Sleep Problems Are Related to a Worse Quality of Life and a Greater Non-Motor Symptoms Burden in Parkinson's Disease.

INTRODUCTION: The aim of the present study was to examine the frequency of self-reported sleep problems and their associated factors in a large cohort of PD patients. METHODS: PD patients and controls, recruited from 35 centers of Spain from the COPPADIS cohort were included in this cross-sectional study. Sleep problems were assessed by the Spanish version of the Parkinson's disease Sleep Scale version 1 (PDSS-1). An overall score below 82 or a score below 5 on at least 1 item was defined as sleep problems. RESULTS: The frequency of sleep problems was nearly double in PD patients compared to controls: 65.8% (448/681) vs 33.5% (65/206) (p < 0.0001). Mean total PDSS score was lower in PD patients than controls: 114.9 ± 28.8 vs 132.8 ± 16.3 (p < 0.0001). Quality of life (QoL) was worse in PD patients with sleep problems compared to those without: PDQ-39SI, 19.3 ± 14 vs 13 ± 11.6 (p < 0.0001); EUROHIS-QoL8, 3.7 ± 0.5 vs 3.9 ± 0.5 (p < 0.0001). Non-motor symptoms burden (NMSS; OR = 1.029; 95%CI 1.015-1.043; p < 0.0001) and impulse control behaviors (QUIP-RS; OR = 1.054; 95%CI 1.009-1.101; p = 0.018) were associated with sleep problems after adjustment for age, gender, disease duration, daily equivalent levodopa dose, H&Y, UPDRS-III, UPDRS-IV, PD-CRS, BDI-II, NPI, VAS-Pain, VAFS, FOGQ, and total number of non-antiparkinsonian treatments. CONCLUSION: Sleep problems were frequent in PD patients and were related to both a worse QoL and a greater non-motor symptoms burden in PD. These findings call for increased awareness of sleep problems in PD patients.

Depression is Associated with Impulse-compulsive Behaviors in Parkinson's disease.

BACKGROUND: Depression and impulse control disorders (ICDs) are both common in Parkinson's disease (PD) patients and their coexistence is frequent. Our aim was to determine the relationship between depression and impulsive-compulsive behaviors (ICBs) in a large cohort of PD patients. METHODS: PD patients recruited from 35 centers of Spain from the COPPADIS cohort from January 2016 to November 2017 were included in the study. The QUIP-RS (Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale) was used for screening ICDs (cutoff points: gambling ≥6, buying ≥8, sex≥8, eating≥7) and compulsive behaviors (CBs) (cutoff points: hobbyism-punding ≥7). Mood was assessed with the BDI-II (Beck Depression Inventory - II) and major, minor, and subthreshold depression were defined. RESULTS: Depression was more frequent in PD patients with ICBs than in those without: 66.3% (69/104) vs 47.5% (242/509); p<0.0001. Major depression was more frequent in this group as well: 22.1% [23/104] vs 14.5% [74/509]; p=0.041. Considering types of ICBs individually, depression was more frequent in patients with pathological gambling (88.9% [8/9] vs 50.2% [303/603]; p=0.021), compulsive eating behavior (65.9% [27/41] vs 49.7% [284/572]; p=0.032), and hobbyism-punding (69% [29/42] vs 49.4% [282/571]; p=0.010) than in those without, respectively. The presence of ICBs was also associated with depression (OR=1.831; 95%CI 1.048-3.201; p=0.034) after adjusting for age, sex, civil status, disease duration, equivalent daily levodopa dose, antidepressant treatment, Hoehn&Yahr stage, non-motor symptoms burden, autonomy for activities of daily living, and global perception of QoL. LIMITATIONS: Cross-sectional design. CONCLUSIONS: Depression is associated with ICBs in PD. Specifically, with pathological gambling, compulsive eating behavior, and hobbyism-punding.

Minor hallucinations reflect early gray matter loss and predict subjective cognitive decline in Parkinson's disease.

BACKGROUND AND PURPOSE: Well-structured hallucinations in Parkinson's disease (PD) are associated with poor prognosis and dementia. However, the predictive value of minor psychotic phenomena in cognitive deterioration is not well known. Cross-sectional studies have shown that PD patients with minor hallucinations have more severe cortical atrophy than non-hallucinators, but baseline and longitudinal studies addressing the evolution of these brain differences are lacking. The impact of developing minor hallucinations on cognitive impairment and cortical atrophy progression in early PD was explored. METHODS: One hundred and thirty-one de novo PD patients from the Parkinson's Progression Marker Initiative for whom brain magnetic resonance imaging scans were available were included. Cognitive outcome at 5 years was compared between patients with and without minor hallucinations during follow-up. Additionally, using gray matter volume (GMV) voxel-based morphometry, cross-sectional (at baseline) and longitudinal (1- and 2-year GMV loss) structural brain differences between groups were studied. RESULTS: During follow-up, 35.1% of patients developed minor hallucinations. At 5 years, these patients showed an increased prevalence of subjective cognitive decline compared to non-hallucinators (44.1% vs. 13.9%; p < 0.001), but not formal cognitive impairment. Additionally, compared to non-hallucinators, they exhibited reduced GMV at baseline in visuoperceptive areas and increased GMV loss in left temporal areas (p < 0.05 corrected). CONCLUSIONS: Minor hallucinations seem to be an early clinical marker of increased neurodegeneration and are associated with mid-term subjective cognitive decline. Longer follow-up analyses would be needed to further define if these findings could reflect a higher risk of future cognitive deterioration.

Non-motor symptom burden in patients with Parkinson's disease with impulse control disorders and compulsive behaviours: results from the COPPADIS cohort.

The study was aimed at analysing the frequency of impulse control disorders (ICDs) and compulsive behaviours (CBs) in patients with Parkinson's disease (PD) and in control subjects (CS) as well as the relationship between ICDs/CBs and motor, nonmotor features and dopaminergic treatment in PD patients. Data came from COPPADIS-2015, an observational, descriptive, nationwide (Spain) study. We used the validated Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) for ICD/CB screening. The association between demographic data and ICDs/CBs was analyzed in both groups. In PD, this relationship was evaluated using clinical features and treatment-related data. As result, 613 PD patients (mean age 62.47 ± 9.09 years, 59.87% men) and 179 CS (mean age 60.84 ± 8.33 years, 47.48% men) were included. ICDs and CBs were more frequent in PD (ICDs 12.7% vs. 1.6%, p < 0.001; CBs 7.18% vs. 1.67%, p = 0.01). PD patients had more frequent previous ICDs history, premorbid impulsive personality and antidepressant treatment (p < 0.05) compared with CS. In PD, patients with ICDs/CBs presented younger age at disease onset, more frequent history of previous ICDs and premorbid personality (p < 0.05), as well as higher comorbidity with nonmotor symptoms, including depression and poor quality of life. Treatment with dopamine agonists increased the risk of ICDs/CBs, being dose dependent (p < 0.05). As conclusions, ICDs and CBs were more frequent in patients with PD than in CS. More nonmotor symptoms were present in patients with PD who had ICDs/CBs compared with those without. Dopamine agonists have a prominent effect on ICDs/CBs, which could be influenced by dose.

Differential levels of Neurofilament Light protein in cerebrospinal fluid in patients with a wide range of neurodegenerative disorders.

Cerebrospinal fluid (CSF) biomarkers are useful in the diagnosis and the prediction of progression of several neurodegenerative diseases. Among them, CSF neurofilament light (NfL) protein has particular interest, as its levels reflect neuroaxonal degeneration, a common feature in various neurodegenerative diseases. In the present study, we analyzed NfL levels in the CSF of 535 participants of the SPIN (Sant Pau Initiative on Neurodegeneration) cohort including cognitively normal participants, patients with Alzheimer disease (AD), Down syndrome (DS), frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). We evaluated the differences in CSF NfL accross groups and its association with other CSF biomarkers and with cognitive scales. All neurogenerative diseases showed increased levels of CSF NfL, with the highest levels in patients with ALS, FTD, CBS and PSP. Furthermore, we found an association of CSF NfL levels with cognitive impairment in patients within the AD and FTD spectrum and with AD pathology in DLB and DS patients. These results have implications for the use of NfL as a marker in neurodegenerative diseases.

Measuring impulsivity in Parkinson's disease: a correlational and structural neuroimaging study using different tests.

BACKGROUND AND PURPOSE: Impulsivity is an aspect of personality and a major component of multiple neuropsychiatric conditions. In Parkinson's disease, it has been associated with the expression of impulse control disorders, a highly prevalent non-motor complication. Even though multiple tests of impulsivity have been used in this context, the impact of test choice has not been addressed. The aim was to evaluate whether different impulsivity measures in Parkinson's disease share substantial inter-scale and anatomical correlations or rather mirror different underlying phenomena. METHODS: In a consecutive sample of 89 Parkinson's disease patients without impulse control disorders, four common tests were evaluated assessing different aspects of impulsivity: impulsiveness trait, decisions under implicit risk with and without losses, and delay discounting. Correlations among test scores were analysed and each score was used as a regressor in a set of grey matter volume (GMV) voxel-based morphometry analyses to explore their brain structural correlates. RESULTS: No significant correlations were found between the different impulsivity tests. Furthermore, their structural brain correlates were divergent. Impulsiveness trait appeared to be associated with lower GMV in dorsal-lateral prefrontal cortices, implicit risk (with losses) with higher GMV in the left nucleus accumbens and lower left insular GMV, implicit risk (without losses) with higher GMV in the left lingual gyrus and lower GMV in the gyri recti and delay discounting with higher GMV in the left nucleus accumbens. CONCLUSIONS: In Parkinson's disease, different impulsivity measures reflect very dissimilar behavioural and brain structural correlates. Our results suggest that parkinsonian impulsivity is not a unitary phenomenon but rather a heterogeneous entity.

[Safinamide from daily clinical practice: first clinical steps]. / Safinamida desde la practica clinica diaria: primeros pasos clinicos.

INTRODUCTION: The management of motor complications in Parkinson's disease (PD) is still limited. Safinamide, a new drug that has MAO-B inhibition and antiglutamatergic effects through inhibition of sodium channels, has shown efficacy for the treatment of fluctuations at doses of 50-100 mg/day. PATIENTS AND METHODS: From daily clinical practice, we describe the efficacy and tolerability of safinamide at three months in PD patients with motor complications. Efficacy was assessed by the Clinical Global Impression of Change scale and change in 'off' time during the daytime. All reported adverse events were recorded. RESULTS: Fifty patients were recruited. 57.4% reported to be much better or moderately better at three months, improving both motor and non-motor fluctuations. Significant decrease of 0.9 ± 0.6 h/day was achieved at three months. In 13 patients (27.6%), levodopa equivalent daily dose was reduced in 132 mg/day. In patients with dyskinesias, safinamide 100 mg/day was better for controlling fluctuations and dyskinesias. 19% of patients had mild adverse events. Seven patients stopped treatment after development of confusional syndrome. CONCLUSIONS: The dopaminergic and non-dopaminergic action of safinamide exerts a good control of motor fluctuations. In patients with fluctuations and dyskinesias the dose of 100 mg/day of safinamide is preferred. Tolerability was good, except for patients older than 75 years or in advanced stages of the disease.

TITLE: Safinamida desde la practica clinica diaria: primeros pasos clinicos.Introduccion. El tratamiento de complicaciones motoras en la enfermedad de Parkinson (EP) sigue siendo limitado. La safinamida, un nuevo farmaco con actividad inhibidora de la monoaminooxidasa-B y antiglutamatergica al inhibir canales de sodio, ha mostrado eficacia en dosis de 50-100 mg/dia para las fluctuaciones en la EP. Pacientes y metodos. Desde la practica clinica diaria, se ha descrito la eficacia y la tolerabilidad de la safinamida a los tres meses en pacientes con EP y complicaciones motoras. Se evaluo la eficacia mediante la escala global de impresion de cambio y el cambio en el numero de horas en off al dia, y se registraron todos los efectos secundarios comunicados por los pacientes. Resultados. En una muestra de 50 pacientes, el 57,4% refirio estar mucho mejor o moderadamente mejor a los tres meses, y presentaba mejoria de las fluctuaciones motoras y no motoras. El tiempo off diario disminuyo significativamente (0,9 ± 0,6 h). En 13 pacientes (27,6%) se redujo la dosis equivalente de levodopa en 132 mg/dia. En pacientes con discinesias, la dosis de 100 mg/dia consiguio un mejor control de las complicaciones motoras. El 19% de los pacientes presento efectos secundarios leves. Siete pacientes abandonaron el tratamiento por sindrome confusional. Conclusiones. El mecanismo de accion dopaminergico y no dopaminergico de la safinamida permite un buen control de las fluctuaciones en la EP. La presencia de discinesias aconseja usar la safinamida en dosis de 100 mg/dia. La safinamida presenta buena tolerabilidad global, pero debe administrarse con cautela en pacientes mayores de 75 años o estadios mas avanzados de la enfermedad.

[Myths and evidence on the use of botulinum toxin: spasticity in adults and in children with cerebral palsy]. / Mitos y evidencias en el empleo de la toxina botulinica: espasticidad del adulto y del nintilde;o con paralisis cerebral.

INTRODUCTION: Spasticity is a medical problem with a high incidence that significantly impact on the quality of life of patients and their families. AIM: To analyze and to answer different questions about the use of botulinum toxin type A (BTA) in our clinical practice. DEVELOPMENT: A group of experts in neurology develop a list of topics related with the use of BTA. Two big groups were considered: spasticity in adults and in children with cerebral palsy. A literature search at PubMed for English, French, and Spanish language articles published up to June 2016 was performed. The manuscript was structured as a questionnaire that includes those questions that, according to the panel opinion, could generate more controversy or doubt. The initial draft was reviewed by the expert panel members to allow for modifications, and after subsequent revisions for achieving the highest degree of consensus, the final text was then validated. Different questions about diverse aspects of spasticity in adults, such as methods for evaluating spasticity, infiltration techniques, doses, number of infiltration points, etc. Regarding spasticity in children with cerebral palsy, the document included questions about minimum age of infiltration, methods of analgesia, etc. CONCLUSIONS: This review is a tool for continuous training for neurologist and rehabilitation specialist and residents of both specialties, about different specific areas of the management of BTA.

TITLE: Mitos y evidencias en el empleo de la toxina botulinica: espasticidad del adulto y del nintilde;o con paralisis cerebral.Introduccion. La espasticidad es un problema medico frecuente que impacta de forma significativa en la calidad de vida de los pacientes y sus familias. Objetivo. Analizar y dar respuesta a diferentes cuestiones en el uso de la toxina botulinica tipo A (TBA) en nuestra practica clinica habitual. Desarrollo. Un grupo de expertos en neurologia elaboro una lista de temas relacionados con el uso de la TBA. Se consideraron dos grandes bloques: espasticidad del adulto y del nintilde;o con paralisis cerebral. Se realizo una revision de la bibliografia que incluyo los diferentes articulos publicados en espantilde;ol, ingles y frances hasta junio de 2016. El documento se estructuro como un cuestionario que incluyo las preguntas que, segun el criterio del panel, podrian generar mayor controversia o duda. El borrador inicial del documento fue revisado por los miembros del panel y se realizaron las modificaciones necesarias hasta alcanzar el mayor grado de consenso. A continuacion, el texto final fue validado. Se incluyeron diferentes preguntas sobre diferentes aspectos de la espasticidad en adultos: evaluacion de la espasticidad, tecnicas de infiltracion, dosis, numero de puntos, etc. En cuanto a la espasticidad en los nintilde;os con paralisis cerebral, se analizaron preguntas como: edad minima de infiltracion, metodos de sedoanalgesia, etc. Conclusiones. Esta revision constituye una herramienta para neurologos, medicos rehabilitadores y residentes de ambas especialidades, dentro de diferentes ambitos especificos del manejo de la TBA.

Social anxiety and autism spectrum traits among adult FMR1 premutation carriers.

Behavioral symptoms and traits have been proposed as early markers in neurodegenerative diseases. The aim of this study was to evaluate social anxiety and autism in FMR1 premutation carriers using the Social Phobia Inventory (SPIN) and the Autism-Spectrum Quotient (AQ) questionnaires. Fifty-nine premutation carriers were compared with 50 controls. The SPIN test showed statistically significant differences between female but not male carriers. The AQ questionnaire found statistically significant differences between premutation carriers and controls in the total AQ as well as in the social skills and attention switching subdomains. A gender effect was only observed for the social skills subdomain. Spearman's correlation analysis revealed a moderately positive correlation with the total AQ scores as well as the social skills and communication subdomains. Our results show that fragile X-associated tremor/ataxia syndrome (FXTAS) patients have higher AQ scores. Moreover, this is the first study to find statistically significant differences between FXTAS and no-FXTAS premutation carriers in the communication and the imagination subdomains, suggesting that FXTAS patients present a broader autistic phenotype than premutation carriers without FXTAS. Based on our results, a wide range of behavioral/psychiatric traits should be included within the broader phenotypic presentation of individuals with the FMR1 premutation.

Facial Dystonia with Facial Grimacing and Vertical Gaze Palsy with "Round the Houses" Sign in a 29-Year-Old Woman.

A 29-year-old woman developed progressive dysarthria and coordination problems from the age of 15. Examination showed dysarthria, facial dystonia, bibrachial dystonia, hyperreflexia, ataxia, and emotional incontinence. Downward supranuclear gaze palsy was prominent with a "Round the Houses" sign. Magnetic resonance imaging of the brain and medulla, electroneurography, and cerebrospinal fluid were normal. A computed tomography scan showed hepatosplenomegaly. This combination of progressive neurological symptoms together with hepatosplenomegaly was suggestive of inborn error of metabolism. A bone marrow biopsy showed an increased number of macrophages with foamy content, highly suggestive of lysosomal disease. Plasmatic chitotriosidase activity and CCL18 were increased. Genetic testing showed heterozygosis for the variation c.1070C→T (p.Ser357Leu) and c.1843→T (Arg615Cys), confirming the diagnosis of Niemann-Pick type C (NPC). The "Round the Houses" sign has only been described in patients with progressive supranuclear palsy (PSP). This sign is described as an inability to produce pure vertical saccades along the midline and instead moving the eyes in a lateral arc to accomplish the movement. The observation of this sign in a patient with NPC indicates that this bedside finding is not specific for PSP, but a sign of medial longitudinal fasciculus dysfunction. The presence of facial dystonia with facial grimacing together with supranuclear gaze palsy is highly characteristic and useful for the diagnosis of NPC. NPC is an important underdiagnosed condition, given the availability of treatment and a mean diagnostic delay of 6 years.

Short-lasting episodes of prosopagnosia in Parkinson's disease.

BACKGROUND: Prosopagnosia, the selective inability to recognize known faces, has been described in Alzheimer's disease and fronto-temporal dementia but is not expected to occur in Parkinson's disease (PD). METHODS AND RESULTS: We report three PD patients who developed recurrent, paroxysmal and short-lasting episodes of prosopagnosia, before progressing to PD dementia (PDD). Hallucinations and other higher-order visual deficits - such as optic ataxia and micro/macropsia - were also seen. CONCLUSION: Progressive signs of temporal and parietal dysfunction have been suggested to herald dementia in PD. The observation of prosopagnosia and other higher-order visuoperceptive defects in the transition to dementia, reinforce the importance of posterior-cortical deficit in PD.

Gaba and serotonin molecular neuroimaging in essential tremor: a clinical correlation study.

BACKGROUND: Essential tremor is the most common movement disorder in adults, but its exact etiology and pathophysiology are still not fully understood. There is some consensus, however, about the involvement of the cerebellum and accumulating evidence points towards a dysfunction of the gabaergic system. We hypothesize that the serotonin neurotransmission system may also play a role as it does in tremor in Parkinson disease. This study aimed to investigate the association between the severity of tremor symptoms and the gabaergic and serotoninergic neurotransmission systems in essential tremor. MATERIAL AND METHODS: We measured the tremor clinical rating scale score and acquired DASB and Flumazenil PET scans in 10 patients who presented with essential tremor at different stages of clinical severity. Statistically significant correlations were sought between the scale scores and parametric binding potential images. RESULTS: The correlation analysis of cerebellar Flumazenil uptake and tremor clinical rating scale scores reached statistical significance (R2 = 0.423, p = 0.041), whereas no association was detected in the DASB scans. CONCLUSIONS: The severity of tremor correlated with the abnormalities found in GABA receptor binding, suggesting a primary gabaergic deficiency or a functional abnormality at the level of GABA(A) receptor subtypes. These results may assist in the rational development of new pharmacological treatments for essential tremor.

Evaluation of doctor/patient satisfaction with the use of the Parkinson's Disease Dementia-Short-Screen (PDD-SS): a screening test for dementia in Parkinson's disease (DIFFUSION study).

INTRODUCTION: Parkinson disease (PD) has no specific neuropsychological scales for assessing the most significant cognitive impairment in PD, which has determined the use of subjective criteria or instruments designed for other diseases, making difficult the comparison between studies or the follow-up of patients. A screening test for dementia in PD (Parkinson's Disease Dementia-Short Screen [PDD-SS]) has recently been validated. To assess the degree of satisfaction of patients and researchers through the use of PDD-SS in clinical practice. PATIENTS AND METHODS: An observational, cross-over, multicentre and national study was conducted on 471 patients with PD. The degree of patient satisfaction was measured using a questionnaire in which the items scored from 0 to 10 on a visual analogue scale (0 = strongly disagree, 10 = completely agree), while the researchers were determined on a 1-5 point Likert scale (1 = strongly disagree, 5 = completely agree). RESULTS: A total of 171 patients (36.3%) patients had dementia associated with PD according to the PDD-SS, of whom 77.3% said they were satisfied with its use. The overall measurement of researcher satisfaction was 3.6±0.6 points. Ninety per cent (n=45) of them reported an overall score >3 points in the satisfaction questionnaire. The mean values of perception of applicability, usability and reliability of PDD-SS among researchers was 3.5±0.7, 3.7±0.6 and 3.1±0.5 points, respectively. CONCLUSIONS: PD patients, as well as most of the researchers, were satisfied with the use of PDD-SS in clinical practice.

Impulse control disorders and dopaminergic treatments in Parkinson's disease.

A group of disorders sharing a failure to resist an impulse to perform a typically pleasurable activity that is finally harmful to the person or to others are known under the common denomination of impulse control disorders (ICDs). These behaviors, possibly previously neglected by lack of awareness, are increasingly reported among PD patients. Compelling evidence has stressed the relation between dopaminergic replacement and development of ICDs in PD, especially but not exclusively, with dopamine agonist therapy. Besides dopaminergic replacement, younger age, smoking habit, presence of familiar gambling problems and alcohol abuse can increase the risk. ICDs in PD may greatly affect patients and caregivers quality of life, stressing the importance of their screening. Management strategies include a careful use of dopaminergic therapy using the lowest effective doses.

Motor and mental dysfunction in mother-daughter transmitted FXTAS.

OBJECTIVES: Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neuropsychiatric degenerative disorder that occurs predominantly in male FMR1 premutation carriers. Recently, a broader FXTAS spectrum that, besides the core features of tremor and gait ataxia, also includes neuropsychiatric symptoms and neuropathy as further clinically relevant symptoms has been described among females. Herein 2 fragile X syndrome families with a mother-daughter FXTAS transmission are described in detail in order to shed more light on the female FXTAS phenotype. METHODS: Molecular characterization included CGG repeat length, X-chromosome inactivation pattern determination, as well as FMR1 mRNA and FMRP levels quantification. Neuroradiologic examination was performed by 3-T MRI. Neuropsychological assessment included global cognitive, attention, and executive prefrontal functions, verbal fluencies, verbal memory, and visuospatial perception. RESULTS: Molecular, neurologic, neuropsychiatric, psychological, cognitive, and neuroradiologic features description of 2 fragile X syndrome families with a mother-daughter FXTAS transmission in which dementia is present in both mothers. CONCLUSIONS: Although it is not yet clear to what extent FXTAS shortens lifespan, our findings show that FXTAS progresses from mild tremor and/or ataxia to disabling motor and cognitive impairment, compromising the patients' quality of life. Furthermore, our results show that FXTAS in women can also develop as a multisystem neurodegenerative disorder with central and peripheral nervous system involvement, and both motor and mental disturbances.

Mild cognitive impairment in Parkinson disease: a multicenter pooled analysis.

BACKGROUND: In studies of mild cognitive impairment (MCI) in Parkinson disease (PD), patients without dementia have reported variable prevalences and profiles of MCI, likely to be due to methodologic differences between the studies. OBJECTIVE: The objective of this study was to determine frequency and the profile of MCI in a large, multicenter cohort of well-defined patients with PD using a standardized analytic method and a common definition of MCI. METHODS: A total of 1,346 patients with PD from 8 different cohorts were included. Standardized analysis of verbal memory, visuospatial, and attentional/executive abilities was performed. Subjects were classified as having MCI if their age- and education-corrected z score on one or more cognitive domains was at least 1.5 standard deviations below the mean of either control subjects or normative data. RESULTS: A total of 25.8% of subjects (95% confidence interval [CI] 23.5-28.2) were classified as having MCI. Memory impairment was most common (13.3%; 11.6-15.3), followed by visuospatial (11.0%; 9.4-13.0) and attention/executive ability impairment (10.1%; 8.6-11.9). Regarding cognitive profiles, 11.3% (9.7-13.1) were classified as nonamnestic single-domain MCI, 8.9% (7.0-9.9) as amnestic single-domain, 4.8% (3.8-6.1) as amnestic multiple-domain, and 1.3% (0.9-2.1) as nonamnestic multiple-domain MCI. Having MCI was associated with older age at assessment and at disease onset, male gender, depression, more severe motor symptoms, and advanced disease stage. CONCLUSIONS: MCI is common in patients with PD without dementia, affecting a range of cognitive domains, including memory, visual-spatial, and attention/executive abilities. Future studies of patients with PD with MCI need to determine risk factors for ongoing cognitive decline and assess interventions at a predementia stage.

Motor changes during sertraline treatment in depressed patients with Parkinson's disease*.

BACKGROUND: Pharmacological interventions to treat depressive symptoms associated with Parkinson's disease (PD) are limited. Whether selective serotonine re-uptake inhibitors increase parkinsonism or have clinically significant interactions with antiparkinsonian drugs is unresolved. PURPOSE: We used a naturalistic approach to prospectively investigate the long-term effects on motor status of adding sertraline in a large sample of community-dwelling PD patients with depressive symptoms. METHODS: Main outcome measure was the motor part of the Unified PD Rating Scale (UPDRS) at baseline and at 1-, 3-, and 6-month follow-up. Secondary measures were the change in antiparkinsonian drugs expressed as total levodopa equivalent dose and the scores of the Hospital Anxiety and Depression Scale (HADS). Of the 374 patients included, 310 (82%) completed the study. RESULTS: Treatment with sertraline (mean dose 66.0 +/- 29.8 mg) resulted in improvement in all UPDRS domains along with a significant decrease of the HADS scores. A modest but significant increase of the total dose of levodopa, without significant change of total levodopa equivalent dose, was observed. Almost 8% of patients discontinued medication for adverse events, mainly related to the gastrointestinal system. CONCLUSIONS: Although worsening of tremor was observed in some patients, active management of depression with sertraline appears to have a positive impact on parkinsonism.