Thursday, 22 March 2012

The effect of Alzheimer's disease and Parkinson's disease on olfaction: A meta-analysis.

Behav Brain Res. 2012 Mar 5. [Epub ahead of print]
Rahayel S, Frasnelli J, Joubert S.


Centre de Recherche en Neuropsychologie et Cognition (CERNEC) Département de Psychologie, Université de Montréal, CP 6128, Succursale Centre-Ville, Montréal, Québec, H3C 3J7, Canada; Département de Psychologie, Université du Québec à Montréal, CP 8888, Succursale Centre-Ville, Montréal, Québec, H3C 3P8, Canada.


Impaired sense of smell is one of the earliest clinical features in both Alzheimer's disease (AD) and Parkinson's disease (PD). A meta-analysis was performed on articles obtained from the PubMed database in order to determine what aspects of olfaction are affected in these two diseases. By applying strict criteria, we included a total of 81 studies. Included articles respected the following criteria: (1) patients had a clinical diagnosis of AD or PD; (2) patients were compared to a healthy control group; (3) patients and controls were age-matched; (4) olfactory function was assessed by means of a psychophysical olfactory test; (5) mean and standard deviation were reported. Results indicate that AD and PD patients are more impaired on odor identification and recognition tasks than on odor detection thresholds task. In addition, PD patients are more impaired on detection thresholds than AD patients. These results suggest that PD patients are more impaired on low-level perceptual olfactory tasks whereas AD patients are more strongly impaired on higher-order olfactory tasks involving specific cognitive processes. The effect appears more pronounced for AD than PD, which appears to be affected more homogeneously. In conclusion, olfactory identification and recognition appear as the most interesting candidates to be included in a battery to detect subclinical cases in AD. In parallel, detection thresholds should be included in such a battery for subclinical PD patients.

Effects of dopamine on sensitivity to social bias in Parkinson's disease.

PLoS One. 2012;7(3):e32889. Epub 2012 Mar 9.
Djamshidian A, O'Sullivan SS, Lees A, Averbeck BB.


Department of Molecular Neuroscience and Reta Lila Weston Institute for Neurological Studies, University College London (UCL), London, United Kingdom.


Patients with Parkinson's disease (PD) sometimes develop impulsive compulsive behaviours (ICBs) due to their dopaminergic medication. We compared 26 impulsive and 27 non-impulsive patients with PD, both on and off medication, on a task that examined emotion bias in decision making. No group differences were detected, but patients on medication were less biased by emotions than patients off medication and the strongest effects were seen in patients with ICBs. PD patients with ICBs on medication also showed more learning from negative feedback and less from positive feedback, whereas off medication they showed the opposite effect.

Risk of Parkinson Disease Onset in Patients With Diabetes: A 9-year population-based cohort study with age and sex stratifications.

Diabetes Care. 2012 Mar 19. [Epub ahead of print]
Sun Y, Chang YH, Chen HF, Su YH, Su HF, Li CY.


Department of Neurology, En Chu Kong Hospital, Sanxia District, New Taipei City, Taiwan.


We retrospectively assessed the age- and sex-specific incidence and relative risk of Parkinson disease (PD) in Taiwan's diabetic population.

Study cohort included 603,416 diabetic patients and 472,188 nondiabetic control subjects. Incidence rate and relative risk of PD (ICD-9-CM 332.0) were evaluated.

The incidence of PD was 3.59 and 2.15 per 10,000 person-years for the diabetic and control group, respectively, representing a covariate adjusted hazard ratio (HR) of 1.61 (95% CI 1.56-1.66), which was substantially reduced to 1.37 (1.32-1.41) after adjusting for medical visits. Diabetes was associated with a significantly elevated risk of PD in all sex and age stratifications except in young women, with the highest HR noted for young men aged 21-40 years (2.10 [1.01-4.42]), followed by women aged 41-60 (2.05 [1.82-2.30]) and >60 years (1.65 [1.58-1.73]).

Diabetes is associated with an increased risk of PD onset in a Chinese population, and the relation is stronger in women and younger patients.

Tuesday, 13 March 2012

Prevalence and Profile of Mild Cognitive Impairment in Parkinson's Disease.

Neurodegener Dis. 2012 Mar 6. [Epub ahead of print]
Monastero R, Di Fiore P, Ventimiglia GD, Ventimiglia CC, Battaglini I, Camarda R, Camarda C.


Laboratory of Epidemiology and Psychology of Aging and Dementia (LEPAD), Department of Experimental Biomedicine and Clinical Neuroscience (BioNeC), University of Palermo, Palermo, Italy.


Background/Aims: The frequency of mild cognitive impairment (MCI) in Parkinson's disease (PD) ranges from 19 to 40%, and this is probably due to methodological differences between the studies. The aim of this study was to evaluate the frequency and profile of MCI in a large sample of nondemented PD subjects and neurologically healthy subjects (NHS). Methods: A total of 872 subjects (582 controls and 290 PD) were included. The association between MCI and PD was tested, using logistic regression models; odds ratios (OR) with 95% confidence intervals (CI) were calculated. Results: Fifty-three percent of PD subjects and 45% NHS met the criteria for MCI (p = 0.001). The PD subjects showed a higher frequency of nonamnestic MCI (naMCI), compared to NHS (23.8 vs. 14.4%, p ≤ 0.0001). In comparison to NHS, PD was associated with a univariate OR of 1.9 (95% CI = 1.3-2.8) for naMCI, and this association was marginally significant after multiple comparisons (multivariate OR = 1.5, 95% CI = 0.96-2.3, p = 0.077). Conclusion: The association between PD and the impairment of nonmemory domains is probably due to frontal-subcortical involvement, which characterizes the disease.

Deterioration of Parkinson's disease during hospitalization: survey of 684 patients.

BMC Neurol. 2012 Mar 8;12(1):13. [Epub ahead of print]
Gerlach OH, Broen MP, van Domburg PH, Vermeij AJ, Weber WE.



A substantial fraction of Parkinson's disease patients deteriorate during hospitalisation, but the precise proportion and the reasons why have not been studied systematically and the focus has been on surgical wards and on Accident & Emergency departments. We assessed the prevalence and risk factors of deterioration of Parkinson's disease symptoms during hospitalization, including all wards.


We invited Parkinson's disease patients from three neurology departments in The Netherlands to answer a standardised questionnaire on general, disease and hospital related issues. Patients who had been hospitalized in the previous year were included and analysed. Possible risk factors for Parkinson's disease deterioration were identified. Proportions were analysed using the Chi-Square test and a logistic regression analysis was performed.


Eighteen percent of 684 Parkinson's disease patients had been hospitalized at least once in the last year. Twenty-one percent experienced deterioration of motor symptoms, 33% did have one or more complications and 26% had received incorrect anti-Parkinson's medication. There were no statistically significant differences for these variables between admissions on neurologic or non-neurologic wards and between having surgery or not. Incorrect medication during hospitalization was significantly associated with higher risk (OR 5.8, CI 2.5-13.7) of deterioration, as were having infections (OR 6.7 CI 1.8-24.7). A higher levodopa equivalent dose per day was a significant risk factor for deterioration. When adjusting for different variables, wrong medication distribution was the most important risk factor for deterioration.


Incorrect medication and infections are the important risk factors for deterioration of Parkinson's disease patients both for admissions with and without surgery and both for admissions on neurologic and non-neurologic wards. Measures should be taken to improve care and incorporated in guidelines.

Thursday, 8 March 2012

Pharmacist's role in a Parkinson's disease and movement disorders clinic.

Am J Health Syst Pharm. 2012 Mar 15;69(6):518-20.

Poon LH, Lee AJ, Chiao TB, Kang GA, Heath S, Glass GA.


Purpose - The expanding role of a clinical pharmacist at a Veterans Affairs (VA) out-patient clinic for patients with Parkinson's disease (PD) and movement disorders is described.
Summary - San Francisco VA Medical Center added a clinical pharmacist to the multi-disciplinary team serving patients at an outpatient clinic operated by its Parkinson's Disease Research, Education and Clinical Center (PADRECC). During the first six months after joining the clinic team, the pharmacist met with 131 patients and made a total of 69 drug therapy recommendations that were implemented by neurologists, clinical nurse specialists, and other PADRECC providers. The results of a retrospective chart review suggested that in about 21% of the cases evaluated, the pharmacist's recommendations contributed to an improved medical outcome or the resolution of a medical problem. Anonymous surveys indicated that clinic providers (n = 33) and patients (n = 20) were satisfied with the pharmacist's services. Using a five-point Likert scale (scores ranged from 1 for "strongly disagree" to 5 for "strongly agree") that they had more time to devote to other clinic responsibilities with the pharmacist present in the clinic (mean score, 4.79); patients indicated that they had an improved understanding of their medications after speaking with the pharmacist (mean score, 4.88).
Conclusion - A clinical pharmacist's regular involvement in an outpatient PD and movement disorders clinic has been well received by patients and clinic providers. The study results suggest that the pharmacist has made important contributions in areas such as therapeutic problem solving and medication education while freeing up providers for other responsibilities.

Wednesday, 7 March 2012

Use of Calcium Channel Blockers and Parkinson's Disease.

Am J Epidemiol. 2012 Mar 1. [Epub ahead of print]
Pasternak B, Svanström H, Nielsen NM, Fugger L, Melbye M, Hviid A.


Experimental evidence and case-control studies suggest that dihydropyridine calcium channel blockers (DiCCBs) may protect against Parkinson's disease. The authors conducted a historical cohort study in Denmark to investigate the association between DiCCB use and risk of Parkinson's disease (1998-2006). Individual-level data on filled drug prescriptions, diagnostic information, and covariates were linked between nationwide registries. Among DiCCB users, 173 incident cases of Parkinson's disease were detected during 461,984 person-years of follow-up, compared with 5,538 cases during 17,343,641 person-years of follow-up among nonusers. After adjustment for age, sex, year, propensity score, and use of other antihypertensive drugs and statins, DiCCB use was associated with a reduced risk of Parkinson's disease (rate ratio (RR) = 0.71, 95% confidence interval (CI): 0.60, 0.82). This association was not present in patients who had previously used DiCCBs (RR = 1.04, 95% CI: 0.87, 1.24). DiCCB users aged ≥65 years were at lower risk of Parkinson's disease than DiCCB users aged <65 years (RR = 0.59, 95% CI: 0.40, 0.85). Among patients with Parkinson's disease, DiCCB use was associated with reduced risk of death (adjusted RR = 0.66, 95% CI: 0.47, 0.91) but not dementia (adjusted RR = 0.97, 95% CI: 0.60, 1.56). In conclusion, DiCCB exposure was associated with a reduced risk of incident Parkinson's disease, particularly in older patients, and with reduced mortality among patients with Parkinson's disease.

Incidence and prevalence of Parkinson's disease in Buenos Aires City, Argentina.

Eur J Neurol. 2012 Mar 5. doi: 10.1111/j.1468-1331.2012.03683.x. [Epub ahead of print]
Bauso DJ, Tartari JP, Stefani CV, Rojas JI, Giunta DH, Cristiano E.


Servicio de Neurología Hospital Italiano de Buenos Aires Investigación en Medicina Interna, Servicio de Clínica Médica Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.


Background and purpose:  Epidemiologic studies of incidence and prevalence in Parkinson's Disease (PD) show highly variable results. Despite the large number of studies performed worldwide during the last decades, little is known about its prevalence in South America and no incidence studies have been performed. The goal of this study is to assess the incidence and prevalence of PD in a health maintenance organization from Buenos Aires City, the capital city of Argentina.

Methods:  The population were all members of the 'Plan de Salud, Hospital Italiano de Buenos Aires', a large prepaid health medical organization in Buenos Aires. From 1 January 2003 to 31 December 2008 patients diagnosed with PD according to Brain Bank of London diagnostic criteria were identified retrospectively. Incidence density was calculated with 95% confidence interval.

Results:  Hundred and forty thousand people were followed for a total of 754,082 person-years. A total of 239 incident cases of PD were identified. Crude incidence density was 31.2/100,000 person-years. Prevalence was 394/100,000 in the population older than 40years. Male to female ratio was 1.31.

Conclusions:  This is the first study in South America that estimates the incidence of PD. Our results are consistent with other studies from other regions using similar methodologies.

Thursday, 1 March 2012

Fatigue in early Parkinson's disease. Minor inconvenience or major distress?

Eur J Neurol. 2012 Feb 16. doi: 10.1111/j.1468-1331.2012.03663.x. [Epub ahead of print]
Herlofson K, Ongre SO, Enger LK, Tysnes OB, Larsen JP.


Department of Neurology, Sorlandet Hospital, Arendal Department of Neurology, Haukeland University Hospital, Bergen Department of Neurology, Stavanger University Hospital and the Norwegian Centre for Movement Disorders, Stavanger University Hospital, Stavanger, Norway.


Background and purpose:  Although fatigue is recognized as a common and debilitating symptom in patients with Parkinson's disease (PD), little is known on how and when this symptom emerges during disease progression. The aim of the study was to explore the presence and severity of fatigue in patients with PD at the time of diagnosis, before dopaminergic treatment has been instituted. Methods:  The present study is part of the Norwegian ParkWest project, a large cohort study of patients with incident PD in Norway. PD was diagnosed according to the Gelb criteria. The study population comprised 199 patients with untreated, newly diagnosed PD and 172 control subjects, matched for gender and age. Fatigue was measured by the Fatigue Severity Scale (FSS). Results:  Fifty-five percent of the patients with PD had clinical significant fatigue (FSS > 4), compared with about 20% of the controls (RR = 2.9). The mean score in patients on the FSS was 4.4 (SD 1.7) and in controls 3.1 (SD 1.3). In addition, there were highly significant differences between patients and controls in each of the nine FSS items. In a regression analysis, only the Montgomery and Åsberg Depression Rating Scale and Unified Parkinson's Disease Rating Scale-Activities of Daily Living scores were significantly associated with fatigue. There was no correlation between fatigue and cognitive impairment and hypersomnia. Conclusion:  Fatigue is a common symptom in PD, also in patients with early, untreated disease, and it has a negative impact on these patients' activity of daily living. Also in early PD, fatigue is an important consideration in the management of patients with the disease.

Adherence to antiparkinsonian medication: An in-depth qualitative study.

Int J Nurs Stud. 2012 Feb 17. [Epub ahead of print]
Drey N, McKeown E, Kelly D, Gould D.



Adherence to prescribed medication is low. It is a major problem as following practitioners' recommendations is strongly associated with good patient outcomes. Little research has been undertaken with people in the early stages of Parkinson's disease although achieving symptom control depends on regularly timing doses.


How do people with Parkinson's disease adhere to prescribed medication, and what are the antecedents of non-adherence to antiparkinsonian medication?


Exploratory qualitative study using semi-structured interviews.


Specialist Parkinson's disease clinic in one National Health Service hospital in England.


Fifteen consecutive patients not yet in the advanced stages of Parkinson's disease living at home and responsible for managing their own medication or managing medication with the help of their carer.


Semi-structured interviews with open questions.


Each respondent demonstrated at least one type and in most cases several different types of non-adherent behaviour. Inadvertent minor non-adherence occurred because patients forgot to take tablets or muddled doses. Minor deliberate deviations occurred when patients took occasional extra tablets or brought forward doses to achieve better symptom control, often to cater for situations that were anticipated as especially demanding. Deliberate major non-adherence was very common and always related to over-use of medication. The experiences of parkinsonism were particular to the individual. The specific circumstances that prompted an episode of non-adherence varied between patients. Nevertheless there was evidence of negotiation between respondents and the Parkinson's disease nurse specialist; medication regimes were altered in conjunction with the patient during formal consultations and by telephone.


Non-adherence to prescribed medication for people with chronic conditions is complex and for people with Parkinson's disease it was possible to identify different types of non-adherence. The possible existence of a typology of non-adherence for people with other chronic conditions merits investigation. Further research is needed to establish whether the findings of this small scale qualitative study can be replicated with a larger, more representative sample and establish how people with Parkinson's disease might be encouraged to adhere to medication regimes to improve symptom control.

Parkinson's disease, insulin resistance and novel agents of neuroprotection.

Brain. 2012 Feb 17. [Epub ahead of print]

Aviles-Olmos I, Limousin P, Lees A, Foltynie T.


Multiple avenues of research including epidemiology, molecular genetics and cell biology have identified links between Parkinson's disease and type 2 diabetes mellitus. Several recent discoveries have highlighted common cellular pathways that potentially relate neurodegenerative processes with abnormal mitochondrial function and abnormal glucose metabolism. This includes converging evidence identifying that peroxisome proliferator activated receptor gamma coactivator 1-α, a key regulator of enzymes involved in mitochondrial respiration and insulin resistance, is potentially pivotal in the pathogenesis of neurodegeneration in Parkinson's disease. This evidence supports further study of these pathways, most importantly to identify neuroprotective agents for Parkinson's disease, and/or establish more effective prevention or treatment for type 2 diabetes mellitus. In parallel with these advances, there are already randomized trials evaluating several established treatments for insulin resistance (pioglitazone and exenatide) as possible disease modifying drugs in Parkinson's disease, with only preliminary insights regarding their mechanisms of action in neurodegeneration, which may be effective in both disease processes through an action on mitochondrial function. Furthermore, parallels are also emerging between these same pathways and neurodegeneration associated with Alzheimer's disease and Huntington's disease. Our aim is to highlight this converging evidence and stimulate further hypothesis-testing studies specifically with reference to the potential development of novel neuroprotective agents in Parkinson's disease.

Hyposmia and cognitive impairment in Gaucher disease patients and carriers.

Mov Disord. 2012 Feb 16. doi: 10.1002/mds.24945. [Epub ahead of print]

McNeill A, Duran R, Proukakis C, Bras J, Hughes D, Mehta A, Hardy J, Wood NW, Schapira AH.


Department of Clinical Neuroscience, University College London (UCL) Institute of Neurology, Royal Free Hospital, London, United Kingdom.


The objective of this study was to assess a cohort of Gaucher disease patients and their heterozygous carrier relatives for potential clinical signs of early neurodegeneration. Gaucher disease patients (n = 30), heterozygous glucocerebrosidase mutation carriers (n = 30), and mutation-negative controls matched by age, sex, and ethnicity (n = 30) were recruited. Assessment was done for olfactory function (University of Pennsylvania Smell Identification Test), cognitive function (Mini-Mental State Examination, Montreal Cognitive Assessment), rapid eye movement sleep disorder, autonomic symptoms, and parkinsonian motor signs (Unified Parkinson's Disease Rating Scale part III, Purdue pegboard). Olfactory function scores were significantly lower in Gaucher disease patients (P = .010) and heterozygous carriers (P < .001) than in controls. Cognitive assessment scores were significantly lower in Gaucher disease patients (P = .002) and carriers (P = .002) than in controls. Unified Parkinson's Disease Rating Scale motor subscale scores were significantly higher in Gaucher disease patients (P < .001) and heterozygotes (P = .0010) than in controls. There was no difference in scores for symptoms of rapid eye movement sleep disorder or autonomic dysfunction. Impairment of olfaction, cognition, and parkinsonian motor signs occurs more frequently in Gaucher disease patients and carriers than in controls, which may indicate the early stages of neurodegeneration. © 2012 Movement Disorder Society.

Mild cognitive impairment in Parkinson disease: heterogenous mechanisms.

J Neural Transm. 2012 Feb 18. [Epub ahead of print]

Jellinger KA.


Cognitive impairment is common in Parkinson disease (PD), with long-term longitudinal studies reporting that most PD patients develop dementia. A high proportion of patients with PD and mild cognitive impairment (MCI) progress to dementia within a short time. Impairments occur in a range of cognitive domains, but single-domain impairment is more common than multiple one, non-amnestic more common than amnestic impairment. Although the term MCI applied to PD (PD-MCI) is not without controversy due to the lack of uniform diagnostic consensus criteria, the biological validity of PD-MCI is supported by many recent studies that show heterogenous mechanisms in the clinical presentation, neuropsychology, neuroimaging, biomarkers, and neuropathology, suggesting abnormal metabolic network activities involving several cortical and subcortical nervous systems. Prospective studies using specific biomarkers, including amyloid imaging, and cerebro-spinal fluid biomarkers are warranted for an exact diagnosis and prognostic assessment of early cognitive deficits in PD patients.

Plain English - LRRK2 G2019S Parkinson's disease with more benign phenotype than idiopathic

This research study compared patients with Parkinson's who carry the commonest gene mutation associated with the disease (called LRRK2),...