The midbrain to pons ratio: A simple and specific MRI sign of progressive supranuclear palsy

Neurology. 2013 Apr 24. [Epub ahead of print]

Massey LA, Jäger HR, Paviour DC, O'Sullivan SS, Ling H, Williams DR, Kallis C, Holton J, Revesz T, Burn DJ, Yousry T, Lees AJ, Fox NC, Micallef C.

Source

From the Sara Koe PSP Research Centre (L.A.M., D.C.P., S.S.O., H.L., J.H., T.R., A.J.L.), Rita Lila Weston Institute for Neurology Studies and Queen Square Brain Bank, Department of Molecular Neurosciences, UCL Institute of Neurology, London, UK; Department of Brain Repair and Rehabilitation (H.R.J., T.Y., C.M.), UCL Institute of Neurology and Lysholm Department of Neuroradiology, National Hospital for Neurology and Neurosurgery, Queen Square, London; Dementia Research Centre (N.C.F.), UCL Institute of Neurology, London; Van Cleef Roet Centre for Nervous Diseases (D.R.W.), Monash University, Melbourne, Australia; Forensic Psychiatry Research Unit (C.K.), Queen Mary, University of London; and Institute for Ageing and Health (D.J.B.), Newcastle University, Newcastle upon Tyne, UK.

Abstract

OBJECTIVES:

MRI-based measurements used to diagnose progressive supranuclear palsy (PSP) typically lack pathologic verification and are not easy to use routinely. We aimed to develop in histologically proven disease a simple measure of the midbrain and pons on sagittal MRI to identify PSP.

METHODS:

Measurements of the midbrain and pontine base on midsagittal T1-weighted MRI were performed in confirmed PSP (n = 12), Parkinson disease (n = 2), and multiple system atrophy (MSA) (n = 7), and in controls (n = 8). Using receiver operating characteristic curve analysis, cutoff values were applied to a clinically diagnosed cohort of 62 subjects that included PSP (n = 21), Parkinson disease (n = 10), MSA (n = 10), and controls (n = 21).

RESULTS:

The mean midbrain measurement of 8.1 mm was reduced in PSP (p < 0.001) with reduction in the midbrain to pons ratio (PSP smaller than MSA; p < 0.001). In controls, the mean midbrain ratio was approximately two-thirds of the pontine base, in PSP it was <52%, and in MSA the ratio was greater than two-thirds. A midbrain measurement of <9.35 mm and ratio of 0.52 had 100% specificity for PSP. In the clinically defined group, 19 of 21 PSP cases (90.5%) had a midbrain measurement of <9.35 mm.

CONCLUSIONS:

We have developed a simple and reliable measurement in pathologically confirmed disease based on the topography of atrophy in PSP with high sensitivity and specificity that may be a useful tool in the clinic.

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"Sleep benefit" in Parkinson's disease: A systematic review

Parkinsonism Relat Disord. 2013 Apr 21. pii: S1353-8020(13)00130-2. doi: 10.1016/j.parkreldis.2013.03.014. [Epub ahead of print]

van Gilst MM, Bloem BR, Overeem S.

Source

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

Abstract

Sleep disorders are common among patients with Parkinson's disease (PD). However, there are also reports of PD patients experiencing a beneficial effect of sleep. Upon awaking in the morning some patients experience good mobility, as if they are in an "on" state induced by medication, contrary to what would be expected after a night without medication. This intriguing phenomenon is known as sleep benefit. Here, we review the available research on sleep benefit in PD, describing its prevalence, clinical effects and determinants. We also discuss the possible mechanisms underlying sleep benefit, and the potential clinical applicability. Finally, we propose a new definition of sleep benefit to allow for improved standardization and homogeneity in future research. Important research targets include the development of objective measures of sleep benefit, as a basis for obtaining a better understanding of sleep benefit, its underlying mechanisms and its potential therapeutic application.

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Diagnostic accuracy of apparent diffusion coefficient and (123)i-metaiodobenzylguanidine for differentiation of multiple system atrophy and Parkinson's disease

PLoS One. 2013 Apr 17;8(4):e61066. doi: 10.1371/journal.pone.0061066. Print 2013.

Umemura A, Oeda T, Hayashi R, Tomita S, Kohsaka M, Yamamoto K, Sawada H.

Source

Clinical Research Center, National Hospital of Utano, Kyoto, Japan ; Department of Neurology, National Hospital of Utano, Kyoto, Japan.

Abstract

BACKGROUND:

It is often hard to differentiate Parkinson's disease (PD) and parkinsonian variant of multiple system atrophy (MSA-P), especially in the early stages. Cardiac sympathetic denervation and putaminal rarefaction are specific findings for PD and MSA-P, respectively.

PURPOSE:

We investigated diagnostic accuracy of putaminal apparent diffusion coefficient (ADC) test for MSA-P and (123)I-metaiodobenzylguanidine (MIBG) scintigram for PD, especially in early-stage patients.

METHODS:

The referral standard diagnosis of PD and MSA-P were the diagnostic criteria of the United Kingdom Parkinson's Disease Society Brain Bank Criteria and the second consensus criteria, respectively. Based on the referral standard criteria, diagnostic accuracy [area under the receiver-operator characteristic curve (AUC), sensitivity and specificity] of the ADC and MIBG tests was estimated retrospectively. Diagnostic accuracy of these tests performed within 3 years of symptom onset was also investigated.

RESULTS:

ADC and MIBG tests were performed on 138 patients (20 MSA and 118 PD). AUC was 0.95 and 0.83 for the ADC and MIBG tests, respectively. Sensitivity and specificity were 85.0% and 89.0% for MSA-P diagnosis by ADC test and 67.0% and 80.0% for PD diagnosis by MIBG test. When these tests were restricted to patients with disease duration ≤3 years, the sensitivity and specificity were 75.0% and 91.4% for the ADC test (MSA-P diagnosis) and 47.7% and 92.3% for the MIBG test (PD diagnosis).

CONCLUSIONS:

Both tests were useful in differentiating between PD and MSA-P, even in the early stages. In early-stage patients, elevated putaminal ADC was a diagnostic marker for MSA-P. Despite high specificity of the MIBG test, careful neurological history and examinations were required for PD diagnosis because of possible false-negative results.

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Dopamine dysregulation syndrome in Parkinson's disease: from clinical and neuropsychological characterisation to management and long-term outcome

J Neurol Neurosurg Psychiatry. 2013 Apr 16. [Epub ahead of print]

Cilia R, Siri C, Canesi M, Zecchinelli AL, De Gaspari D, Natuzzi F, Tesei S, Meucci N, Mariani CB, Sacilotto G, Zini M, Ruffmann C, Pezzoli G.

 

Source

Parkinson Institute, Istituti Clinici di Perfezionamento, Milan, Italy.

 

Abstract

OBJECTIVE:

Dopamine dysregulation syndrome (DDS) refers to a compulsive pattern of dopaminergic drug misuse complicating Parkinson's disease (PD). To date, few data are available on DDS risk factors, cognitive profile and long-term outcome.

METHODS:

In this retrospective case-control study, consecutive PD outpatients fulfilling criteria for DDS were assessed over a 6-year period (2005-2011). They were compared with 70 PD cases matched for age at onset, gender and disease duration, and with 1281 subjects with motor fluctuations and dyskinesias. DDS patients and matched controls underwent extensive neuropsychological assessment. Strategies for DDS patients management and the outcome at the last follow-up visit were recorded.

RESULTS:

Thirty-five patients with DDS were identified, reporting history of depression, family history of PD and drug abuse, greater difference between 'Off' versus 'On' motor symptoms compared to age-matched controls. They had younger age at onset (but not any gender difference) compared to general PD population. Cognitive profile of DDS did not show major abnormalities, including executive functions. DDS patients have been followed up for 3.2±2.1 years and remission was recorded in 40% of cases. Negative DDS outcome was significantly associated with poor caregiver supervision. Sustained remission occurred more commonly on clozapine and on duodenal levodopa infusion and subthalamic nucleus deep brain stimulation (STN-DBS) than on apomorphine pump treatment.

CONCLUSIONS:

Clinicians should be aware of risk factors predisposing to DDS. Duodenal levodopa infusion and, less consistently, STN-DBS were more commonly associated with DDS remission. Effective caregiving plays a key role in long-term behavioural outcome.

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Housing and Health: Very Old People with Self-Reported Parkinson's Disease versus Controls

Parkinsons Dis. 2013;2013:710839. doi: 10.1155/2013/710839. Epub 2013 Mar 26.

Nilsson MH, Haak M, Iwarsson S.

 

Source

Department of Health Sciences, Faculty of Medicine, Lund University, P.O. Box 157, 221 00 Lund, Sweden.

 

Abstract

Objectives. To explore whether aspects of housing and health among very old people with self-reported Parkinson's disease (PD) differ from matched controls. Methods. Data from the ENABLE-AGE Survey Study were used to identify people with self-reported PD (n = 20) and three matched controls/individual (n = 60). The matching criteria were age (mean = 82 years), sex, country, and type of housing. The analyses targeted problems in activities of daily living, objective and perceived aspects of housing, for example, number of environmental barriers, accessibility (i.e., person-environment fit), and usability. Results. The number of physical environmental barriers did not differ (P = 0.727) between the samples. The PD sample had more (P < 0.001) accessibility problems than controls and perceived their homes as less (P = 0.003) usable in relation to activities. They were less independent and had more functional limitations (median 5 versus 2; P < 0.001), and 70% experienced loss of stamina or poor balance. Conclusions. Due to the fact that they have more functional limitations than very old people in general, those with self-reported PD live in housing with more accessibility problems. This explorative study has implications for rehabilitation as well as societal planning, but larger studies including people with a confirmed PD diagnosis are needed.

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Frequency of non-motor symptoms in Peruvian patients with Parkinson's disease

Arq Neuropsiquiatr. 2013 Apr;71(4):216-9.

Cosentino C, Nuñez Y, Torres L.

Abstract

Introduction: Non-motor symptoms in Parkinson's disease are often not well recognized in clinical practice. Non-motor symptoms questionnaire (NMSQuest) is a simple instrument that allows patients or caregivers to report non-motor symptoms in a practical manner. Objective: We attempted to determine the prevalence of non-motor symptoms in three hundred Parkinson's disease outpatients. Results: The mean total non-motor symptoms was 12.41, ranging from 0 to 27 of a maximum of 30. At least one was present in 99.3% of patients. A progressive increase in mean total score was observed across each 5-year interval. Depression domain scored the most "positive" answers while urinary and anxiety /memory were secondly and thirdly most prevalent respectively. Conclusion: The large number of patients included in this study allowed evaluation of the occurrence of non-motor symptoms in early and advanced disease in addition to the relationship of these kinds of symptoms with progression of disease.

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A Multicenter Study of Glucocerebrosidase Mutations in Dementia With Lewy Bodies

JAMA Neurol. 2013 Apr 15:1-9. doi: 10.1001/jamaneurol.2013.1925. [Epub ahead of print]

 

Nalls MA, Duran R, Lopez G, Kurzawa-Akanbi M, McKeith IG, Chinnery PF, Morris CM, Theuns J, Crosiers D, Cras P, Engelborghs S, De Deyn PP, Van Broeckhoven C, Mann DM, Snowden J, Pickering-Brown S, Halliwell N, Davidson Y, Gibbons L, Harris J, Sheerin UM, Bras J, Hardy J, Clark L, Marder K, Honig LS, Berg D, Maetzler W, Brockmann K, Gasser T, Novellino F, Quattrone A, Annesi G, De Marco EV, Rogaeva E, Masellis M, Black SE, Bilbao JM, Foroud T, Ghetti B, Nichols WC, Pankratz N, Halliday G, Lesage S, Klebe S, Durr A, Duyckaerts C, Brice A, Giasson BI, Trojanowski JQ, Hurtig HI, Tayebi N, Landazabal C, Knight MA, Keller M, Singleton AB, Wolfsberg TG, Sidransky E.

Abstract

IMPORTANCE While mutations in glucocerebrosidase (GBA1) are associated with an increased risk for Parkinson disease (PD), it is important to establish whether such mutations are also a common risk factor for other Lewy body disorders. OBJECTIVE To establish whether GBA1 mutations are a risk factor for dementia with Lewy bodies (DLB). DESIGN We compared genotype data on patients and controls from 11 centers. Data concerning demographics, age at onset, disease duration, and clinical and pathological features were collected when available. We conducted pooled analyses using logistic regression to investigate GBA1 mutation carrier status as predicting DLB or PD with dementia status, using common control subjects as a reference group. Random-effects meta-analyses were conducted to account for additional heterogeneity. SETTING Eleven centers from sites around the world performing genotyping. PARTICIPANTS Seven hundred twenty-one cases met diagnostic criteria for DLB and 151 had PD with dementia. We compared these cases with 1962 controls from the same centers matched for age, sex, and ethnicity. MAIN OUTCOME MEASURES Frequency of GBA1 mutations in cases and controls. RESULTS We found a significant association between GBA1 mutation carrier status and DLB, with an odds ratio of 8.28 (95% CI, 4.78-14.88). The odds ratio for PD with dementia was 6.48 (95% CI, 2.53-15.37). The mean age at diagnosis of DLB was earlier in GBA1 mutation carriers than in noncarriers (63.5 vs 68.9 years; P < .001), with higher disease severity scores. CONCLUSIONS AND RELEVANCE Mutations in GBA1 are a significant risk factor for DLB. GBA1 mutations likely play an even larger role in the genetic etiology of DLB than in PD, providing insight into the role of glucocerebrosidase in Lewy body disease.

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Serial sevens - can practise make perfect?

The 'serial sevens' task, in which subjects are asked to count backwards from 100 by repeatedly subtracting 7 (e.g. 100-93-86-79-72-etc), is a commonly used test in the assessment of cognition. It is part of the standard set of tasks used to assess people for cognitive decline - the mini mental state examination (or MMSE) and is worth 5 out of the 30 available marks. Attention and memory are required to perform the task.

Dementia is common and rates will increase dramatically in the coming years. There is a strong drive towards earlier detection with a view to earlier treatment - identification of mild cognitive impairment. In parallel, public awareness of dementia or cognitive impairment has increased significantly also. Many people know or have known someone with dementia and many will have attended hospital or general practice appointments with this person. Dementia now receives greater mention in the media, both factual and fictional, than ever before. For these reasons, subjects are increasingly likely to be aware of the mental tests that will be performed if their cognition comes under assessment. The 'serial sevens' test has gained particular notoriety!

In the PREDICT-PD study we use a standard battery of cognitive tests called the Montreal Cognitive Assessment or MoCA, which like the MMSE, includes the 'serial sevens' task. It is not uncommon for our research subjects to say that they were expecting the 'serial sevens' as part of the assessment and consequently have been practising. A practised test uses different memory retrieval processes and significantly less attention; I am certain that practise improves the likelihood of scoring full marks.

Alternatives to 'serial sevens' exist and include: using a number other than seven, naming months of the year in reverse order and spelling WORLD backwards. Each of these are slightly different in terms of difficulty and it is tricky to pool data in a research setting if different tests have been used. On an individual basis, substitution of the 'serial sevens' test for an alternative is often appropriate and may yield findings that were not apparent when a practised 'serial sevens' test was performed. Nonetheless clinicians should be aware that prior knowledge of such tests, particularly ones that can be practised, may mask a subtle decline in cognition when using standardised assessments.

- Alastair Noyce

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A systematic review of biomarkers for disease progression in Parkinson's disease

BMC Neurol. 2013 Apr 12;13(1):35. [Epub ahead of print]

McGhee DJ, Royle PL, Thompson PA, Wright DE, Zajicek JP, Counsell CE.

 

Abstract

BACKGROUND:

Using surrogate biomarkers for disease progression as endpoints in neuroprotective clinical trials may help differentiate symptomatic effects of potential neuroprotective agents from true disease-modifying effects. A systematic review was undertaken to determine what biomarkers for disease progression in Parkinson's disease (PD) exist.

METHODS:

MEDLINE and EMBASE (1950--2010) were searched using five search strategies. Abstracts were assessed to identify papers meriting review in full. Studies of participants with idiopathic PD diagnosed by formal criteria or clearly described clinical means were included. We made no restriction on age, disease duration, drug treatment, or study design. We included studies which attempted to draw associations between any tests used to investigate disease progression and any clinical measures of disease progression. The electronic search was validated by hand-searching the two journals from which most included articles came.

RESULTS:

183 studies were included: 163 (89%) cross-sectional, 20 (11%) longitudinal. The electronic search strategy had a sensitivity of 71.4% (95% CI 51.1-86.0) and a specificity of 97.1% (95% CI 96.5-97.7). In longitudinal studies median follow-up was 2.0 years (IQR 1.1-3.5). Included studies were generally poor quality - cross-sectional with small numbers of participants, applying excessive inclusion/exclusion criteria, with flawed methodologies and simplistic statistical analyses.

CONCLUSION:

We found insufficient evidence to recommend the use of any biomarker for disease progression in PD clinical trials, which may simply reflect the poor quality of research in this area. We therefore present a provisional 'roadmap' for conducting future disease progression biomarker studies, and recommend new quality criteria by which future studies may be judged.

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Pharmacologic Treatment of Anxiety Disorders in Parkinson Disease

Am J Geriatr Psychiatry. 2013 Mar 29. pii: S1064-7481(12)00053-X. doi: 10.1016/j.jagp.2012.10.023. [Epub ahead of print]

Pontone GM, Williams JR, Anderson KE, Chase G, Goldstein SR, Grill S, Hirsch ES, Lehmann S, Little JT, Margolis RL, Palanci J, Rabins PV, Weiss HD, Marsh L.

Source

Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD. Electronic address: gponton1@jhmi.edu.

Abstract

OBJECTIVE:

Neither best practices nor an evidence base for the pharmacologic treatment of anxiety in Parkinson disease (PD) has been established. This study investigated pharmacologic treatment of anxiety disorders in idiopathic PD and the associated clinical features.

DESIGN:

Cross-sectional.

SETTING:

Three community-based movement disorder neurology practices.

PARTICIPANTS:

250 subjects with PD.

MEASUREMENTS:

Anxiety disorder diagnoses were established by consensus using a panel of six psychiatrists with expertise in geriatric psychiatry and movement disorders. Current medications were provided by the treating neurologists at the time of interview.

RESULTS:

Among subjects with anxiety disorders only, 53% were untreated with medications. When anxious subjects with comorbid depressive disorders were included, 70.8% were on medications effective for treatment of anxiety. Subjects with anxiety and comorbid depressive disorders were more likely to be treated for their psychiatric disturbances than subjects with anxiety disorders alone (odds ratio: 8.33), as were subjects with comorbid motor fluctuations (odds ratio: 3.65). There were no differences in the types of anti-anxiety medications used in regard to the presence of depression or motor fluctuations.

CONCLUSIONS:

These findings suggest that over half of nondepressed PD patients with clinically significant anxiety are untreated with medication. A better understanding of the role of clinical features associated with anxiety in PD, such as depression and motor fluctuations, may improve the recognition and treatment of anxiety disorders in this population.

Rasagiline ameliorates olfactory deficits in an alpha-synuclein mouse model of Parkinson's disease

PLoS One. 2013;8(4):e60691. doi: 10.1371/journal.pone.0060691. Epub 2013 Apr 3.

Petit GH, Berkovich E, Hickery M, Kallunki P, Fog K, Fitzer-Attas C, Brundin P.

Source

Neuronal Survival Unit, Wallenberg Neuroscience Center, Department of Experimental Medical Science, BMC B11, Lund University, Lund, Sweden.

Abstract

Impaired olfaction is an early pre-motor symptom of Parkinson's disease. The neuropathology underlying olfactory dysfunction in Parkinson's disease is unknown, however α-synuclein accumulation/aggregation and altered neurogenesis might play a role. We characterized olfactory deficits in a transgenic mouse model of Parkinson's disease expressing human wild-type α-synuclein under the control of the mouse α-synuclein promoter. Preliminary clinical observations suggest that rasagiline, a monoamine oxidase-B inhibitor, improves olfaction in Parkinson's disease. We therefore examined whether rasagiline ameliorates olfactory deficits in this Parkinson's disease model and investigated the role of olfactory bulb neurogenesis. α-Synuclein mice were progressively impaired in their ability to detect odors, to discriminate between odors, and exhibited alterations in short-term olfactory memory. Rasagiline treatment rescued odor detection and odor discrimination abilities. However, rasagiline did not affect short-term olfactory memory. Finally, olfactory changes were not coupled to alterations in olfactory bulb neurogenesis. We conclude that rasagiline reverses select olfactory deficits in a transgenic mouse model of Parkinson's disease. The findings correlate with preliminary clinical observations suggesting that rasagiline ameliorates olfactory deficits in Parkinson's disease.

Depressive symptoms in Parkinson's disease and in non-neurological medical illnesses

Neuropsychiatr Dis Treat. 2013;9:389-96. doi: 10.2147/NDT.S40013. Epub 2013 Mar 21.

Assogna F, Fagioli S, Cravello L, Meco G, Pierantozzi M, Stefani A, Imperiale F, Caltagirone C, Pontieri FE, Spalletta G.

Source

I.R.C.C.S. Santa Lucia Foundation, Rome, Italy.

Abstract

BACKGROUND:

Patients with neurological and non-neurological medical illnesses very often complain of depressive symptoms that are associated with cognitive and functional impairments. We compared the profile of depressive symptoms in Parkinson's disease (PD) patients with that of control subjects (CS) suffering from non-neurological medical illnesses.

METHODS:

One-hundred PD patients and 100 CS were submitted to a structured clinical interview for identification of major depressive disorder (MDD) and minor depressive disorder (MIND), according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision (DSM-IV-TR), criteria. The Hamilton Depression Rating Scale (HDRS) and the Beck Depression Inventory (BDI) were also administered to measure depression severity.

RESULTS:

When considering the whole groups, there were no differences in depressive symptom frequency between PD and CS apart from worthlessness/guilt, and changes in appetite reduced rates in PD. Further, total scores and psychic and somatic subscores of HDRS and BDI did not differ between PD and CS. After we separated PD and CS in those with MDD, MIND, and no depression (NODEP), comparing total scores and psychic/somatic subscores of HDRS and BDI, we found increased total depression severity in NODEP PD and reduced severity of the psychic symptoms of depression in MDD PD, with no differences in MIND. However, the severity of individual symptom frequency of depression was not different between PD and CS in MDD, MIND, and NODEP groups.

CONCLUSION:

Although MDD and MIND phenomenology in PD may be very similar to that of CS with non-neurological medical illnesses, neurological symptoms of PD may worsen (or confound) depression severity in patients with no formal/structured DSM-IV-TR, diagnosis of depressive mood disorders. Thus, a thorough assessment of depression in PD should take into consideration the different impacts of neurological manifestations on MDD, MIND, and NODEP.

Prevalence of Parkinson Disease and Parkinson Disease Dementia in Community Nursing Homes

Am J Geriatr Psychiatry. 2013 Jan 11. pii: S1064-7481(12)00104-2. doi: 10.1016/j.jagp.2012.12.007. [Epub ahead of print]

Hoegh M, Ibrahim AK, Chibnall J, Zaidi B, Grossberg GT.

Source

Saint Louis University School of Medicine, Saint Louis, Missouri.

Abstract

OBJECTIVE:

To estimate the prevalence of Parkinson disease (PD) and Parkinson disease dementia (PDD) in community nursing homes. To estimate how many residents who meet criteria for PDD have been diagnosed with PDD and prescribed a Federal Drug Administration (FDA)-approved treatment for PDD.

SETTING:

Three private Saint Louis metropolitan area nursing homes.

PARTICIPANTS:

Fifty-five residents with a chart diagnosis of PD from a total of 714 residents were identified. Sixteen subjects or families did not give consent and two were excluded from the study because advanced stage of the illness impaired evaluation. Thirty-seven subjects with an established diagnosis of PD participated in the study.

DESIGN AND MEASUREMENTS:

A chart review was used to identify the study sample: residents with an established diagnosis of PD. Consent was obtained from the nursing home administration, families or guardians, and the residents themselves (where applicable). Study data were obtained from review of residents' medical charts, family/caregiver interview, resident interview, resident cognitive testing (Mini-Mental State Examination, clock drawing test), and resident depression assessment (15-item Geriatric Depression Scale). Diagnosis of PDD was defined using existing literature and described below. Data were analyzed using SPSS version 15.

RESULT:

Of the 714 nursing home residents, 55 (7.7%) met criteria for PD. Of these, 37 participated in the study and 18 (48.6%) met criteria for PDD. None were diagnosed with PDD in the charts and 11.1% (2 of 18) were on FDA-approved treatment.

CONCLUSION:

In this sample of nursing home residents, the prevalence of PD was 7.7% and the overall prevalence of PDD was 3.7%. PDD remains an unrecognized entity in the nursing home setting. Close to half (48.65%) of nursing home residents with PD may have PDD at any given time and they remain undiagnosed and largely undertreated.

Determinants of delayed diagnosis in Parkinson's disease

J Neurol. 2013 Apr 10. [Epub ahead of print]

Breen DP, Evans JR, Farrell K, Brayne C, Barker RA.

Source

Centre for Brain Repair, University of Cambridge, ED Adrian Building, Forvie Site, Robinson Way, Cambridge, CB2 0PY, UK

Abstract

The early and accurate diagnosis of Parkinson's disease (PD) is the first step towards optimal patient management. The aim of this study was to investigate the major determinants of delayed diagnosis in PD. We recruited a population-representative cohort of 239 newly-diagnosed PD patients who underwent clinical and neuropsychological evaluation. Non-parametric methods were used to define the factors associated with diagnostic delay. The median time from motor symptom onset to primary care physician (PCP) presentation was considerably longer than the time from PCP presentation to PD diagnosis (11 vs. 1 months). Male sex and presenting motor phenotype were independently associated with delayed PCP presentation on Cox regression analysis. Patients presenting with gait disturbance experienced the longest delay, whilst those presenting with tremor had the shortest. In summary, male sex and presenting motor phenotype are key determinants of delayed diagnosis in PD.

Cholinesterase inhibitors for dementia with Lewy bodies, Parkinson's disease dementia and cognitive impairment in Parkinson's disease

Cochrane Database Syst Rev. 2012 Mar 14;3:CD006504. doi: 10.1002/14651858.CD006504.pub2.

Rolinski M, Fox C, Maidment I, McShane R.

Source

Oxford University Hospitals NHS Trust, John Radcliffe Hospital, Headington, Oxford, UK.

Abstract

BACKGROUND:

Previous Cochrane reviews have considered the use of cholinesterase inhibitors in both Parkinson's disease with dementia (PDD) and dementia with Lewy bodies (DLB). The clinical features of DLB and PDD have much in common and are distinguished primarily on the basis of whether or not parkinsonism precedes dementia by more than a year. Patients with both conditions have particularly severe deficits in cortical levels of the neurotransmitter acetylcholine. Therefore, blocking its breakdown using cholinesterase inhibitors may lead to clinical improvement.

OBJECTIVES:

To assess the efficacy, safety and tolerability of cholinesterase inhibitors in dementia with Lewy bodies (DLB), Parkinson's disease with dementia (PDD), and cognitive impairment in Parkinson's disease falling short of dementia (CIND-PD) (considered as separate phenomena and also grouped together as Lewy body disease).

SEARCH METHODS:

The trials were identified from a search of ALOIS, the Specialised Register of the Cochrane Dementia and Cognitive Improvement Group (on 30 August 2011) using the search terms Lewy, Parkinson, PDD, DLB, LBD. This register consists of records from major healthcare databases (MEDLINE, EMBASE, PsycINFO, CINAHL) and many ongoing trial databases and is updated regularly.Reference lists of relevant studies were searched for additional trials.

SELECTION CRITERIA:

Randomised, double-blind, placebo-controlled trials assessing the efficacy of treatment with cholinesterase inhibitors in DLB, PDD and cognitive impairment in Parkinson's disease (CIND-PD).

DATA COLLECTION AND ANALYSIS:

Data were extracted from published reports by one review author (MR). The data for each 'condition' (that is DLB, PDD or CIND-PD) were considered separately and, where possible, also pooled together. Statistical analysis was conducted using Review Manager version 5.0.

MAIN RESULTS:

Six trials met the inclusion criteria for this review, in which a total of 1236 participants were randomised. Four of the trials were of a parallel group design and two cross-over trials were included. Four of the trials included participants with a diagnosis of Parkinson's disease with dementia (Aarsland 2002a; Dubois 2007; Emre 2004; Ravina 2005), of which Dubois 2007 remains unpublished. Leroi 2004 included patients with cognitive impairment and Parkinson's disease (both with and without dementia). Patients with dementia with Lewy bodies (DLB) were included in only one of the trials (McKeith 2000).For global assessment, three trials comparing cholinesterase inhibitor treatment to placebo in PDD (Aarsland 2002a; Emre 2004; Ravina 2005) reported a difference in the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) score of -0.38, favouring the cholinesterase inhibitors (95% CI -0.56 to -0.24, P < 0.0001).For cognitive function, a pooled estimate of the effect of cholinesterase inhibitors on cognitive function measures was consistent with the presence of a therapeutic benefit (standardised mean difference (SMD) -0.34, 95% CI -0.46 to -0.23, P < 0.00001). There was evidence of a positive effect of cholinesterase inhibitors on the Mini-Mental State Examination (MMSE) in patients with PDD (WMD 1.09, 95% CI 0.45 to 1.73, P = 0.0008) and in the single PDD and CIND-PD trial (WMD 1.05, 95% CI 0.42 to 1.68, P = 0.01) but not in the single DLB trial.For behavioural disturbance, analysis of the pooled continuous data relating to behavioural disturbance rating scales favoured treatment with cholinesterase inhibitors (SMD -0.20, 95% CI -0.36 to -0.04, P = 0.01).For activities of daily living, combined data for the ADCS and the Unified Parkinson's Disease Rating Scale (UPDRS) activities of daily living rating scales favoured treatment with cholinesterase inhibitors (SMD -0.20, 95% CI -0.38 to -0.02, P = 0.03).For safety and tolerability, those taking a cholinesterase inhibitor were more likely to experience an adverse event (318/452 versus 668/842; odds ratio (OR) 1.64, 95% CI 1.26 to 2.15, P = 0.0003) and to drop out (128/465 versus 45/279; OR 1.94, 95% CI 1.33 to 2.84, P = 0.0006). Adverse events were more common amongst those taking rivastigmine (357/421 versus 173/240; OR 2.28, 95% CI 1.53 to 3.38, P < 0.0001) but not those taking donepezil (311/421 versus 145/212; OR 1.24, 95% CI 0.86 to 1.80, P = 0.25). Parkinsonian symptoms in particular tremor (64/739 versus 12/352; OR 2.71, 95% CI 1.44 to 5.09, P = 0.002), but not falls (P = 0.39), were reported more commonly in the treatment group but this did not have a significant impact on the UPDRS (total and motor) scores (P = 0.71). Fewer deaths occurred in the treatment group than in the placebo group (4/465 versus 9/279; OR 0.28, 95% CI 0.09 to 0.84, P = 0.03).

AUTHORS' CONCLUSIONS:

The currently available evidence supports the use of cholinesterase inhibitors in patients with PDD, with a positive impact on global assessment, cognitive function, behavioural disturbance and activities of daily living rating scales. The effect in DLB remains unclear. There is no current disaggregated evidence to support their use in CIND-PD.

Doxepin and cognitive behavioural therapy for insomnia in patients with Parkinson's disease - A randomized study

Parkinsonism Relat Disord. 2013 Apr 2. pii: S1353-8020(13)00119-3. doi: 10.1016/j.parkreldis.2013.03.003. [Epub ahead of print]

Rios Romenets S, Creti L, Fichten C, Bailes S, Libman E, Pelletier A, Postuma RB.

Source

Department of Neurology, McGill University, Montreal General Hospital, Montreal, Quebec, Canada.

Abstract

INTRODUCTION:

Although a variety of pharmacologic and non-pharmacologic treatments are effective for insomnia in the general population, insomnia in Parkinson's disease differs in important ways and may need different treatments. No studies have conclusively demonstrated effective insomnia treatments in Parkinson's disease.

METHODS:

We conducted a three-arm six-week randomized pilot study assessing non-pharmacologic treatment (cognitive behavioural therapy with bright light therapy) or doxepin (10 mg daily), compared to an inactive placebo in Parkinson's patients with insomnia. Sleep outcomes included insomnia scales, clinical global impression, sleep diaries and actigraphy. Secondary outcomes included motor severity, fatigue, depression and quality of life.

RESULTS:

18 patients were randomized, 6 to each group. Compared to placebo, doxepin improved the Insomnia Severity Index (-9 ± 5.4 vs. -2 ± 3.9, p = 0.03), the SCOPA-night score (-5.2 ± 1.5 vs. -2.3 ± 2.8, p = 0.049), the Pittsburgh Sleep Quality Index-sleep disturbances subscale (-0.5 ± 0.5 vs 0.2 ± 0.4, p = 0.02), and both patient and examiner-rated clinical global impression of change (1.7 ± 0.8 vs. 0.5 ± 0.8, p = 0.03 and 1.4 ± 0.5 vs. 0.3 ± 0.5, p = 0.003). On secondary outcomes doxepin reduced the fatigue severity scale (p = 0.02) and improved scores on the Montreal Cognitive Assessment (p = 0.007). Non-pharmacological treatment reduced the Insomnia Severity Index (-7.8 ± 3.8 vs. -2.0 ± 3.9, p = 0.03), and the examiner-reported clinical global impression of change (p = 0.006), but was associated with decline in Parkinson Disease Questionnaire-39. There were no changes in other primary and secondary outcomes, including actigraphy outcomes. Adverse events were comparable in all groups.

CONCLUSION:

Doxepin and non-pharmacologic treatment substantially improved insomnia in Parkinson's disease. These potential benefits must be replicated in a full confirmatory randomized controlled trial.

Discontinuities in slow finger movements in patients with Parkinson's disease

Neurosci Lett. 2013 Apr 2. pii: S0304-3940(13)00262-0. doi: 10.1016/j.neulet.2013.02.068. [Epub ahead of print]

Bettray LM, Eggers C, Quatuor EL, Florin E, Reck C, Pauls AK, Barbe MT, Fink GR, Timmermann L.

Source

Department of Neurology, University of Cologne, Cologne, Germany.

Abstract

Slow finger movements in healthy humans are characterized by discontinuous rhythmic changes in a low frequency band about 8Hz. These pulsatile changes in velocity are thought to present the central output of an oscillatory cerebello-thalamo-cortical network in the same frequency. Hypothesizing that patients with Parkinson's Disease (PD) in the dopaminergic OFF- and ON-condition show changes in the characteristics of discontinuities compared to healthy humans, we used a 3 D-ultrasound device to measure slow finger movements of 16 patients with PD and 12 age-matched controls. We provide evidence that slow finger movements of patients with PD are characterized by discontinuities in acceleration, which are significantly slower in the OFF- but not in the ON-condition compared to healthy controls. Correlation analysis between clinical motor improvement after dopaminergic medication and changes of peak frequencies and peak power of discontinuities was not significant. We conclude that the oscillatory brain network of slow finger movements is affected in PD, presenting in a lower frequency in the OFF-condition. We suggest that one factor of the modulation of this network is a dopaminergic stimulation.

Substantia nigra hyperechogenicity in healthy controls: a [18Fluoro] Dopa-PET follow-up study

J Neurol. 2013 Apr 7. [Epub ahead of print]

Schroeder U, Behnke S, Buchholz HG, Fassbender K, Schreckenberger M, Berg D.

Source

Department of Neurology, Saarland University Hospital, Kirrberger Str, 66421, Homburg/Saar, Germany.

Abstract

In order to assess nigrostriatal function over time in healthy subjects with substantia nigra hyperechogenicity (SN+) believed to be at higher risk for Parkinson's disease (PD), ten healthy SN+ subjects underwent [18Fluoro] Dopa positron emission tomography (PET) twice-at baseline and after a mean of 7.3 years. Neurological examination took place at study inclusion followed by a structured telephone interview focusing on early Parkinsonian symptoms at the time point of second PET study and 3.5 years later. The [18Fluoro] Dopa uptake remained unchanged in eight of ten participants. In the other two subjects marked unilateral reduction of putaminal [18Fluoro] Dopa uptake ratios appeared over the time, followed by complaints of a clinically manifest PD in one. We suggest that the progressive pathological PET findings in 20 % and PD conversion in 10 % of our cohort may be in accordance with the presumed proportion of SN+ individuals eventually developing PD based on SN+ prevalence of 10 % within the healthy population, being ten times higher than PD prevalence in the age of over 60 years. Our findings hint towards a significance of SN+ indicating a high risk for PD in some extrapyramidally healthy SN+ individuals.

Prodromal autonomic symptoms and signs in Parkinson's disease and dementia with Lewy bodies.

Mov Disord. 2013 Mar 28. doi: 10.1002/mds.25445. [Epub ahead of print]

Postuma RB, Gagnon JF, Pelletier A, Montplaisir J.

Source

Department of Neurology, McGill University, Montreal General Hospital, Montreal, Quebec, Canada; Centre d'Études Avancées en Médecine du Sommeil, Hôpital du Sacré-Cœur de Montréal, Montréal, Québec, Canada.

Abstract

Pathologic staging systems suggest that autonomic dysfunction may be an early manifestation of Parkinson's disease and dementia with Lewy bodies. However, direct evidence is limited, and no prospective studies have measured when autonomic dysfunction starts before disease. Patients with idiopathic rapid eye movement (REM) sleep behavior disorder are at very high risk of developing neurodegenerative synucleinopathy, providing an opportunity to directly observe the development of autonomic dysfunction from prodromal stages of neurodegeneration. Patients with idiopathic REM sleep behavior disorder were followed annually in a prospective cohort that was established in 2004. Urinary, orthostatic, erectile, and constipation symptoms and systolic blood pressure drop from lying to standing were assessed annually. Patients who eventually developed defined synucleinopathy were compared with age-matched controls. The evolution of autonomic measures was assessed with regression analysis to determine when markers first deviated from control values. Sensitivity and specificity of autonomic markers for identification of prodromal disease were calculated. Of 91 patients, 32 developed disease. In prodromal stages, there was substantial autonomic dysfunction observable at least 5 years before diagnosis. On regression analysis, autonomic dysfunction appeared to progress slowly over prodromal periods. The estimated onset of autonomic dysfunction ranged from 11 years to 20 years, and systolic drop (20.4 years) and constipation (15.3 years) had the earliest estimates. Systolic drop, erectile dysfunction, and constipation could identify disease up to 5 years before diagnosis with sensitivity ranging from 50% to 90%. By directly observing development of neurodegenerative synucleinopathy, we confirmed that autonomic dysfunction can occur early in neurodegenerative synucleinopathy, even as long as 20 years before defined disease.

The relationship between balance control and vitamin D in Parkinson's disease-a pilot study

Mov Disord. 2013 Apr 2. doi: 10.1002/mds.25405. [Epub ahead of print]

Peterson AL, Mancini M, Horak FB.

Source

Parkinson's Center of Oregon, Oregon Health and Science University, Portland, Oregon, USA; Parkinson's Disease Research and Education Center, Portland Veterans Affairs Hospital, Portland, Oregon, USA.

Abstract

BACKGROUND:

Balance problems and falls are a major source of morbidity and mortality in patients with Parkinson's disease. Vitamin D supplementation reduces falls and sway in neurologically intact elderly fallers, but effects in Parkinson's disease are not established.

METHODS:

To study this relationship and select outcome measures for a vitamin D intervention study, balance function and vitamin D concentration were quantified in a series of Parkinson's patients in a cross-sectional, observational study. Participants underwent a battery of 5 balance tests.

RESULTS:

Serum vitamin D concentrations were correlated inversely with Parkinson's severity, as measured by the motor Unified Parkinson's Disease Rating Scale. Among the balance measures, vitamin D concentrations were correlated with automatic posture responses to backwards translation, specifically with response strength and stance weight asymmetry.

CONCLUSIONS:

These findings support the hypothesis that vitamin D plays a role in balance among patients with Parkinson's disease and identify specific outcome measures for detecting effects of vitamin D upon balance.

Cognitive Change in Newly-Diagnosed Patients with Parkinson's Disease: A 5-Year Follow-up Study

J Int Neuropsychol Soc. 2013 Apr 2:1-14. [Epub ahead of print]

Broeders M, Velseboer DC, de Bie R, Speelman JD, Muslimovic D, Post B, de Haan R, Schmand B.

Source

1 Department of Brain and Cognition, University of Amsterdam, Amsterdam, the Netherlands.

Abstract

Cognitive change is frequently observed in patients with Parkinson's disease (PD). However, the exact profile and extent of cognitive impairments remain unclear due to the clinical heterogeneity of PD and methodological issues in many previous studies. In this study, we aimed to examine the severity, frequency, and profile of cognitive changes in newly diagnosed PD patients over 5 years. At baseline and after 3 and 5 years, a hospital-based sample of PD patients (n = 59) and healthy controls (n = 40) were given neuropsychological tests covering six cognitive domains. Patients showed greater decline over time than healthy controls on all cognitive domains, except for attention. The profile of decline showed that psychomotor speed and memory were most affected. At the individual level 53% of the patients showed more cognitive decline than controls. Age at onset and memory impairment at baseline predicted cognitive decline. Cognitive functions in PD patients show greater decline in most domains than in healthy elderly over the course of 5 years. Due to selection bias as a result of attrition, the actual degree of decline may be greater than reported here.