Starkstein Apathy Scale Research Articles

Apathy Induced by Subthalamic Nucleus Deep Brain Stimulation in Parkinson's Disease: A Meta-Analysis.

ABSTRACTApathy, the loss of motivation, is a common problem in Parkinson's disease (PD) and often observed following deep brain stimulation (DBS) of the subthalamic nucleus (STN). The aim of this meta‐analysis was to determine the occurrence of apathy following STN DBS in literature. Relevant articles were searched in PubMed/Medline, SCOPUS, EMBASE, and Web of Sciences electronic databases. Studies were included if they reported apathy scores pre‐ and post‐DBS or the cross‐sectional difference between PD patients receiving STN DBS and patients receiving medication only. Thirty‐three articles were included in the meta‐analyses from 6,658 screened articles by two authors independently. A total of 1,286 patients were included with a mean age (±standard deviation [SD]) of 58.4 ± 8.5 years and a disease duration of 11.0 ± 5.8 years. The apathy score measured by means of the Apathy Evaluation Scale (AES), Starkstein Apathy Scale (SAS), and the Lille Apathy Rating Scale (LARS) was significantly higher after DBS than pre‐operatively (g = 0.34, 95% confidence interval [CI] = 0.19–0.48, P < 0.001). An equal, significant difference in severity of apathy was found between STN DBS and medication only (g = 0.36, 95% CI = 0.03–0.65; P = 0.004). Statistical heterogeneity was moderately high, but the effects stood strong after multiple analyses and were independent of tapering off dopaminergic medication. The findings of this meta‐analysis indicate that apathy is increased after STN DBS compared to the pre‐operative state and to medication only (systematic review registration number: PROSPERO CRD42019133932). © 2020 Universiteit van Amsterdam. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

On the heterogeneity of depression in Parkinson’s disease

Depression in Parkinson’s disease (PD) is one of the leading manifestations of the disease, which reduces quality of life in patients.Objective: to compare the clinical features of depression at different stages of PD.Patients and methods. Examinations were made in 162 PD patients aged 62.14±1.99 years without dementia (PD duration, 5.78±0.58 years; Stage, 2.5±0.6). The Unified PD Rating Scale (UPDRS), the Beck Depression Inventory (BDI), and the Spielberger Inventory, the 16-Item PD Fatigue Scale (PFS-16), and the Starkstein Apathy Scale were examined. Dopaminergic agents (DAAs) were prescribed when movement disorders were insufficiently corrected. Antidepressants were not used during the investigation. The follow-up period was 18 months.Results and discussion. Depression was detected in 136 (84%) patients. Depression symptoms appeared in 16 (12%) patients within 1–8 years before the onset of motor symptoms (MS), in 37 (27%) in the first 2 years after the onset of MS, in 44 (32%) at Hoehn–Yahr stages 2–3 without motor fluctuations (MFs), and in 39 (29%) at the onset of MF. The most severity of depression was noted in cases of its development at the premotor stage and in the period of MF occurrence. During the follow-up, the manifestations of depression disappeared in 16% of the patients taking a DAA; these were relapsing-remitting in 9%, progressive in 11%, or remained stable in 64%. The patients with depression occurring at the premotor stage had a progressive course of depression and a low DAA efficacy: an increase in severity in 30% of cases despite therapy and a reversal in only 10% of cases (versus 25–45% of those at depression onset in the presence of MS). In cases of depression occurring in the first 2 years after MS onset, its reversal was observed in 45%; the group of patients with depression onset in the presence of MF showed a stable course with slight severity fluctuations in 77.8%.Conclusion. Depression in PD is a heterogeneous affective disorder. There is a relatively favorable course of depression when the latter occurs in the first two years of MS onset. Along with DAA inefficacy, the more severity of depression is noted when the latter occurs in the premotor phase of PD and at the stage of MF.

Italian version of the Starkstein Apathy Scale (SAS-I) and a shortened version (SAS-6) to assess "pure apathy" symptoms: normative study on 392 individuals.

The present normative study aimed to (1) develop the Italian version of the Starkstein Apathy Scale (SAS-I) and (2) construct a shortened version including only the most sensitive items to "pure apathy" experiences. The normative sample included 392 healthy subjects. A regression-based procedure was used to explore the effects of sex, age, and education on the raw SAS-I score. A correction grid was designed for adjusting raw scores by adding or subtracting the contribution of any significant variable and net of sociodemographic interindividual differences. Cutoff scores were also calculated and fixed at the external tolerance limit on the ninety-fifth centile. To obtain the shortened version, each SAS-I item was correlated with the Beck's Depression Inventory (BDI) score. The only items showing no correlation with BDI were implemented to bypass the well-known overlap between apathetic and depressive symptoms. The mean raw SAS-I score was 11.27 (SD = 4.42). A significant education effect was observed, with highly educated subjects obtaining lower scores than lowly educated ones. The proposed general cutoff score was 20.68. The SAS-I had fair internal consistency and discriminant validity. Internal consistency increased by removing item 3. The new SAS-6 included items 1, 2, 4, 10, 11, and 13 of the original scale. The SAS-I is a reliable assessment tool to support the diagnosis of apathy. The SAS-6, instead, is a brief questionnaire useful for quickly screening apathetic symptoms in outpatient practice, addressing or not the clinician to further investigations.

Psychoemotional and cognitive characteristics in patients at the early stages of Parkinson’s disease

The purpose of the study was to assess psychoemotional and cognitive characteristics in patients at the early stages of Parkinson’s disease (PD) by neuropsychological and neurophysiological examinations. Materials and methods. A total of 40 PD patients with Hoehn and Yahr stage I–II (19 patients with stage I PD and 21 patients with stage II PD) were examined. A general physical examination and examination of the nervous system were performed in each group of patients. Neuropsychological characteristics were studied with the Unified Parkinson’s Disease Rating Scale (MDS UPDRS) , the Beck Depression Inventory , Starkstein Apathy Scale, Zung Anxiety Rating Scale, Vein Night Sleep Scale, Boston Stress Test. The cognitive functions were examined by the Montreal Cognitive Assessment (MoCA) scale and cognitive evoked potentials (CEP) P300. Results. A significant increase in PD symptoms (motor and non-motor) severity (P ˂ 0.001) according to MDS UPDRS data depending on PD stage was found. The anxiety level (P = 0.02) according to Zung Anxiety Rating Scale data and apathy level (P = 0.026) measured by Starkstein Apathy Scale, were significantly higher at stage II PD. Cognitive impairments were worsened according to the MoCA scale (P = 0.003) in 87.5 % of the patients. The prolongation of N2 latency in the right frontal area (P = 0.05) and P300 latency in all brain areas (P ˂ 0.01) were observed in stage II PD patients. Conclusions. There was a significant difference between PD symptoms severity (motor and non-motor) in stage I and II PD patients according to MDS UPDRS. Stage II PD patients were characterized by worse cognitive impairments, increased level of anxiety and apathy as compared to stage I PD patients. The difference between cognitive decline severity in patients with PD depending on the stage was confirmed by P300 latency prolongation in stage II PD patients.

Apathy in frontotemporal dementia is related to medial prefrontal atrophy and is independent of executive dysfunction

IntroductionApathy is the most common neuropsychiatric syndrome in behavioral variant frontotemporal dementia (bvFTD), and encompasses cognitive, behavioral and affective symptoms. The neural basis of apathy in bvFTD is not completely understood. Previous neuroimaging studies have poorly considered executive impairment and dementia severity as possible confounding factors. Herein we investigated the neural basis of apathy in bvFTD through structural neuroimaging taking into account these factors. MethodsWe included patients with probable bvFTD (n = 21) and cognitively healthy controls (HC, n = 22). Participants were matched for age, sex and schooling. All subjects underwent a thorough neuropsychological examination, including tests for executive functions and social cognition. Apathy was assessed with the Starkstein Apathy Scale (SAS). All subjects underwent 3T brain MRI. We investigated correlations between SAS scores and gray matter atrophy within the bvFTD group. Executive function (Frontal Assessment Battery) and disease severity were considered as covariates in neuroimaging analyses. ResultsCompared to HC, bvFTD patients had lower scores on global cognitive efficiency, executive functions and social cognition. All bvFTD had clinically relevant apathy (scores greater than 14 in the SAS). Performance in executive function tests did not correlate with apathy scores. The severity of apathy was negatively correlated with gray matter volumes in midline prefrontal regions, namely orbitofrontal cortex and both anterior and dorsal regions of cingulate cortex. ConclusionsApathy in bvFTD is related to a specific network of prefrontal cortical areas critically involved in effort-based behavior for rewards and appears to be independent of executive dysfunction.

Exercise increases caudate dopamine release and ventral striatal activation in Parkinson's disease.

The objective of this study was to examine the effects of aerobic exercise on evoked dopamine release and activity of the ventral striatum using positron emission tomography and functional magnetic resonance imaging in Parkinson's disease (PD). Thirty-five participants were randomly allocated to a 36-session aerobic exercise or control intervention. Each participant underwent an functional magnetic resonance imaging scan while playing a reward task before and after the intervention to determine the effect of exercise on the activity of the ventral striatum in anticipation of reward. A subset of participants (n = 25) completed [11 C] raclopride positron emission tomography scans to determine the effect of aerobic exercise on repetitive transcranial magnetic stimulation-evoked release of endogenous dopamine in the dorsal striatum. All participants completed motor (MDS-UPDRS part III, finger tapping, Timed-up-and-go) and nonmotor assessments (Starkstein Apathy Scale, Beck Depression Inventory, reaction time, Positive and Negative Affect Schedule, Trail Making Test [A and B], and Montreal Cognitive Assessment) before and after the interventions. The aerobic group exhibited increased activity in the ventral striatum during functional magnetic resonance imaging in anticipation of 75% probability of reward (P = 0.01). The aerobic group also demonstrated increased repetitive transcranial magnetic stimulation-evoked dopamine release in the caudate nucleus (P = 0.04) and increased baseline nondisplaceable binding potential in the posterior putamen of the less affected repetitive transcranial magnetic stimulation-stimulated hemisphere measured by position emission tomography (P = 0.03). Aerobic exercise alters the responsivity of the ventral striatum, likely related to changes to the mesolimbic dopaminergic pathway, and increases evoked dopamine release in the caudate nucleus. This suggests that the therapeutic benefits of exercise are in part related to corticostriatal plasticity and enhanced dopamine release. © 2019 International Parkinson and Movement Disorder Society.

Association of daily physical activity with cognition and mood disorders in treatment-naive patients with early-stage Parkinson's disease.

To determine the association of daily physical activity with cognition, mood disorders, and olfactory function in treatment-naive patients with early-stage Parkinson's disease (PD). The study subjects were 52 treatment-naive patients with early-stage PD (< 80years). Daily physical activity was measured using a wearable sensor with a built-in triaxial accelerometer, and its association with cognition [mini-mental state examination (MMSE), clock-drawing test (CDT), frontal assessment battery (FAB), and behavioral assessment of the dysexecutive syndrome (BADS)], depressive symptoms [Beck Depression Inventory-Second Edition (BDI-II)], apathy [Starkstein Apathy Scale (AS)], and olfactory function [Odor Stick Identification Test for the Japanese (OSIT-J)] was analyzed using multiple linear regression after adjustment for age, sex, and education status. The daily physical activity (0.42 ± 0.11m/s2) of the PD group was significantly lower than that of healthy controls (p < 0.001). Moreover, the daily physical activity of the PD group was significantly associated with FAB (β = 0.337, p = 0.027) and BADS (β = 0.374, p = 0.017) scores, but not with MMSE, CDT, BDI-II, AS, and OSIT-J scores. The daily physical activity is significantly reduced in treatment-naive patients with early-stage PD, and the low activity correlates with frontal/executive function.

Design and validation of a new instrument to assess fear of falling in Parkinson's disease

Fear of falling may be significantly associated with falls in Parkinson's disease (PD) and may have a negative impact on quality of life. Nevertheless, there are no valid and reliable tools to examine this condition in PD. The objective of this study was to design and determine the psychometric attributes of an instrument to assess fear of falling in PD. A prospective 1-year, 2-phase study was conducted to validate the Fear of Falling Scale, a self-assessed instrument for assessing fear of falling in PD. During phase 1, we designed a scale to measure the severity of fear of falling and determine its baseline psychometric characteristics, whereas phase 2 was a 1-year follow-up study to assess the frequency of falls and other clinical factors linked to fear of falling. Convergent and discriminant validity were assessed against the Fear of Falling Measure and the Starkstein Apathy Scale, respectively. The Fear of Falling Scale showed high internal consistency, test-retest reliability, and strong convergent and discriminant validity. There was a significant association between fear of falling score and the presence of both generalized anxiety disorder and major depression, poor balance-related motor ability, increased nonmotor symptoms of PD, more severe impairments in activities of daily living, and increased motor fluctuations. Finally, generalized anxiety disorder was a significant predictor of number of falls during a 12-month follow-up period. The Fear of Falling Scale is a valid and reliable instrument to assess fear of falling in PD. Fear of falling in PD is associated with specific psychiatric and motor disorders and is significantly related to the performance of balance-related motor functions. © 2019 International Parkinson and Movement Disorder Society.

Fatigue in patients with vestibular schwannoma.

Patients with vestibular schwannoma (VS) often complain about tiredness, exhaustion, lack of energy, and strength, but such symptoms of fatigue have scarcely been objectified and analyzed in a VS population. We aimed to characterize fatigue in a cohort of patients with VS and compare such symptoms with a control group. All patients who attended an educational course for patients with VS were surveyed with validated tools for assessment of fatigue (fatigue severity scale), anxiety and depression (hospital anxiety and depression scale), sleepiness (Epworth sleepiness scale), and apathy (Starkstein apathy scale). Quality of Life was assessed with the disease-specific Penn Acoustic Neuroma Quality of Life (PANQOL). Symptom severity was estimated with a visual analog scale (VAS). The results have been compared to a control group consisting of patient companions. Data from 88 VS patients and 49 controls were analyzed. The controls had similar age and sex distribution as patients. Fifty-seven percent of VS patients had significant fatigue, compared to 25% in the control group. The mean fatigue score was 4.1 for the patients, and 2.8 for controls. Patients with fatigue were more likely to have depression, anxiety, sleepiness, and apathy. No correlation of fatigue was found with age, gender, or treatment modality. Regression analyses revealed depression, apathy, and vertigo to be predictors of fatigue. Fatigue was strongly correlated to QoL. Almost six out of ten VS patients had fatigue, significantly higher than the control group. Interest and focus on fatigue in VS patients can improve the patient's QoL.

Emotional Processing Impairments in Apathetic Patients with Parkinson's Disease: An ERP Study in Early Time Windows.

We investigated emotional processing in apathetic patients with Parkinson's disease (PD) by observing components of event-related potentials (ERPs) in early time windows. Forty PD patients and 21 healthy controls (HCs) were enrolled. The Starkstein Apathy Scale (SAS) was used to divide the PD patients into apathetic and nonapathetic groups. Cognitive function was evaluated by the forward and backward Digit Span tests, Trail Making Test (TMT), and Word Fluency Test. The participants were required to recognize positive, neutral, and negative emotional faces and engage in an emotion categorization task while EEG was recorded. The time to completion for the TMT (Part A and Part B) from highest to lowest was in the order of apathetic group > nonapathetic group > HC group. Compared with the nonapathetic and HC groups, in the apathetic group, P100 amplitudes were smaller for positive expressions in the right hemisphere and latencies were longer for positive expressions in the left hemisphere, while latencies were longer for neutral expressions bilaterally. Compared with the nonapathetic group, in the apathetic group, N170 amplitudes were attenuated and latencies were delayed for neutral and negative expressions in the right hemisphere. A trend towards larger N170 amplitudes in the right hemisphere than in the left was observed in the nonapathetic and HC groups, but this difference was not significant in the apathetic group. In the apathetic group, bilateral P100 amplitudes elicited by negative expressions were negatively correlated with SAS scores, and SAS scores were positively correlated with Part B of the TMT. N170 amplitudes elicited by negative expressions in the right hemisphere were negatively correlated with SAS in the apathetic group and with Part B of TMT in both PD groups. Our findings suggested that emotional processing was impaired in apathetic PD patients and that the right hemisphere was more sensitive to reflecting this impairment in the early time windows of ERPs.

Ventral tegmental area deep brain stimulation for chronic cluster headache: Effects on cognition, mood, pain report behaviour and quality of life.

Deep brain stimulation in the ventral tegmental area (VTA-DBS) has provided remarkable therapeutic benefits in decreasing headache frequency and severity in patients with medically refractory chronic cluster headache (CH). However, to date the effects of VTA-DBS on cognition, mood and quality of life have not been examined in detail. The aim of the present study was to do so in a case series of 18 consecutive patients with cluster headache who underwent implantation of deep brain stimulation electrodes in the ventral tegmental area. The patients were evaluated preoperatively and after a mean of 14 months of VTA-DBS on tests of global cognition (Mini Mental State Examination), intelligence (Wechsler Abbreviated Scale of Intelligence), verbal memory (California Verbal Learning Test-II), executive function (Delis-Kaplan Executive Function System), and attention (Paced Auditory Serial Addition Test). Depression (Beck Depression Inventory and Hospital Anxiety and Depression Rating Scale-D), anxiety (Hospital Anxiety and Depression Rating Scale-A), apathy (Starkstein Apathy Scale), and hopelessness (Beck Hopelessness Scale) were also assessed. Subjective pain experience (McGill Pain Questionnaire), behaviour (Pain Behaviour Checklist) and quality of life (Short Form-36) were also evaluated at the same time points. VTA-DBS resulted in significant improvement of headache frequency (from a mean of five to two attacks daily, p < .001) and severity (from mean Verbal Rating Scale [VRS] of 10 to 7, p < .001) which was associated with significant reduction of anxiety (from mean HADS-A of 11.94 to 8.00, p < .001) and help-seeking behaviours (from mean PBC of 4.00 to 2.61, p < .001). VTA-DBS did not produce any significant change to any tests of cognitive function and any other outcome measures (BDI, HADS-D, SAS, BHS, McGill Pain Questionnaire, Short Form-36). We confirm the efficacy of VTA-DBS in the treatment of medically refractory chronic cluster headache. The reduction of headache frequency and severity was associated with a significant reduction of anxiety. Furthermore, the result suggests that VTA-DBS for chronic cluster headache improves pain-related help-seeking behaviours and does not produce any change in cognition.

Abstract WP204: Low-grade Inflammation is Associated With Apathy Indirectly Through Deep White Matter Lesions in Community-dwelling Older Adults

Background: Low-grade inflammation is implicated in the pathogenesis of small vessel disease of the brain. Furthermore, systemic inflammation has been associated with apathy. Because our previous study showed the association between deep white matter lesions (DWMLs) and apathy, we investigated the association between inflammation, DWMLs, and apathy. Methods: We analyzed the brain magnetic resonance imaging (MRI) findings in 259 community-dwelling adults (122 men and 137 women) with a mean age of 64.8 years. Serum concentrations of high-sensitivity C-reactive protein (CRP) were measured by a quantitative enzyme-linked immunosorbent assay with a sensitivity of 22 ng/L. Each item of the Starkstein apathy scale was quantified on a visual analogue scale. The association between silent brain lesions and CRP was tested using the forward stepwise method of logistic regression analysis. We used structural equation modeling (SEM) to test the contribution of inflammation and silent brain lesions to the apathetic behavior. Results: Although CRP level distribution was highly skewed (median: 0.589 mg/L, interquartile range: 0.292-1.326 mg/L), log-transformed CRP values (log10 CRP) were normally distributed. Medium to high tertiles of CRP were associated with metabolic syndrome. Logistic regression analysis revealed that log10 CRP (odds ratio [OR]: 2.90; 95% confidence interval [95%CI]: 1.25-6.71) was independently associated with confluent but not total DWMLs. Metabolic syndrome and age were also associated with confluent DWMLs. Path analysis based on SEM indicated that the direct path from log10 CRP to DWMLs was significant (β = 0.12, P = 0.039). The direct paths from metabolic syndrome to log10 CRP and to DWMLs were also significant. The direct path from DWMLs to apathy was significant (β = –0.17, P = 0.007) as was the direct path from education to apathy (β = 0.18, P = 0.003). However, the direct path from log10 CRP to apathy was not significant. The measures of model fitness showed that the presented model reasonably fit the data. Conclusions: Independent of common vascular risk factors, elevated serum CRP levels were associated with confluent DWMLs. Although DWMLs were associated with apathy, direct association between inflammation and apathy was not shown.

Sardinian Folk Dance for Individuals with Parkinson's Disease: A Randomized Controlled Pilot Trial.

Among different exercise models proposed for individuals with Parkinson's disease (IwPD), the popularity of traditional forms of dance is increasing. The aim of this study was to evaluate the effects of Sardinian folk dance (Ballu Sardu, BS) on functional performance and motor and nonmotor symptoms in IwPD. Single-blind, randomized controlled pilot trial. Outpatient health clinic. Twenty IwPD (13M, 7F; 67.4 ± 6.1 years) were randomly assigned to BS (n = 10) or usual care (n = 10). The dance program consisted of two sessions/week, 90-min/class, for 12 weeks. Motor and nonmotor symptoms, as well as functional performance, were evaluated using different questionnaires and tests such as the Unified Parkinson's Disease Rating Scale Part-III (UPDRS-III), 6-min walking test (6MWT), Berg Balance Scale (BBS), Timed Up-and-Go (TUG) test, Five Times Sit-to-Stand Test (FTSST), Back Scratch Test (BST), Sit-and-Reach Test (SRT), instrumented gait analysis, Parkinson's Disease Fatigue Scale (PFS-16), Beck Depression Inventory, Starkstein Apathy Scale (SAS), and Montreal Cognitive Assessment (MOCA) scale. Repeated-measures analysis of variance revealed significant Time × Group interactions for UPDRS-III and functional variables such as the 6MWT, BBS, FTSST, TUG (all, p < 0.001), BST (p = 0.04), and gait analysis parameters (stride length, p = 0.031; gait speed, p = 0.049; and gait fatigue index (GFI), p = 0.005). For nonmotor symptoms, significant Time × Group interactions for depression (p < 0.001), apathy (p = 0.016), and MOCA scores (p = 0.012) were observed. Of note, for GFI and SAS, the BS group only showed a trend toward improvement, while the condition of the controls worsened significantly. No between-group differences were observed for SRT and PFS-16. BS is an enjoyable activity, which has been proved to be superior to usual care alone in inducing changes in different motor and nonmotor symptoms associated with PD. Results show that BS can be considered a safe tool for contrasting impairments observed in IwPD due to the intrinsic nature of the neurodegenerative disease.

Characteristics of apathy in treatment-naïve patients with Parkinson’s disease

Introduction: Although apathy is a common psychiatric symptom of Parkinson’s disease (PD), there are many unknown aspects of its pathology. This study aimed to investigate the characteristics of apathy in treatment-naïve patients with early-stage PD. Methods: Fifty treatment-naïve patients with early-stage PD were divided into 1 of 2 groups—apathetic or non-apathetic—based on Starkstein Apathy Scale (AS) scores. Cognitive function, depressive symptoms, olfactory function, and motor severity were compared between the two groups using validated assessment scales. Multiple linear regression was performed to assess the association between AS scores and clinical parameters. Results: Apathy (AS score ≥16) was observed in 13 (26%) patients. Assessment scale scores (Beck Depression Inventory-Second Edition [p < .004]; modified Hoehn & Yahr stage [p = .039]; Unified Parkinson’s Disease Rating Scale part III [p < .001]) were significantly higher in apathetic patients than in non-apathetic patients. Significant association between these scale scores and AS score was also evident (all p ≤ .001). There were no significant differences in the test scores derived from several other validated scales. Conclusion: Apathy was observed in 26% of treatment-naïve patients with early-stage PD. Significant association between apathy and motor severity was found, suggesting that dysfunction of the dopaminergic pathway is involved in the pathology of apathy.

Habitual exercisers versus sedentary subjects with Parkinson's Disease: Multimodal PET and fMRI study.

The benefits of exercise in PD have been linked to enhanced dopamine (DA) transmission in the striatum. To examine differences in DA release, reward signaling, and clinical features between habitual exercisers and sedentary subjects with PD. Eight habitual exercisers and 9 sedentary subjects completed [11 C]raclopride PET scans before and after stationary cycling to determine exercise-induced release of endogenous DA in the dorsal striatum. Additionally, functional MRI assessed ventral striatum activation during reward anticipation. All participants completed motor (UPDRS III; finger tapping; and timed-up-and-go) and nonmotor (Beck Depression Inventory; Starkstein Apathy Scale) assessments. [11 C]Raclopride analysis before and after stationary cycling demonstrated greater DA release in the caudate nuclei of habitual exercisers compared to sedentary subjects (P < 0.05). Habitual exercisers revealed greater activation of ventral striatum during the functional MRI reward task (P < 0.05) and lower apathy (P < 0.05) and bradykinesia (P < 0.05) scores versus sedentary subjects. Habitual exercise is associated with preservation of motor and nonmotor function, possibly mediated by increased DA release. This study formulates a foundation for prospective, randomized controlled studies. © 2018 International Parkinson and Movement Disorder Society.

Psychometric properties of apathy scales in Parkinson's disease: a systematic review.

Apathy is among the most prevalent neuropsychiatric symptom experienced in Parkinson's disease (PD) and can be assessed with a variety of scales. To identify which scale is most suitable for apathy assessment in PD, the psychometric properties of each scale and its sensitivity to change were analyzed. The methodological quality of the studies ranged from adequate to excellent. The Lille Apathy Rating Scale demonstrated consistently favorable psychometric properties and was used in two of four clinical trials found. The Starkstein Apathy Scale was the only other scale used in clinical trials. Further work is necessary to develop a gold standard for assessing apathy in PD.

P68. A double-blind, sham-controlled phase-1b study of combined STN and NBM-DBS in PD and mild to moderate Parkinson’s dementia (DEMPARK-DBS)

Introduction Subthalamic nucleus (STN)-DBS has proven to be a safe and long-term effective treatment for advanced Parkinson’s disease (PD). One of the contraindications for DBS is marginal or definite cognitive decline, which excludes a relevant amount of PD patients otherwise eligible for this effective therapy. There is growing evidence from case or series studies of DBS in cholinergic brain structures to stabilize or improve cognitive function in dementia. We aim to provide proof of safety of combined STN and Nucleus Basalis Meynert (NBM) stimulation in treating advanced PD having mild to moderate dementia. Design/Method In a prospective, monocentric study with double-blinded, randomized delayed-activation of NMB-stimulation 12 patients with idiopathic PD (Hoehn and Yahr stage ⩾2 in medication off, aged 45–75, disease duration ⩾5 years, improve of PD symptoms by ⩾30% in a levodopa challenge) can be included when the following criteria are met: medical refractory motor fluctuations or tremor with eligibility for bilateral STN-DBS but presence of mild to moderate Parkinson’s disease dementia (PDD) as defined by the MDS consensus guidelines (Mini–Mental State Examination score: 10–24). Eligible patients will be implanted with a rechargeable DBS System (Boston Scientific Vercise TM) with electrodes placed bilaterally in each STN and NBM. All 4 electrodes will be connected via a splitter to a single pacemaker. To analyze sole effects of DBS surgery on motor state and cognition, STN-DBS will be activated after 4 ± 1 weeks in all subjects. After 12 weeks of active STN-DBS a further motor-functional and cognitive assessment will be performed before randomization to either 24-weeks of sham- or instant active NBM-DBS. Subjects randomized to NBM-sham will have a delayed activation of NBM-DBS after the 24-weeks-sham-period. Subsequent assessment will be performed for all subjects after 24 and 48 weeks of active NBM stimulation. Outcome parameters and assessments SAE and safety parameters; UPDRS, Clinical Dyskinesia Rating Scale; ADCS-CGIC & -ADL, Zarit-Burden Interview, SF-36; BDI-II, Starkstein Apathy Scale, PDQ-39, EQ-5D; Neuropsychiatric Inventory, ADAS-Cog, Verbal Fluency (RWT), Wisconsin Card Sorting test, Trail Making test, Stroop test (Victoria vs.), Symbol Digit Modalities test, Brief Test of Attention. Current state Up to now 4 patients could be enrolled and were already implanted. First results of STN-stimulation will be presented at the congress. Conclusion Our study will determine safety of additional NBM stimulation in PD patients with PDD and may give first insight if it can slow or improve cognitive decline. We therefore hope to encourage other centers to refer eligible patients.

Diagnosing and Treating Apathy in Dementia

Diagnosing and Treating Apathy in Dementia

Correlation among olfactory function, motors' symptoms, cognitive impairment, apathy, and fatigue in patients with Parkinson's disease.

Although Parkinson's disease (PD) is usually considered as a movement disorder, it is strongly associated with non-motor symptoms (NMS), including smell and taste dysfunctions, cognitive impairment, apathy, fatigue, and autonomic dysregulation. Olfactory deficit is considered the most common NMS in PD preceding the motor symptoms for years. The aim of this study was to investigate olfactory function, cognitive impairment, apathy, and fatigue in patients with PD in comparison with healthy controls, and subsequently to analyse the correlations between these NMS and motor symptoms severity in subjects with PD. One hundred and forty-seven participants were enrolled (96 PD patients, mean age in years 67.5, SD 7.2; 51 healthy controls; mean age 65.1, SD 11.8). Olfactory function was evaluated using the Sniffin' Sticks test (odor detection threshold, discrimination and identification). The Montreal Cognitive Assessment (MoCA) was used to assess cognitive impairment. Apathy was examined by the self-report version of Starkstein Apathy Scale and fatigue was evaluated with the Parkinson's Disease Fatigue Scale. PD patients showed severe impairment in odor detection threshold, discrimination, and identification compared to healthy controls. Moreover, in PD patients, apathy and fatigue scores were significantly increased, while MoCA scores were decreased in comparison with controls. Multivariate linear regression analyses showed that both apathy and Unified PD Rating Scale (UPDRS) were associated with odor identification, discrimination and Threshold-Discrimination-Identification (TDI) score. In conclusion, our results reported changes in apathy and motor disability as significant predictors in alterations of odor identification, discrimination and TDI score. Furthermore, these data suggest that olfactory dysfunction might progress in tight relation with motor impairment UPDRS but also with non-motor symptoms such as apathy.

Behavioural outcomes of subthalamic stimulation and medical therapy versus medical therapy alone for Parkinson's disease with early motor complications (EARLYSTIM trial): secondary analysis of an open-label randomised trial

Although subthalamic stimulation is a recognised treatment for motor complications in Parkinson's disease, reports on behavioural outcomes are controversial, which represents a major challenge when counselling candidates for subthalamic stimulation. We aimed to assess changes in behaviour in patients with Parkinson's disease receiving combined treatment with subthalamic stimulation and medical therapy over a 2-year follow-up period as compared with the behavioural evolution under medical therapy alone. We did a parallel, open-label study (EARLYSTIM) at 17 surgical centres in France (n=8) and Germany (n=9). We recruited patients with Parkinson's disease who were disabled by early motor complications. Participants were randomly allocated (1:1) to either medical therapy alone or bilateral subthalamic stimulation plus medical therapy. The primary outcome was mean change in quality of life from baseline to 2 years. A secondary analysis was also done to assess behavioural outcomes. We used the Ardouin Scale of Behavior in Parkinson's Disease to assess changes in behaviour between baseline and 2-year follow-up. Apathy was also measured using the Starkstein Apathy Scale, and depression was assessed with the Beck Depression Inventory. The secondary analysis was done in all patients recruited. We used a generalised estimating equations (GEE) regression model for individual items and mixed model regression for subscores of the Ardouin scale and the apathy and depression scales. This trial is registered with ClinicalTrials.gov, number NCT00354133. The primary analysis has been reported elsewhere; this report presents the secondary analysis only. Between July, 2006, and November, 2009, 251 participants were recruited, of whom 127 were allocated medical therapy alone and 124 were assigned bilateral subthalamic stimulation plus medical therapy. At 2-year follow-up, the levodopa-equivalent dose was reduced by 39% (-363·3 mg/day [SE 41·8]) in individuals allocated bilateral subthalamic stimulation plus medical therapy and was increased by 21% (245·8 mg/day [40·4]) in those assigned medical therapy alone (p<0·0001). Neuropsychiatric fluctuations decreased with bilateral subthalamic stimulation plus medical therapy during 2-year follow-up (mean change -0·65 points [SE 0·15]) and did not change with medical therapy alone (-0·02 points [0·15]); the between-group difference in change from baseline was significant (p=0·0028). At 2 years, the Ardouin scale subscore for hyperdopaminergic behavioural disorders had decreased with bilateral subthalamic stimulation plus medical therapy (mean change -1·26 points [SE 0·35]) and had increased with medical therapy alone (1·12 points [0·35]); the between-group difference was significant (p<0·0001). Mean change from baseline at 2 years in the Ardouin scale subscore for hypodopaminergic behavioural disorders, the Starkstein Apathy Scale score, and the Beck Depression Inventory score did not differ between treatment groups. Antidepressants were stopped in 12 patients assigned bilateral subthalamic stimulation plus medical therapy versus four patients allocated medical therapy alone. Neuroleptics were started in nine patients assigned medical therapy alone versus one patient allocated bilateral subthalamic stimulation plus medical therapy. During the 2-year follow-up, two individuals assigned bilateral subthalamic stimulation plus medical therapy and one patient allocated medical therapy alone died by suicide. In a large cohort with Parkinson's disease and early motor complications, better overall behavioural outcomes were noted with bilateral subthalamic stimulation plus medical therapy compared with medical therapy alone. The presence of hyperdopaminergic behaviours and neuropsychiatric fluctuations can be judged additional arguments in favour of subthalamic stimulation if surgery is considered for disabling motor complications. German Federal Ministry of Education and Research, French Programme Hospitalier de Recherche Clinique National, and Medtronic.