The heterogeneity of early Parkinson's disease: a cluster analysis on newly diagnosed untreated patients

PLoS One. 2013 Aug 1;8(8):e70244. doi: 10.1371/journal.pone.0070244. Print 2013.

Erro R, Vitale C, Amboni M, Picillo M, Moccia M, Longo K, Santangelo G, De Rosa A, Allocca R, Giordano F, Orefice G, De Michele G, Santoro L, Pellecchia MT, Barone P.

Source

Sobell Department of Motor Neuroscience and Movement Disorders, University College London (UCL), London, United Kingdom.

Abstract

BACKGROUND:

The variability in the clinical phenotype of Parkinson's disease seems to suggest the existence of several subtypes of the disease. To test this hypothesis we performed a cluster analysis using data assessing both motor and non-motor symptoms in a large cohort of newly diagnosed untreated PD patients.

METHODS:

We collected data on demographic, motor, and the whole complex of non-motor symptoms from 100 consecutive newly diagnosed untreated outpatients. Statistical cluster analysis allowed the identification of different subgroups, which have been subsequently explored.

RESULTS:

THE DATA DRIVEN APPROACH IDENTIFIED FOUR DISTINCT GROUPS OF PATIENTS, WE HAVE LABELED: 1) Benign Pure Motor; 2) Benign mixed Motor-Non-Motor; 3) Non-Motor Dominant; and 4) Motor Dominant.

CONCLUSION:

Our results confirmed the existence of different subgroups of early PD patients. Cluster analysis revealed the presence of distinct subtypes of patients profiled according to the relevance of both motor and non-motor symptoms. Identification of such subtypes may have important implications for generating pathogenetic hypotheses and therapeutic strategies.

Prevalence and clinical course of olfactory hallucinations in idiopathic Parkinson's disease

J Parkinsons Dis. 2012;2(3):199-205. doi: 10.3233/JPD-2012-012086.

McAuley JH, Gregory S.

Source

Department of Neurology, King George Hospital, Barking Havering & Redbridge University Hospitals Trust, Romford, Essex, UK Department of Neurosciences, Royal London Hospital, Whitechapel, UK.

Abstract

Background: Olfactory hallucinations are known to occur in idiopathic Parkinson's disease (IPD) but are much less well-described than visual hallucinations. Objective: To report the prevalence, clinical features, response to treatment and prognosis of olfactory hallucinations in IPD. Methods: 205 consecutively reviewed IPD patients and 205 non-IPD control patients attending the local hospital were surveyed for the presence of olfactory hallucinations by specific questioning; the IPD patients were followed up for at least three years. Results: Of 188 patients who had a clinical course remaining consistent with IPD, four were initially found to have olfactory hallucinations, yielding a prevalence of 2.1% (95% confidence interval 0.4-5.4%). Two further patients developed such hallucinations later during the study. Olfactory hallucinations were not always accompanied by other hallucination modalities. The patients had a long duration of disease treated with dopaminergic medication, loss of sense of smell typical for IPD, no dementia or features suggestive of non-idiopathic PD after three years follow-up, a lack of insight into their hallucinations with consequent failure to report them spontaneously, and a good and lasting response to modest doses of atypical antipsychotics. Conclusions: This study confirms the significant prevalence of olfactory hallucinations, describes their clinical features and indicates that they may occur in isolation and not predict other psychotic or dementing features. The nuisance that such hallucinations cause, their ease of treatment and their failure to be volunteered as a symptom means that specific questioning for their presence should be included in routine assessment of patients with IPD.

Colonic Neuropathology is Independent of Olfactory Dysfunction in Parkinson's Disease

J Parkinsons Dis. 2011;1(4):389-94. doi: 10.3233/JPD-2011-11061.

Lebouvier T, Pouclet H, Coron E, Drouard A, N'guyen JM, Roy M, Vavasseur F, Bruley des Varannes S, Damier P, Neunlist M, Derkinderen P, Rouaud T.

Source

Inserm, U913, Nantes, France Inserm, CIC-04, Nantes, France University Nantes, Nantes, France CHU Nantes, Department of Neurology, Nantes, France CHU Nantes, Institut des Maladies de l'Appareil Digestif, Nantes, France.

Abstract

Olfactory dysfunction (OD) and constipation are two frequent and early non-motor features of Parkinson's disease (PD). Colonic PD neuropathology, the putative cause of constipation, can be analyzed and quantified using routine colonic biopsies and parallels disease severity. The present study was aimed at investigating whether the severity of neuropathology in the colon in PD is related to OD. Twenty-six PD patients were included. Colonic neuropathology, i.e., the density of Lewy pathology and the number of submucosal neurons, was unrelated to OD as assessed using the University of Pennsylvania Smell Identification. This suggests that unlike colonic Lewy pathology, OD is unrelated to disease severity.

Cognitive behavioral therapy for depression and anxiety in Parkinson's disease: a clinical review

J Parkinsons Dis. 2012;2(2):135-51. doi: 10.3233/JPD-2012-12080.

Armento ME, Stanley MA, Marsh L, Kunik ME, York MK, Bush AL, Calleo JS.

Source

Houston VA Health Services Research and Development Center of Excellence, Michael E. DeBakey VA Medical Center, Houston, TX, USA Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, USA VA South Central Mental Illness, Research, Education, and Clinical Center (MIRECC), Houston, TX, USA.

Abstract

Parkinson's disease (PD) is the second most common neurodegenerative disorder. It is generally defined by its progressive motor features; but increased attention is being paid to its non-motor neuropsychiatric symptoms, which profoundly impact quality of life for patients and caregivers. Anxiety and depression are particularly problematic and are the strongest predictors of quality of life in PD. Recent research has focused on non-pharmacological approaches to treating depression and anxiety in patients with PD. Cognitive-behavioral therapy (CBT) is a potentially efficacious non-pharmacological treatment for mood and anxiety symptoms associated with PD. Accordingly, this review examines empirical studies of CBT-based treatments for depression and anxiety symptoms in PD. Medical Subject Headings were used in searches of PsychInfo and PubMed of English-language articles published in peer-reviewed journals, resulting in the identification of 10 articles. Four additional articles were identified from the references of these articles and upon the suggestions of experts, for 15 articles in all. Results of individual studies varied significantly; however, the randomized controlled trials showed encouraging results and support the need for further investigation of the utility of CBT for depressed and anxious patients with PD. CBT is potentially a useful treatment for patients with PD and comorbid depression and/or anxiety, but more systematic research will be necessary to measure its effects.

Declining quality of life in Parkinson disease before and after diagnosis

J Parkinsons Dis. 2012;2(2):153-60. doi: 10.3233/JPD-2012-12083.

Palacios N, Gao X, Schwarzschild M, Ascherio A.

Source

Department of Nutrition, Harvard School of Public Health, Boston, MA, USA.

Abstract

We sought to assess the quality of life in PD patients before the diagnosis, in comparison to age-matched individuals free of PD, among participants in two large prospective cohorts of men and women. Components of the Short-Form Health Status Survey (SF36) were administered to all participants in 1996 and 2008 in the Health Professionals Follow-up Study (HPFS), and in 1992, 1996, 2000 and 2004 in the Nurses' Health Study (NHS). We used scores in 7 health-related quality of life-dimensions, that were rated from 1(worst) to 100(best) points. We fitted a multivariate mixed-effect model with repeated measures to estimate the expected decline with age and compared that to the decline observed among PD cases by time to diagnosis. 454 men and 414 women with PD contributed data to the analyses. A decline in physical function in PD patients relative to the whole cohort began approximately 7.5 years prior to diagnosis in women and 3 years prior to diagnosis in men, and continued to decline thereafter with a rate of 2.35 and 1.43 points per year in women and men respectively (p < 0.001 for both). For comparison, the average yearly decline in individuals without PD was 0.42 and 0.23 points per year in women and men respectively. Other measures of quality of life (only available in women) declined in a similar pattern to physical function. In summary, the quality of life in PD patients begins to decline years before the diagnosis.

Sleep benefit in Parkinson's disease: time to revive an enigma?

J Parkinsons Dis. 2012;2(2):167-70. doi: 10.3233/JPD-2012-12087.

van Gilst MM, Louter M, Baumann CR, Bloem BR, Overeem S.

Source

Department of Neurology, Donders Institute for Brain, Cognition and Behavior, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.

Abstract

Some patients with Parkinson's disease (PD) reportedly experience 'sleep benefit': an improved motor functioning upon awaking in the morning. In this questionnaire study, 114 out of 243 consecutive outpatients with PD (46.9%) subjectively experienced sleep benefit. Among those patients that regularly took an afternoon nap, 33.7% experienced sleep benefit after the nap as well. Between patients with and without sleep benefit, there were no differences in demographic or clinical variables, including age, disease duration, dopaminergic treatment, and nocturnal sleep quality. Sleep benefit remains an intriguing but elusive phenomenon, which deserves renewed attention and further research.

REM sleep behavior disorder and motor dysfunction in Parkinson's disease - A longitudinal study

Parkinsonism Relat Disord. 2013 Aug 5. pii: S1353-8020(13)00271-X. doi: 10.1016/j.parkreldis.2013.07.017. [Epub ahead of print]

Bugalho P, Viana-Baptista M.

Source

Neurology Department Hospital de Egas Moniz (CHLO), Lisboa, Portugal; Departamento de Neurologia, CEDOC, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, 1169-056 Lisbon, Portugal. 

Abstract

OBJECTIVES:

Longitudinal assessment of a Parkinson's disease (PD) cohort, to investigate the evolution or REM sleep behavior symptoms (RBD) over time and to test the relation between RBD at onset and motor dysfunction progression.

METHODS:

An early stage PD cohort (n = 61) was assessed at two time points, separated by a two years interval. Diagnostic criteria for RBD were: violent behavior during sleep and body movements or vocalization indicative of dream enacting and at least six affirmative answers in the REM sleep behavior disorder screening questionnaire. Motor function assessment was performed with the Unified Parkinson's Disease Scale part II and III (total and partial scores for tremor, bradykinesia, rigidity, gait/postural instability and dysarthria).

RESULTS:

25 Patients had RBD at baseline, vs. 35 at follow-up. Three RBD changed to non-RBD at follow-up, while 10 non-RBD patients developed RBD at follow-up (annual incidence of 12.5%). RBD and non-RBD patients did not differ significantly at baseline or follow-up. The presence of RBD at baseline was significantly related to an increase in UPDRS total and bradykinesia scores over time.

DISCUSSION:

RBD symptoms can vary over time and have a tendency to increase during the early stages of disease. The presence of RBD symptoms could be a risk factor for motor function deterioration and particularly for bradykinesia worsening.

Dementia with Lewy bodies: early diagnostic challenges

Psychogeriatrics. 2013 Jun;13(2):128-38. doi: 10.1111/psyg.12005.

Fujishiro H, Iseki E, Nakamura S, Kasanuki K, Chiba Y, Ota K, Murayama N, Sato K.

Source

PET/CT Dementia Research Center, Juntendo Tokyo Koto Geriatric Medical Center; Department of Psychiatry, Juntendo University School of Medicine, Tokyo, Japan.

Abstract

Dementia with Lewy bodies (DLB) is defined pathologically as neurodegeneration associated with Lewy bodies (LB). LB-related symptoms, including olfactory dysfunction, dysautonomia, and mood and sleep disorders, are increasingly recognized as clinical signs that enable the early detection of DLB, because these symptoms often antedate dementia by years or even decades. It remains unknown if the clinical history of LB-related symptoms is sufficient for the prodromal state of DLB to be suspected in memory clinics. We retrospectively investigated the clinical courses, including olfactory dysfunction, dysautonomia, depression, and rapid eye movement sleep behaviour disorder, of 90 patients with probable DLB. The timing of LB-related symptoms that preceded or followed relative to the onset of memory loss was calculated. LB-related symptoms were present in 79 of 90 patients (87.8%) with probable DLB before or at the time of memory loss onset. These symptoms preceded the onset of memory loss between 1.2 and 9.3 years. We also report on four non-demented patients with a clinical history of LB-related symptoms in our memory clinic. All four patients showed reduced cardiac [(123) I]-metaiodobenzylguanidine levels. Moreover, [(18) F]fluoro-D-glucose positron emission tomography scans revealed glucose hypometabolism in the occipital cortex in two patients. One patient converted to probable DLB with the development of parkinsonism 2 years after major depression was diagnosed. Based on a clinical history of LB-related symptoms, we propose a conceptual framework to identify these symptomatic but non-demented individuals that led us to suspect the underlying pathophysiology of Lewy body disease. Further prospective study is warranted to determine the clinical significance of LB-related symptoms in non-demented patients.

Population-specific frequencies for LRRK2 susceptibility variants in the genetic epidemiology of Parkinson's disease (GEO-PD) consortium

Mov Disord. 2013 Aug 2. doi: 10.1002/mds.25600. [Epub ahead of print]

Heckman MG, Soto-Ortolaza AI, Aasly JO, Abahuni N, Annesi G, Bacon JA, Bardien S, Bozi M, Brice A, Brighina L, Carr J, Chartier-Harlin MC, Dardiotis E, Dickson DW, Diehl NN, Elbaz A, Ferrarese C, Fiske B, Gibson JM, Gibson R, Hadjigeorgiou GM, Hattori N, Ioannidis JP, Boczarska-Jedynak M, Jasinska-Myga B, Jeon BS, Kim YJ, Klein C, Kruger R, Kyratzi E, Lesage S, Lin CH, Lynch T, Maraganore DM, Mellick GD, Mutez E, Nilsson C, Opala G, Park SS, Petrucci S, Puschmann A, Quattrone A, Sharma M, Silburn PA, Sohn YH, Stefanis L, Tadic V, Theuns J, Tomiyama H, Uitti RJ, Valente EM, Van Broeckhoven C, van de Loo S, Vassilatis DK, Vilariño-Güell C, White LR, Wirdefeldt K, Wszolek ZK, Wu RM, Hentati F, Farrer MJ, Ross OA; on behalf of the Genetic Epidemiology of Parkinson's Disease (GEO-PD) Consortium.

Source

Biostatistics Unit, Mayo Clinic, Jacksonville, Florida, USA.

Abstract

BACKGROUND:

Variants within the leucine-rich repeat kinase 2 gene are recognized as the most frequent genetic cause of Parkinson's disease. Leucine-rich repeat kinase 2 variation related to disease susceptibility displays many features that reflect the nature of complex, late-onset sporadic disorders like Parkinson's disease.

METHODS:

The Genetic Epidemiology of Parkinson's Disease Consortium recently performed the largest genetic association study for variants in the leucine-rich repeat kinase 2 gene across 23 different sites in 15 countries.

RESULTS:

Herein, we detail the allele frequencies for the novel risk factors (p.A419V and p.M1646T) and the protective haplotype (p.N551K-R1398H-K1423K) nominated in the original publication. Simple population allele frequencies not only can provide insight into the clinical relevance of specific variants but also can help genetically define patient groups.

CONCLUSIONS:

Establishing individual patient-based genomic susceptibility profiles that incorporate both risk factors and protective factors will determine future diagnostic and treatment strategies.

Impulse control disorders in Parkinson's disease: decreased striatal dopamine transporter levels

J Neurol Neurosurg Psychiatry. 2013 Jul 30. doi: 10.1136/jnnp-2013-305395. [Epub ahead of print]

Voon V, Rizos A, Chakravartty R, Mulholland N, Robinson S, Howell NA, Harrison N, Vivian G, Ray Chaudhuri K.

Source

Department of Psychiatry, University of Cambridge, , Cambridge, UK.

Abstract

OBJECTIVE:

Impulse control disorders are commonly associated with dopaminergic therapy in Parkinson's disease (PD). PD patients with impulse control disorders demonstrate enhanced dopamine release to conditioned cues and a gambling task on [11C]raclopride positron emission tomography (PET) imaging and enhanced ventral striatal activity to reward on functional MRI. We compared PD patients with impulse control disorders and age-matched and gender-matched controls without impulse control disorders using [123I]FP-CIT (2β-carbomethoxy-3β-(4-iodophenyl)tropane) single photon emission computed tomography (SPECT), to assess striatal dopamine transporter (DAT) density.

METHODS:

The [123I]FP-CIT binding data in the striatum were compared between 15 PD patients with and 15 without impulse control disorders using independent t tests.

RESULTS:

Those with impulse control disorders showed significantly lower DAT binding in the right striatum with a trend in the left (right: F(1,24)=5.93, p=0.02; left: F(1,24)=3.75, p=0.07) compared to controls.

CONCLUSIONS:

Our findings suggest that greater dopaminergic striatal activity in PD patients with impulse control disorders may be partly related to decreased uptake and clearance of dopamine from the synaptic cleft. Whether these findings are related to state or trait effects is not known. These findings dovetail with reports of lower DAT levels secondary to the effects of methamphetamine and alcohol. Although any regulation of DAT by antiparkinsonian medication appears to be modest, PD patients with impulse control disorders may be differentially sensitive to regulatory mechanisms of DAT expression by dopaminergic medications.

Poor self-awareness of levodopa-induced dyskinesias in Parkinson's disease: Clinical features and mechanisms

Parkinsonism Relat Disord. 2013 Jul 23. pii: S1353-8020(13)00241-1. doi: 10.1016/j.parkreldis.2013.07.002. [Epub ahead of print]

Pietracupa S, Fasano A, Fabbrini G, Sarchioto M, Bloise M, Latorre A, Altieri M, Bologna M, Berardelli A.

Source

Department of Neurology and Psychiatry, Sapienza University of Rome, Italy.

Abstract

OBJECTIVES:

To study the factors and possible mechanisms associated with decreased self-awareness of levodopa-induced dyskinesias (LIDs) in patients with Parkinson's disease (PD).

METHODS:

We enrolled 30 PD patients with LIDs. Patients were video-recorded in an "on" phase while experiencing LIDs. LIDs were objectively rated by means of the Unified Dyskinesias Rating Scale (UDyRS) by two movement disorders specialists while examining the patients. Patients were asked to rate the body site and the severity of their LIDs according to the 5-point UDyRS. Patients then rated their own LIDs while watching the video recording of themselves. Lastly, the patients rated the LIDs of other reference PD patients on a video recording. The same reference video recordings were shown to 15 healthy individuals matched for age, gender and education.

RESULTS:

Seven of the 30 PD patients investigated were subjectively unaware of the presence of their LIDs. The majority of patients, however, recognized their LIDs when watching video recording of themselves. Patients displayed a specific poor self-awareness of trunk LIDs, in both the subjective evaluation and in the video recording-based subjective evaluation. By contrast PD patients correctly recognized LIDs in video recordings of reference PD patients. Poor self-awareness correlated with predominance of motor symptoms on the left body side.

CONCLUSIONS:

Poor self-awareness of LIDs is present in a proportion of PD patients as a form of anosognosia. The poor self-awareness of LIDs in the trunk is likely to be due to a complex interplay involving both anosognosic mechanisms and deficits in proprioceptive axial kinesthesia.