottini M, Frosini D, Pesaresi I, Costagli M, Biagi L, Ceravolo R, Bonuccelli U, Tosetti M.

Author information

From the IMAGO7 Foundation, Pisa, Italy (M. Cosottini, M. Costagli); Department of Translational Research and New Surgical and Medical Technologies (M. Cosottini) and Neurology Unit, Department of Clinical and Experimental Medicine (D.F., R.C., U.B.), University of Pisa, Pisa, Italy; Neuroradiology Unit, Department of Diagnostic and Interventional Radiology, Azienda Ospedaliero-Universitaria Pisana (AOUP), Pisa, Italy (I.P.); and Stella Maris Scientific Institute, Pisa, Italy (L.B., M.T.).

Abstract

Purpose To evaluate the anatomy of the substantia nigra (SN) in healthy subjects by performing 7-T magnetic resonance (MR) imaging of the SN, and to prospectively define the accuracy of 7-T MR imaging in distinguishing Parkinson disease (PD) patients from healthy subjects on an individual basis. Materials and Methods The 7-T MR imaging protocol was approved by the Italian Ministry of Health and by the local competent ethics committee. SN anatomy was described ex vivo on a gross brain specimen by using highly resolved proton-density (spin-echo proton density) and gradient-recalled-echo (GRE) images, and in vivo in eight healthy subjects (mean age, 40.1 years) by using GRE three-dimensional multiecho susceptibility-weighted images. After training on appearance of SN in eight healthy subjects, the SN anatomy was evaluated twice by two blinded observers in 13 healthy subjects (mean age, 54.7 years) and in 17 PD patients (mean age, 56.9 years). Deviations from normal SN appearance were described and indicated as abnormal, and both diagnostic accuracy and intra- and interobserver agreement for diagnosis of PD with 7-T MR imaging were calculated. Results Three-dimensional multiecho susceptibility-weighted 7-T MR imaging reveals a three-layered organization of the SN allowing readers to distinguish pars compacta ventralis and dorsalis from pars reticulata. The abnormal architecture of the SN allowed a discrimination between PD patients and healthy subjects with sensitivity and specificity of 100% and 96.2% (range, 92.3%-100%), respectively. Intraobserver agreement (κ = 1) and interobserver agreement (κ = 0.932) were excellent. Conclusion MR imaging at 7-T allows a precise characterization of the SN and visualization of its inner organization. Three-dimensional multiecho susceptibility-weighted images can be used to accurately differentiate healthy subjects from PD patients, which provides a novel diagnostic opportunity.

Problematic Internet use in Parkinson's disease.

Parkinsonism Relat Disord. 2014 Feb 5. pii: S1353-8020(14)00035-2. doi: 10.1016/j.parkreldis.2014.01.019. [Epub ahead of print]

Wu K, Politis M, O'Sullivan SS, Lawrence AD, Warsi S, Lees A, Piccini P.

Abstract

BACKGROUND:

Problematic Internet use (PIU) has been associated with impulse control disorders (ICDs), and postulated to share characteristics of a behavioral addiction with both impulsive and compulsive features. However, Internet use has not been previously systematically studied in Parkinson's disease.

AIM:

We explore Internet use in PD patients with and without ICDs and matched healthy controls. We hypothesize that the PD-ICD patients will spend more time on the Internet, accessing websites related to their ICDs, compared with PD patients without ICDs and healthy volunteers.

METHODS:

Our study is the first to systematically explore problematic Internet use in patients with PD, with and without ICDs. Twenty-nine PD patients with ICDs, twenty PD patients without ICDs and nineteen healthy controls were recruited. All participants endorsed using the Internet for non-essential purposes. They underwent a semi-structured interview and completed questionnaires including the Yale-Brown Obsessive Compulsive Scale adapted for Internet use (Y-BOCS-Internet).

RESULTS:

PD-ICD patients scored significantly higher on the Y-BOCS-Internet than the PD-control and HV groups (PD-ICD: 13.69; PD-control: 5.42; HV: 4.70; p < 0.0001). Compared to PD controls and HV groups, the PD-ICD group spent more time on the Internet (p = 0.0001), described significantly more effort to resist Internet use (p = 0.0002), thoughts about Internet use (p < 0.0001) and its interference with their life functioning (p = 0.0025).

DISCUSSION:

Our results suggest that PD patients with ICDs have a relative increased tendency towards excessive Internet use compared to those without ICDs and healthy controls. Clinicians should actively screen for excessive Internet use in patients with ICDs.

Neurodegenerative Disorder Risk in Idiopathic REM Sleep Behavior Disorder: Study in 174 Patients

Further support for RBD as a powerful risk factor

PLoS One. 2014 Feb 26;9(2):e89741. doi: 10.1371/journal.pone.0089741. eCollection 2014.

Iranzo A, Fernández-Arcos A, Tolosa E, Serradell M, Molinuevo JL, Valldeoriola F, Gelpi E, Vilaseca I, Sánchez-Valle R, Lladó A, Gaig C, Santamaría J.

Author information

Neurology Service, Hospital Clínic de Barcelona, IDIBAPS, Barcelona, Spain ; CIBERNED, Barcelona, Spain.

Neurology Service, Hospital Clínic de Barcelona, IDIBAPS, Barcelona, Spain.

Neurological Tissue Bank, Biobanc-Hospital Clinic, IDIBAPS, Barcelona, Spain.

Otorhinolaryngology Service, Hospital Clínic de Barcelona, CIBER Enfermedades Respiratorias, Bunyola, Spain.

Abstract

OBJECTIVE:

To estimate the risk for developing a defined neurodegenerative syndrome in a large cohort of idiopathic REM sleep behavior disorder (IRBD) patients with long follow-up.

METHODS:

Using the Kaplan-Meier method, we estimated the disease-free survival rate from defined neurodegenerative syndromes in all the consecutive IRBD patients diagnosed and followed-up in our tertiary referral sleep center between November 1991 and July 2013.

RESULTS:

The cohort comprises 174 patients with a median age at diagnosis of IRBD of 69 years and a median follow-up of four years. The risk of a defined neurodegenerative syndrome from the time of IRBD diagnosis was 33.1% at five years, 75.7% at ten years, and 90.9% at 14 years. The median conversion time was 7.5 years. Emerging diagnoses (37.4%) were dementia with Lewy bodies (DLB) in 29 subjects, Parkinson disease (PD) in 22, multiple system atrophy (MSA) in two, and mild cognitive impairment (MCI) in 12. In six cases, in whom postmortem was performed, neuropathological examination disclosed neuronal loss and widespread Lewy-type pathology in the brain in each case.

CONCLUSIONS:

In a large IRBD cohort diagnosed in a tertiary referral sleep center, prolonged follow-up indicated that the majority of patients are eventually diagnosed with the synucleinopathies PD, DLB and less frequently MSA. IRBD represented the prodromal period of these conditions. Our findings in IRBD have important implications in clinical practice, in the investigation of the early pathological events occurring in the synucleinopathies, and for the design of interventions with potential disease-modifying agents.

Parkinsonism in elderly rheumatoid arthritis patients.

Interesting, but too small numbers currently. Needs replicating in a larger group.

Clin Ter. 2014 Jan-Feb;165(1):19-21. doi: 10.7471/CT.2014.1655.

Bes C, Altunrende B, Yılmaz Türkoğlu S, Yıldız N, Soy M.

Author information

Department of Rheumatology Bakırköy Dr. Sadi Konuk Training and Research Hospital, İstanbul.

Department of Neurology, The Hospital of University of Abant Izzet Baysal, Bolu.

Department of Rheumatology, Hisar Intercontinental Hospital, İstanbul, Turkey.

Abstract

OBJECTIVE:

The incidences of extrapyramidal symptoms and Parkinson's disease were reported to be increased in patients with rheumatoid arthritis (RA). In this study we aimed to explore the frequency of the symptoms of Parkinsonism among RA patients older than 60 years.

PATIENTS AND METHODS:

30 (6 males, 24 females) consecutive RA patients, followed at a rheumatology outpatient clinic, who were 60 years of age or older; 23 patients who were diagnosed as PD and 50 sex and age matched healthy controls were included to the study. All participants were examined for the motor and non-motor findings of Parkinsonism including bradykinesia, rigidity, tremor, postural abnormality, upper limb sway abnormality, gait impairment, decrease in facial expression, seborrhea, slowing of speech and impairment in the self care.

RESULTS:

When the RA, PD cases and healthy control group were compared for bradykinesia, rigidity, tremor, posture, upper limb sway, gait impairment, facial expression, seborrhea, speech and self care; highly significant differences were seen for all parameters. Two out of the 30 RA cases (6,7%) were diagnosed as Parkinson's disease.

CONCLUSIONS:

The signs of Parkinsonism and Parkinson's disease were found more frequent in elderly RA cases as compared to healthy controls.

Alcohol intake and risk of Parkinson's disease: A meta-analysis of observational studies

Similar to our meta-analysis findings

Mov Disord. 2014 Mar 3. doi: 10.1002/mds.25863. [Epub ahead of print]

Zhang D, Jiang H, Xie J.

Author information

Department of Epidemiology and Health Statistics, Qingdao University Medical College, Qingdao, P.R. China.

Abstract

BACKGROUND:

The association of alcohol intake with risk of Parkinson's disease remains unclear.

METHODS:

Pertinent studies were identified in PubMed and EMBASE. The fixed-effect or random-effect model was selected based on heterogeneity. The dose-response relationship was assessed by restricted cubic splines.

RESULTS:

We included 32 articles, involving 677,550 subjects (9994 cases). The smoking-adjusted risk of Parkinson's disease for the highest versus lowest level of alcohol intake was relative risk (RR) 0.78 (95% confidence interval [CI], 0.67-0.92) overall, 0.86 (95% CI, 0.75-0.995) in prospective studies, and 0.74 (95% CI, 0.58-0.96) in matched case-control studies. A significant association was found with beer (0.59; 95% CI, 0.39-0.90) but not with wine and liquor, and for males (0.65; 95% CI, 0.47-0.90) after a sensitivity analysis but not for females. The risk of Parkinson's disease decreased by 5% (0.95; 95% CI, 0.89-1.02) for every 1 drink/day increment in alcohol intake in a linear (Pfor nonlinearity  = 0.85) dose-response manner.

CONCLUSIONS:

Alcohol intake, especially beer, might be inversely associated with risk of Parkinson's disease © 2014 International Parkinson and Movement Disorder Society.

The influences of age on olfaction: a review

Front Psychol. 2014 Feb 7;5:20. eCollection 2014.

Doty RL, Kamath V.

Abstract

Decreased olfactory function is very common in the older population, being present in over half of those between the ages of 65 and 80 years and in over three quarters of those over the age of 80 years. Such dysfunction significantly influences physical well-being and quality of life, nutrition, the enjoyment of food, as well as everyday safety. Indeed a disproportionate number of the elderly die in accident gas poisonings each year. As described in this review, multiple factors contribute to such age-related loss, including altered nasal engorgement, increased propensity for nasal disease, cumulative damage to the olfactory epithelium from viral and other environmental insults, decrements in mucosal metabolizing enzymes, ossification of cribriform plate foramina, loss of selectivity of receptor cells to odorants, changes in neurotransmitter and neuromodulator systems, and neuronal expression of aberrant proteins associated with neurodegenerative disease. It is now well established that decreased smell loss can be an early sign of such neurodegenerative diseases as Alzheimer's disease and sporadic Parkinson's disease. In this review we provide an overview of the anatomy and physiology of the aging olfactory system, how this system is clinically evaluated, and the multiple pathophysiological factors that are associated with its dysfunction.