Association of Cerebrospinal Fluid β-Amyloid 1-42, T-tau, P-tau181, and α-Synuclein Levels With Clinical Features of Drug-Naive Patients With Early Parkinson Disease

JAMA Neurol. 2013 Aug 26. doi: 10.1001/jamaneurol.2013.3861. [Epub ahead of print]

Kang JH, Irwin DJ, Chen-Plotkin AS, Siderowf A, Caspell C, Coffey CS, Waligórska T, Taylor P, Pan S, Frasier M, Marek K, Kieburtz K, Jennings D, Simuni T, Tanner CM, Singleton A, Toga AW, Chowdhury S, Mollenhauer B, Trojanowski JQ, Shaw LM; and the Parkinson’s Progression Markers Initiative.

Source

Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia2Department of Pharmacology, Inha University School of Medicine, Incheon, Republic of Korea.

Abstract

IMPORTANCE We observed a significant correlation between cerebrospinal fluid (CSF) levels of tau proteins and α-synuclein, but not β-amyloid 1-42 (Aβ1-42), and lower concentration of CSF biomarkers, as compared with healthy controls, in a cohort of entirely untreated patients with Parkinson disease (PD) at the earliest stage of the disease studied so far. OBJECTIVE To evaluate the baseline characteristics and relationship to clinical features of CSF biomarkers (Aβ1-42, total tau [T-tau], tau phosphorylated at threonine 181 [P-tau181], and α-synuclein) in drug-naive patients with early PD and demographically matched healthy controls enrolled in the Parkinson's Progression Markers Initiative (PPMI) study. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional study of the initial 102 research volunteers (63 patients with PD and 39 healthy controls) of the PPMI cohort. MAIN OUTCOMES AND MEASURES The CSF biomarkers were measured by INNO-BIA AlzBio3 immunoassay (Aβ1-42, T-tau, and P-tau181; Innogenetics Inc) or by enzyme-linked immunosorbent assay (α-synuclein). Clinical features including diagnosis, demographic characteristics, motor, neuropsychiatric, and cognitive assessments, and DaTscan were systematically assessed according to the PPMI study protocol. RESULTS Slightly, but significantly, lower levels of Aβ1-42, T-tau, P-tau181, α-synuclein, and T-tau/Aβ1-42 were seen in subjects with PD compared with healthy controls but with a marked overlap between groups. Using multivariate regression analysis, we found that lower Aβ1-42 and P-tau181 levels were associated with PD diagnosis and that decreased CSF T-tau and α-synuclein were associated with increased motor severity. Notably, when we classified patients with PD by their motor phenotypes, lower CSF Aβ1-42 and P-tau181 concentrations were associated with the postural instability-gait disturbance-dominant phenotype but not with the tremor-dominant or intermediate phenotype. Finally, we found a significant correlation of the levels of α-synuclein with the levels of T-tau and P-tau181. CONCLUSIONS AND RELEVANCE In this first report of CSF biomarkers in PPMI study subjects, we found that measures of CSF Aβ1-42, T-tau, P-tau181, and α-synuclein have prognostic and diagnostic potential in early-stage PD. Further investigations using the entire PPMI cohort will test the predictive performance of CSF biomarkers for PD progression.

Inpatient management of Parkinson disease: current challenges and future directions

Neurohospitalist. 2012 Jan;2(1):28-35. doi: 10.1177/1941874411427734.

Oguh O, Videnovic A.

Source

Northwestern University, Chicago, IL, USA.

Abstract

Parkinson disease (PD) is usually managed through outpatient clinical care. Reasons for hospital admissions are either directly related to PD or may reflect comorbidities. When hospitalized, patients with PD may face many challenges. Most commonly these are related to medication management, falls, mental status changes, infections, and emergence of psychiatric symptoms. Timely recognition and proper management of PD-specific hospitalization-related problems may be delayed, given the common lack of expertise in PD management of hospital physicians, nurses, and allied health professionals. With increasing prevalence of PD, it is expected that more patients will require inpatient hospital care. It is therefore very important to recognize problems that may arise upon hospitalization of a patient with PD and provide education to health care professionals involved in the inpatient care of patients with PD. This approach may lead to reductions in complication rates and duration of hospital stays.

AIM:

In this review, we outline the most common reasons for hospitalization of patients with PD, discuss challenges related to inpatient hospital care of patients with PD, and comment on future directions aimed at optimizing hospitalization outcomes in the population with PD.

"Getting this right is vitally important for people with PD. Inappropriate admissions and mis-management can result in lengthy hospital stays for people with PD" - Alastair Noyce

The Contribution of Apathy and Increased Learning Trials to Risky Decision-Making in Parkinson's Disease

Arch Clin Neuropsychol. 2013 Aug 21. [Epub ahead of print]

Buelow MT, Frakey LL, Grace J, Friedman JH.

Source

Department of Psychology, The Ohio State University Newark, Newark, OH, USA.

Abstract

Impairments in executive functioning are commonly found in Parkinson's disease (PD); however, the research into risky decision making has been mixed. The present study sought to investigate three potential hypotheses: difficulty learning the task probabilities, levodopa equivalent dose (LED), and the presence of apathy. Twenty-four individuals with idiopathic PD and 13 healthy controls completed the Frontal Systems Behavior Scale to assess current apathy, the Iowa Gambling Task, and the Balloon Analog Risk Task (BART). Results indicated that individuals with PD selected more from Deck B, a disadvantageous deck. However, with an additional set of trials, participants with PD and apathy selected more from the most risky deck (Deck A). Apathy was not related to the BART, and LED was not related to either task. Results indicate that apathy is associated with decision-making in PD, and providing additional learning trials can improve decision-making in PD without apathy.

Nintendo Wii rehabilitation ("Wii-hab") provides benefits in Parkinson's disease

Parkinsonism Relat Disord. 2013 Aug 19. pii: S1353-8020(13)00268-X. doi: 10.1016/j.parkreldis.2013.07.014. [Epub ahead of print]

Herz NB, Mehta SH, Sethi KD, Jackson P, Hall P, Morgan JC.

Source

Movement Disorders Program, Department of Neurology, Georgia Regents University, 1429 Harper Street, HF-1154, Augusta, GA 30912, USA.

Abstract

Parkinson's disease (PD) impairs both activities of daily living (ADLs) and motor function and has adverse effects on mood in many patients. While dopaminergic medications are quite helpful for motor and ADLs impairments in PD, complementary therapies are also important in helping patients achieve maximum benefits and quality of life. We hypothesized that the Nintendo Wii (Wii) is a useful tool in improving motor and non-motor aspects in patients with PD, given its ability to drive functional movements and interactive nature. We enrolled twenty subjects with early to mid-stage PD in an open-label within-subjects study design where each subject was evaluated at baseline and then re-evaluated after playing the Wii three times per week for four weeks. Subjects were then re-evaluated one month later after not playing the Wii for a month to see if effects carried over. Subjects demonstrated significant improvements in the primary outcome measure (Nottingham Extended Activities of Daily Living Test (NEADL)), quality of life (PDQ-39) and motor function (UPDRS), and a trend toward improved mood (HAM-D) after four weeks of Wii therapy. Follow-up assessments one month later showed continued improvement for quality of life and UPDRS scores. The results demonstrate that Wii therapy provides short-term motor, non-motor, and quality of life benefits in PD. Further studies are needed to determine if there are long-term benefits of Wii therapy in PD.

Baseline [123 I]FP-CIT SPECT (DaTSCAN) severity correlates with medication use at 3 years in Parkinson's disease

Acta Neurol Scand. 2013 Aug 20. doi: 10.1111/ane.12178. [Epub ahead of print]

Nissen T, Malek N, Grosset KA, Newman EJ, Patterson J, Hadley D, Grosset DG.

Source

Department of Neurology, Klinikum Bremerhaven, Bremerhaven, Germany.

Abstract

BACKGROUND:

Presynaptic dopaminergic deficiency on dopamine transporter imaging supports a clinical diagnosis of Parkinson's disease and correlates with the severity of rigidity and bradykinesia. Baseline dopaminergic deficiency predicts clinical severity, but the relationship with subsequent medication use has not been reported.

METHODS:

A randomly selected cross section of 83 Parkinson's disease (PD) patients who had [123 I] FP-CIT SPECT at the time of clinical diagnosis was identified. Dopaminergic deficiency was graded 1, 2 or 3 with increasing severity using visual assessment and by semiquantitative analysis of putamen and caudate uptake. Antiparkinson medication usage and clinical severity by Hoehn and Yahr were noted annually to 3 years.

RESULTS:

In 83 patients (66% male, median age 65.0 years, IQ 55.4-71.8), [123 I]FP-CIT SPECT was grade 1 in 20 (24%), grade 2 in 53 (64%) and grade 3 in 10 patients (12%). Dopamine transporter uptake ratios were inversely associated with antiparkinson medication usage (r = -0.26, P = 0.0201) and Hoehn Yahr stage (r = -0.32, P = 0.0029) at 3 years from baseline, but there was considerable variation in drug usage in individual patients. At 3 years, patients with grade 1 scans at baseline received a median dose of 325 levodopa equivalent units (LEU) (interquartile range 175-433); grade 2 scan patients 400 LEU (interquartile range 300-635); and grade 3 scan patients 460 LEU (interquartile range 252-658).

CONCLUSION:

The degree of reduction in presynaptic dopaminergic uptake at baseline is associated with higher antiparkinson drug dosage at follow-up, but the wide variation means that the baseline FP-CIT SPECT does not reliably predict drug use in individual cases.

Repeat expansion in C9ORF72 is not a major cause of amyotrophic lateral sclerosis among Iranian patients

Neurobiol Aging. 2013 Aug 17. pii: S0197-4580(13)00321-7. doi: 10.1016/j.neurobiolaging.2013.07.016. [Epub ahead of print]

Alavi A, Nafissi S, Rohani M, Shahidi G, Zamani B, Shamshiri H, Safari I, Elahi E.

Source

School of Biology, College of Science, University of Tehran, Tehran, Iran.

Abstract

Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease in populations of European descent. It was recently found that a hexanucleotide repeat expansion in C9ORF72 is its most common cause in these populations. The contribution of C9ORF72 to ALS is notably lower in the Far East, but its role in other populations is unknown. Results of C9ORF72 screening in 78 unrelated Iranian ALS patients are reported here. The repeat expansion was observed in only 1 (5.9%) of the familial and 1 (1.6%) of the sporadic cases. These figures are to be compared, respectively, with 30% and 6.9% among patients of European ethnicity. Screenings of C9ORF72 in other Middle East countries will reveal whether the low contribution of C9ORF72 to ALS is a feature of the entire region. During the screenings, it was noted that in a single family, 3 individuals affected with ALS, Parkinson's disease, or frontotemporal dementia all carried the repeat expansion. The finding suggests the mutation does rarely contribute to the etiology of Parkinson's disease.

The timing between REM sleep behavior disorder and Parkinson's disease

Sleep Breath. 2013 Aug 21. [Epub ahead of print]

Ferri R, Cosentino FI, Pizza F, Aricò D, Plazzi G.

Source

Sleep Research Centre, Department of Neurology I.C., Oasi Institute for Research on Mental Retardation and Brain Aging (IRCCS), Via C. Ruggero 73, 94018, Troina, Italy

Abstract

PURPOSE:

In Parkinson's disease (PD) patients, REM sleep behavior disorder (RBD) might precede PD or develop with or after the onset of PD. No previous study has explored differences between these two groups. The aim of this study was therefore to compare clinical features and REM sleep chin electromyographic patterns between patients in whom RBD heralded PD and those in whom RBD occurrence coincided with or followed the clinical manifestations of PD.

METHOD:

Twenty-seven consecutive PD patients (mean age 67.9 years) were enrolled. Detailed clinical, laboratory, and polysomnographic studies were obtained in all participants.

RESULTS:

Sixteen of the 27 patients were affected by RBD. These had a significantly higher stage of PD and took significantly higher doses of dopaminergic therapy; their disease duration tended to be longer, and their cognitive status tended to be lower. PD patients in whom RBD preceded PD (n = 6) did not differ from PD patients without RBD in disease parameters, while PD patients in whom RBD developed with or after PD (n = 10) showed a significantly higher disease stage, took significantly higher dopaminergic therapy, and had a longer disease duration.

CONCLUSION:

Our findings are compatible with the hypothesis that patients in whom RBD precedes, or does not precede, PD might constitute two possibly distinct clinical and physiopathological groups, based on different progressive neuropathological sequences of events.

PREDICT-PD baseline results publication now Open Access

http://jnnp.bmj.com/content/early/2013/08/18/jnnp-2013-305420.long

J Neurol Neurosurg Psychiatry. 2013 Aug 18. doi: 10.1136/jnnp-2013-305420. [Epub ahead of print]

PREDICT-PD: Identifying risk of Parkinson's disease in the community: methods and baseline results.

Noyce AJ, Bestwick JP, Silveira-Moriyama L, Hawkes CH, Knowles CH, Hardy J, Giovannoni G, Nageshwaran S, Osborne C, Lees AJ, Schrag A.

Source

Reta Lila Weston Institute of Neurological Studies, UCL Institute of Neurology, London, UK.

Abstract

OBJECTIVES:

To present methods and baseline results for an online screening tool to identify increased risk for Parkinson's disease (PD) in the UK population.

METHODS:

Risk estimates for future PD were derived from the results of a systematic review of risk factors and early features of PD. Participants aged 60-80 years without PD were recruited by self-referral. They completed an online survey (including family history, non-motor symptoms and lifestyle factors), a keyboard-tapping task and the University of Pennsylvania Smell Identification Test. Risk scores were calculated based on survey answers. Preliminary support for the validity of this algorithm was assessed by comparing those estimated to be higher risk for PD with those at lower risk using proxies, including smell loss, REM-sleep behaviour disorder and reduced tapping speed, and by assessing associations in the whole group.

RESULTS:

1324 eligible participants completed the survey and 1146 undertook the keyboard-tapping task. Smell tests were sent to 1065 participants. Comparing the 100 highest-risk participants and 100 lowest-risk participants, median University of Pennsylvania Smell Identification Test scores were 30/40 versus 33/40 (p<0.001), mean number of key taps in 30 s were 55 versus 58 (p=0.045), and 24% versus 10% scored above cut-off for REM-sleep behaviour disorder (p=0.008). Regression analyses showed increasing risk scores were associated with worse scores in the three proxies across the whole group (p≤0.001).

CONCLUSIONS:

PREDICT-PD is the first study to systematically combine risk factors for PD in the general population. Validity to predict risk of PD will be tested through longitudinal follow-up of incident PD diagnosis.

Outcomes of rotigotine clinical trials: effects on motor and nonmotor symptoms of Parkinson's disease

Neurol Clin. 2013 Aug;31(3 Suppl):S51-9. doi: 10.1016/j.ncl.2013.04.011. Epub 2013 Jun 14.

Lyons KE, Pahwa R.

Source

Department of Neurology, University of Kansas Medical Center, 3599 Rainbow Boulevard, MS 2012, Kansas City, KS 66160, USA.

Abstract

Rotigotine transdermal system is a nonergot, 24-hour dopamine agonist approved for the treatment of early and advanced Parkinson's disease (PD). Recent studies have demonstrated significant improvements with rotigotine in motor function in early PD and significant improvements in daily off-time and motor function in advanced PD. In addition to motor improvements, nonmotor symptoms have been shown to be improved with rotigotine in both early and advanced PD. Rotigotine has been shown in large, controlled studies to be safe and efficacious for the treatment of motor and some nonmotor symptoms of early and advanced PD.

Inhaled Apomorphine in Patients with 'on-off' Fluctuations: A Randomized, Double-blind, Placebo-controlled, Clinic and Home Based, Parallel-group Study

J Parkinsons Dis. 2013;3(1):31-7. doi: 10.3233/JPD-120142.

Grosset KA, Malek N, Morgan F, Grosset DG.

Source

Department of Neurology, Institute of Neurological Sciences, Southern General Hospital, Glasgow.

Abstract

Background: In later stages of Parkinson's disease, treatment of 'off' periods with subcutaneous apomorphine is helpful but requires injection; inhaled apomorphine would be potentially more convenient. Objectives: To identify optimal efficacy, safety and tolerability for inhaled apomorphine in reversing Parkinson's disease 'off' periods. Methods: A randomized, double-blind, 2:1 active:placebo, parallel-group, ascending dose titration study was conducted at 16 centres in 3 countries. Inhaled apomorphine was administered under observation, at escalating fine particle doses of 1.5, 2.5, 3.5 and 4.5 mg. This was followed by at-home patient self-treatment for 2 to 4 weeks, assessed from 'on-off' diaries. Results: In 55 patients, mean age 65.6 years (range 47-79), mean disease duration 12 years (range 5-22), the mean improvement in the unified PD rating scale part 3 (UPDRS 3) was significantly greater for apomorphine (mean dose 2.3 mg) at 19.5 (standard deviation 13.6) than for placebo at 9.9 (9.6), least squares mean difference 8.4 (95% confidence interval 1.2 to 15.5, p = 0.023). During at-home testing, mean 'off' time per day was reduced by 139.8 minutes (standard deviation 149.6) for apomorphine versus 68.0 (108.6) minutes for placebo, least squares mean difference not significant at 100.5 minutes (95% confidence interval -12.0 to 212.9, p = 0.078). The onset of action was faster for apomorphine (mean 8.1 SD 6.2 minutes) than placebo (mean 13.1 SD 6.6 minutes) (p < 0.0001). Reversal of 'off' episodes was significantly more likely for episodes treated with apomorphine than those treated with placebo: apomorphine 64.6% SD 32.3 of episodes versus placebo 11.1% SD 15.3 (p < 0.0001). During at-home treatment, 36% of apomorphine and 20% of placebo patients experienced adverse events. Conclusions: Inhaled apomorphine in the dose range 1.5 to 4.5 mg, significantly improved UPDRS 3 scores in the clinic, and aborted a greater proportion of 'off' periods at-home, compared to placebo. However, daily 'off' time was not significantly reduced by the use of inhaled apomorphine.

Research on the Pre-Motor Symptoms of Parkinson's Disease: Clinical and Etiological Implications

Environ Health Perspect. 2013 Aug 9. [Epub ahead of print]

Chen H, Burton EA, Ross GW, Huang X, Savica R, Abbott RD, Ascherio A, Caviness JN, Gao X, Gray KA, Hong JS, Kamel F, Jennings D, Kirshner A, Lawler C, Liu R, Miller GW, Nussbaum R, Peddada SD, Comstock Rick A, Ritz B, Siderowf AD, Tanner CM, Tröster AI, Zhang J.

Source

National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA.

Abstract

BACKGROUND:

The etiology and natural history of Parkinson's disease (PD) are not well understood. Some non-motor symptoms such as hyposmia, rapid eye movement sleep behavior disorder, and constipation may develop during the prodromal stage of PD and precede PD diagnosis by years.

OBJECTIVES:

To discuss the promise and pitfalls of research on pre-motor symptoms of PD and to develop priorities and strategies to understand their clinical and etiological implications.

METHODS:

This review was based on a workshop held on June 7-8, 2012 at the National Institute of Environmental Health Sciences.

DISCUSSION:

Research on pre-motor symptoms of PD may offer an excellent opportunity to characterize higher-risk populations and to better understand PD etiology. Such research may lead to evaluation of novel etiological hypotheses such as the possibility that environmental toxicants or viruses may initiate PD pathogenesis in the gastrointestinal tract or olfactory bulb. At present, our understanding of pre-motor symptoms of PD is in its infancy and faces many obstacles. These symptoms are often not specific to PD and have low positive predictive value for early PD diagnosis. Further, the pathological bases and biological mechanisms of these pre-motor symptoms and their relevance to PD pathogenesis are poorly understood.

CONCLUSION:

This is an emerging research area with important data gaps to be filled. Future research is needed to understand the prevalence of multiple pre-motor symptoms and their etiological relevance to PD. Animal experiments and mechanistic studies will help understand the biology of these non-motor symptoms and test novel etiological hypothesis.

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.

"PSP is one of the atypical Parkinsonian disorders..."

"... It is often confused with Parkinson's disease but has some key features which make it different. Like people with Parkinson's disease, those with PSP are in desperate need of treatments that can help ease their suffering and ultimately offer a cure."

"This is an short film about what life is like for patients with PSP and those that care for them."

- Alastair Noyce

Risk factors for dementia with Lewy bodies: A case-control study

Neurology. 2013 Jul 26. [Epub ahead of print]

Boot BP, Orr CF, Ahlskog JE, Ferman TJ, Roberts R, Pankratz VS, Dickson DW, Parisi J, Aakre JA, Geda YE, Knopman DS, Petersen RC, Boeve BF.

Source

From the Departments of Neurology (B.P.B, C.F.O., J.E.A., Y.E.G., D.S.K., R.C.P., B.F.B.), Psychiatry and Psychology (T.J.F., Y.E.G.), Health Sciences Research (R.R., V.S.P., J.A.A., Y.E.G.), Anatomic Pathology (D.W.D.), and Robert H. and Clarice Smith and Abigail Van Buren Alzheimer's Disease Research Program of the Mayo Foundation (B.P.B., C.F.O., Y.E.G., D.S.K., R.C.P., B.F.B.), Mayo Clinic College of Medicine, Rochester MN, Scottsdale, AZ, and Jacksonville FL. B.P.B. is currently affiliated with the Neurology Department, Brigham and Women's Hospital, Boston, MA. C.F.O. is currently affiliated with Macquarie Neurology, Macquarie University Hospital, NSW, Australia.

Abstract

OBJECTIVE:

To determine the risk factors associated with dementia with Lewy bodies (DLB).

METHODS:

We identified 147 subjects with DLB and sampled 2 sex- and age-matched cognitively normal control subjects for each case. We also identified an unmatched comparison group of 236 subjects with Alzheimer disease (AD). We evaluated 19 candidate risk factors in the study cohort.

RESULTS:

Compared with controls, subjects with DLB were more likely to have a history of anxiety (odds ratio; 95% confidence interval) (7.4; 3.5-16; p < 0.0001), depression (6.0; 3.7-9.5; p < 0.0001), stroke (2.8; 1.3-6.3; p = 0.01), a family history of Parkinson disease (PD) (4.6; 2.5-8.6; p < 0.0001), and carry APOE ε4 alleles (2.2; 1.5-3.3; p < 0.0001), but less likely to have had cancer (0.44; 0.27-0.70; p = 0.0006) or use caffeine (0.29; 0.14-0.57; p < 0.0001) with a similar trend for alcohol (0.65; 0.42-1.0; p = 0.0501). Compared with subjects with AD, subjects with DLB were younger (72.5 vs 74.9 years, p = 0.021) and more likely to be male (odds ratio; 95% confidence interval) (5.3; 3.3-8.5; p < 0.0001), have a history of depression (4.3; 2.4-7.5; p < 0.0001), be more educated (2.5; 1.1-5.6; p = 0.031), have a positive family history of PD (5.0; 2.4-10; p < 0.0001), have no APOE ε4 alleles (0.61; 0.40-0.93; p = 0.02), and to have had an oophorectomy before age 45 years (7.6; 1.5-39; p = 0.015).

CONCLUSION:

DLB risk factors are an amalgam of those for AD and PD. Smoking and education, which have opposing risk effects on AD and PD, are not risk factors for DLB; however, depression and low caffeine intake, both risk factors for AD and PD, increase risk of DLB more strongly than in either.

Epidemiology of dementia with Lewy bodies--the Alzheimer-Parkinson overlap

Neurology. 2013 Jul 26. [Epub ahead of print]

Postuma RB.

Abstract

Dementia with Lewy bodies (DLB) is viewed by many as a condition that combines features of Alzheimer disease (AD) and Parkinson disease (PD). Autopsy in DLB discloses both amyloid and synuclein deposition, and the relative degree of each may determine the clinical phenotype.1 Despite being the second most common form of dementia, risk factors of DLB have never been systematically studied. The current report by Boot et al.2 therefore represents a considerable advance. Relying on data from 3 separate cohorts, the authors found that the risk factor profile of DLB appeared to combine aspects of AD and PD. Known risk factors for PD, such as nonuse of caffeine, anxiety, depression, and family history of PD were present in DLB. Similarly, AD risk factors such as APOE status, depression, and stroke were also present in DLB. Smoking, a protective factor for PD and a risk factor for AD, was not associated with DLB, perhaps suggesting that the risk factors "canceled out." However, when risk factors were common between conditions (depression and caffeine use), the relationship in DLB appeared to be stronger than for AD or PD individually, suggesting additive risks. Although the risk factors were not always comprehensively assessed and diagnosis was clinical in the majority of cases (albeit with broadly similar results in the subgroup with autopsy confirmation), the study is well-designed and comprehensively analyzed. In addition to providing for the first time a broad picture of risk factors for DLB, the study reinforces the close interactions among DLB, PD, and AD, and points to the potential importance of multiple interacting pathologies in determining clinical disease.

Surgical treatment of Parkinson disease: past, present, and future

Neurol Clin. 2013 Aug;31(3):799-808. doi: 10.1016/j.ncl.2013.03.007. Epub 2013 Apr 4.

Duker AP, Espay AJ.

Source

Department of Neurology and Rehabilitation Medicine, James J. and Joan A. Gardner Center for Parkinson's Disease and Movement Disorders, University of Cincinnati Neuroscience Institute, University of Cincinnati, 260 Stetson Street, Suite 2300, Cincinnati, OH 45267-0525, USA.

Abstract

Advances in functional neurosurgery have expanded the treatment of Parkinson disease (PD) to targeted electrical stimulation of specific nodes in the basal ganglia circuitry. Deep brain stimulation (DBS), applied to selected patients and difficult-to-manage motor fluctuations, yields substantial reductions in off time and dyskinesia. Emerging concepts in DBS include examination of new targets, such as the potential efficacy of pedunculopontine nucleus stimulation for treatment of freezing and falls, the use of pathologic oscillations in the beta band to construct an adaptive "closed-loop" DBS, and new technologies, including segmented electrodes to steer current toward specific neural populations.

Cognitive impairment and PD patients' capacity to consent to research

Neurology. 2013 Jul 26. [Epub ahead of print]

Karlawish J, Cary M, Moelter ST, Siderowf A, Sullo E, Xie S, Weintraub D.

Source

From the University of Pennsylvania (J.K., M.C., E.S., S.X., D.W.), Department of Medicine (J.K., E.S.), Department of Medical Ethics and Health Policy (J.K.), Alzheimer's Disease Center (J.K.), Neurodegenerative Disease Ethics and Policy Program (J.K., E.S.), Leonard Davis Institute of Health Economics (J.K.), Center for Clinical Epidemiology and Biostatistics (M.C., S.X.), Department of Psychiatry (D.W.), Parkinson's Disease (D.W.) and Mental Illness (D.W.) Research, Education and Clinical Centers; University of the Sciences in Philadelphia (S.T.M.); and Avid Radiopharmaceuticals (A.S.), Philadelphia, PA.

Abstract

OBJECTIVE:

To examine how cognitive impairment affects Parkinson disease (PD) patients' research consent capacity.

METHODS:

A cross-sectional study of 90 patients with PD, divided using Mattis Dementia Rating Scale-2 scores into 3 groups of 30 (normal, borderline, and impaired), and 30 neurologically normal older adults completed 2 capacity interviews (an early-phase randomized and controlled drug trial and a sham-controlled surgical implantation of genetic tissue) using the MacArthur Competence Assessment Tool for Clinical Research. Expert clinicians used the interviews to classify the patients as either capable or not capable of providing their own informed consent. These judgments were compared with performance on the Montreal Cognitive Assessment (MoCA) and the Mini-Mental State Examination (MMSE).

RESULTS:

Cognitively normal PD patients typically scored well on the capacity measures. In contrast, patients with impaired cognition were not capable of providing their own informed consent: 17% (5/30) on the drug trial and 3% (1/30) on the surgery trial were judged capable. Patients with borderline impairment showed adequate performance on measures of appreciation and reasoning, but impaired performance on understanding the drug trial compared with normal controls and normal PD patients, and on understanding the surgery trial compared with normal controls. Sixty-seven percent (20/30) on the drug trial and 57% (17/30) on the surgery trial were judged capable of consent. Receiver operating characteristic analyses showed that the MMSE and MoCA could detect the likelihood of impaired capacity, with the MoCA demonstrating greater sensitivity.

CONCLUSIONS:

PD patients with borderline cognitive impairment have impairments in their decisional capacity. The MoCA may be useful to identify the patients at risk of impaired capacity.