Consecutive Parkinson's Disease Research Articles

Neurosteroid Levels in GBA Mutated and Non-Mutated Parkinson's Disease: A Possible Factor Influencing Clinical Phenotype?

Neurosteroids are pleiotropic molecules involved in various neurodegenerative diseases with neuroinflammation. We assessed neurosteroids' serum levels in a cohort of Parkinson's Disease (PD) patients with heterozygous glucocerebrosidase (GBA) mutations (GBA-PD) compared with matched cohorts of consecutive non-mutated PD (NM-PD) patients and healthy subjects with (GBA-HC) and without (NM-HC) GBA mutations. A consecutive cohort of GBA-PD was paired for age, sex, disease duration, Hoehn and Yahr stage, and comorbidities with a cohort of consecutive NM-PD. Two cohorts of GBA-HC and HC were also considered. Clinical assessment included the Movement Disorder Society revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and the Montreal Cognitive Assessment (MoCA). Serum samples were processed and analyzed by liquid chromatography coupled with the triple quadrupole mass spectrometry. Twenty-two GBA-PD (males: 11, age: 63.68), 22 NM-PD (males: 11, age: 63.05), 14 GBA-HC (males: 8; age: 49.36), and 15 HC (males: 4; age: 60.60) were studied. Compared to NM-PD, GBA-PD showed more hallucinations and psychosis (p < 0.05, Fisher's exact test) and higher MDS-UPDRS part-II (p < 0.05). Most of the serum neurosteroids were reduced in both GBA-PD and NM-PD compared to the respective control cohorts, except for 5α-dihydroprogesterone. Allopregnanolone was the only neurosteroid significantly lower (p < 0.01, Dunn's test) in NM-PD compared to GBA-PD patients. Only in GBA-PD, allopregnanolone, and pregnanolone levels correlated (Spearman) with a more severe MDS-UPDRS part-III. Allopregnanolone levels also negatively correlated with MoCA scores, and pregnanolone levels correlated with more pronounced bradykinesia. This pilot study provides the first observation of changes in neurosteroid peripheral levels in GBA-PD. The involvement of the observed changes in the development of neuropsychological and motor symptoms of GBA-PD deserves further attention.

Delayed-onset seizures after subthalamic nucleus deep brain stimulation surgery for Parkinson’s disease

BackgroundDelayed-onset seizures after deep brain stimulation (DBS) surgery were seldom reported. This study summarized the clinical characteristics of delayed-onset seizures after subthalamic nucleus (STN) DBS surgery for Parkinson’s disease (PD) and analyzed risk factors. MethodsA single-center retrospective study containing consecutive STN-DBS PD patients from 2006 to 2021 was performed. Seizures occurred during the DBS surgery or within one month after DBS surgery were identified based on routine clinical records. Patients with postoperative magnetic resonance imaging (MRI) were included to further analyze the risk factors for postoperative seizures with univariate and multivariate statistical methods. Results341 consecutive PD patients treated with bilateral STN-DBS surgery wereidentified, and five patients experienced seizures after DBS surgery with an incidence of 1.47 %. All seizures of the five cases were characterized as delayed onset with average 12 days post-operatively. All seizures presented as generalized tonic-clonic seizures and didn’t recur after the first onset. In those seizures cases, peri-electrode edema was found in both hemispheres without hemorrhage and infarction. The average diameter of peri-electrode edema of patients with seizures was larger than those without seizures (3.15 ± 1.00 cm vs 1.57 ± 1.02 cm, p = 0.005). Multivariate risk factor analysis indicated that seizures were only associated with the diameter of peri-electrode edema (OR 4.144, 95 % CI 1.269–13.530, p = 0.019). ConclusionsDelayed-onset seizures after STN-DBS surgery in PD patients were uncommon with an incidence of 1.47 % in this study. The seizures were transient and self-limiting, with no developing into chronic epilepsy. Peri-electrode edema was a risk factor for delayed-onset seizures after DBS surgery. Patients with an average peri-electrode edema diameter > 2.70 cm had a higher risk to develop seizures.

DRD3 Predicts Cognitive Impairment and Anxiety in Parkinson's Disease: Susceptibility and Protective Effects.

A possible genetic contribution of dopamine D3 receptor (DRD3) to cognitive impairment in Parkinson's disease (PD) has yet to be investigated. To explore the effects of rs6280 (Ser9Gly) genotype on PD patients' cognitive performance and to clarify possible interactions with psychopathology. Two hundred and fifty-three consecutive PD patients underwent neurological and neuropsychological evaluations, which included: Unified Parkinson's Disease Rating Scale (UPDRS), Hoehn & Yahr scale (H&Y), Dementia Rating Scale-2 (DRS-2), and Hospital Anxiety and Depression Scale (HADS). rs6280 polymorphism was genotyped for all PD patients and for 270 ethnically matched healthy volunteers (HC). Non-parametric group comparisons and logistic regressions were used for data analyses. rs6280 genotype did not differ between PD and HC groups. PD patients with rs6280 CC genotype had more impaired cognitive performance (i.e., <1st percentile of demographically adjusted norms) on DRS-2 subscales Initiation/Perseveration and Construction than those with TT genotype. These associations remained statistically significant when other covariates (e.g., demographic features, disease duration, severity of motor symptoms in OFF and ON states, anti-parkinsonian medication, and psychopathology symptoms) were taken into consideration. PD patients with rs6280 TC had less anxiety (i.e., HADS Anxiety≥11) than those with TT (p = 0.012). This association was also independent of other covariates. Study findings suggest that rs6280 CC genotype predisposes to executive dysfunction and visuoconstructional deficits, whereas the heterozygous genotype protects from anxiety in PD. These effects do not appear to be dependent of one another. rs6280 is not a genotypic susceptibility factor for PD.

Blood D-serine levels correlate with aging and dopaminergic treatment in Parkinson's disease

We recently described increased D- and L-serine concentrations in the striatum of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys, the post-mortem caudate-putamen of human Parkinson's disease (PD) brains and the cerebrospinal fluid (CSF) of de novo living PD patients. However, data regarding blood D- and L-serine levels in PD are scarce. Here, we investigated whether the serum profile of D- and L-serine, as well as the other glutamate N-methyl-D-aspartate ionotropic receptor (NMDAR)-related amino acids, (i) differs between PD patients and healthy controls (HC) and (ii) correlates with clinical-demographic features and levodopa equivalent daily dose (LEDD) in PD. Eighty-three consecutive PD patients and forty-one HC were enrolled. PD cohort underwent an extensive clinical characterization. Serum levels of D- and L-serine, L-glutamate, L-glutamine, L-aspartate, L-asparagine and glycine were determined using High Performance Liquid Chromatography.In age- and sex-adjusted analyses, no differences emerged in the serum levels of D-serine, L-serine and other NMDAR-related amino acids between PD and HC. However, we found that D-serine and D−/Total serine ratio positively correlated with age in PD but not in HC, and also with PD age at onset. Moreover, we found that higher LEDD correlated with lower levels of D-serine and the other excitatory amino acids. Following these results, the addition of LEDD as covariate in the analyses disclosed a selective significant increase of D-serine in PD compared to HC (Δ ≈ 38%). Overall, these findings suggest that serum D-serine and D−/Total serine may represent a valuable biochemical signature of PD.

Factor analysis for construct validity of a trunk impairment scale in Parkinson's disease: a cross-sectional study.

To investigate the construct validity of the Trunk Impairment Scale (TIS), which was developed to assess trunk impairment in patients with stroke, in patients with Parkinson's disease (PD). This retrospective, cross-sectional study enrolled consecutive PD inpatients. Correlation analysis was performed to clarify whether the TIS assessment was related to other balance functions, lower extremity muscle strength, or walking ability. Factor analysis was performed to see how the background factors of TIS differ from balance function, lower limb muscle strength, and walking ability. Examining the data of 471 patients with PD, there were relationships between TIS and the Mini-Balance Evaluation Systems Test (r = 0.67), Barthel Index (r = 0.57), general lower limb extension torque (r = 0.51), two-minute walk test (r = 0.54), Hoehn and Yahr stage (r = -0.61), and Movement Disorder Society Unified Parkinson's Disease Rating Scale part III total points (r = -0.59). Factor analysis showed that TIS items were divided into three factors (an abdominal muscles and righting reflex component; a perception and verticality component; and a rotational component), differing from other scales that included clinical assessment items. The TIS can be useful for assessing the underlying trunk impairment as a basis for activities of daily living, gait function, and balance ability in patients with PD.

Early Detection of Depression in Parkinson's Disease: Psychometrics and Diagnostics of the Spanish Version of the Beck Depression Inventory.

Depression is one of the most disabling non-motor symptoms in Parkinson's disease (PD) and requires proper diagnosis as it negatively impacts patients' and their relatives quality of life. The present study aimed to examine the psychometric and diagnostic properties of the Beck Depression Inventory-I (BDI-I) in a Spanish PD cohort. Consecutive PD outpatients completed the Spanish version of the BDI-I and other questionnaires assessing anxiety and apathy. Patients' caregivers completed the depression/dysphoria domain of the Neuropsychiatric Inventory (NPI-D). The internal consistency, convergent and divergent validity and the factorial structure of BDI-I were evaluated, and an optimal cut-off was defined by means of the Youden index. The BDI-I proved to have a good internal consistency and was underpinned by a mono-component structure. Regarding construct validity, the BDI-I was substantially related to anxiety and apathy measures in PD. Furthermore, the BDI-I overall showed good accuracy with adequate sensitivity and specificity. The optimal cut-off point was defined at 10. We provided evidence of the psychometric and diagnostic properties of the Spanish version of the BDI-I as a screening tool for depression in Spanish speaking PD patients, suggesting its usefulness in clinical research and practice.

Fluctuations in Parkinson's disease and personalized medicine: bridging the gap with the neuropsychiatric fluctuation scale.

Neuropsychiatric fluctuations (NpsyF) are frequent and disabling in people with Parkinson's disease (PD). In OFF-medication, NpsyF entail minus neuropsychiatric symptoms (NPS) like anxiety, apathy, sadness, and fatigue. In ON-medication, NpsyF consist in plus NPS, such as high mood, hypomania, and hyperactivity. Accurate identification of these NpsyF is essential to optimize the overall PD management. Due to lack of punctual scales, the neuropsychiatric fluctuation scale (NFS) has been recently designed to assess NpsyF in real time. The NFS comprises 20 items with two subscores for plus and minus NPS, and a total score. To evaluate the psychometric properties of the NFS in PD. PD patients with motor fluctuations and healthy controls (HC) were assessed. In PD patients, the NFS was administrated in both the ON-and OFF-medication conditions, together with the movement disorders society-unified Parkinson disease rating scale parts I-IV. Depression (Beck depression scale II), apathy (Starkstein apathy scale) and non-motor fluctuations items of the Ardouin scale of behaviour in PD (ASBPD OFF and ON items) were also assessed. NFS internal structure was evaluated with principal component analysis consistency (PCA) in both medication conditions in PD patients and before emotional induction in HC. NFS internal consistency was assessed using Cronbach's alpha coefficient. NFS convergent and divergent validity was measured through correlations with BDI-II, Starktein, and ASBPD OFF and ON non motor items. Specificity was assessed comparing NFS global score between the HC and PD populations. Sensitivity was evaluated with t-student test comparing the ON-and the OFF-medication conditions for NFS global score and for minus and plus subscores. In total, 101 consecutive PD patients and 181 HC were included. In PD patients and HC, PCA highlighted one component that explained 32-35 and 42% of the variance, respectively. Internal consistency was good for both the NFS-plus (alpha =0.88) and NFS-minus items (alpha =0.8). The NFS showed a good specifity for PD (p < 0.0001) and a good sensitivity to the medication condition (p < 0.0001). The satisfactory properties of the NFS support its use to assess acute neuropsychiatric fluctuations in PD patients, adding to available tools.

IgG index of cerebrospinal fluid can reflect pathophysiology associated with Lewy bodies in Parkinson's disease

BackgroundNeuroinflammation is one of the pathophysiologies of Parkinson's disease (PD). Lewy bodies, the pathological hallmark of PD, emerge as a consequence of α-synuclein aggregation, and neuroinflammation is induced concurrently with this aggregation. Imaging and cerebrospinal fluid (CSF) biomarkers that reflect PD pathophysiology have been developed or are under investigation. The IgG index of CSF is a marker of inflammation, and may also reflect the pathophysiology of PD. AimWe examined if the IgG index reflects the pathophysiology of PD in drug-naïve PD patients. MethodThe subjects were 20 consecutive PD patients who underwent 123I-MIBG scintigraphy for assessment of the heart to mediastinum (H/M) ratio and wash out rate, 123I-Ioflupane SPECT for examination of the specific binding ratio in the striatum, and lumbar puncture before treatment. The CSF IgG index and levels of pathogenic proteins (total α-synuclein, oligomeric α-synuclein, total tau, phosphorylated tau and amyloid Aβ1–42) were determined. The IgG index was compared with the other parameters using Spearman correlation analysis. ResultsThe IgG index showed a significant correlation with the H/M ratio in early (r = −0.563, p = 0.010) and delayed (r = −0.466, p = 0.038) images in 123I-MIBG scintigraphy and with the CSF total tau level (r = −0.513, p = 0.021). ConclusionNeuroinflammation is involved in PD pathophysiology in some patients, and a higher IgG index indicates the presence of neuroinflammation accompanied by emergence of Lewy bodies.

The impact of deep brain stimulation of the subthalamic nucleus on facial emotion recognition in patients with Parkinson's disease.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is successful in patients with advanced Parkinson's disease (PD) but may worsen cognitive outcome, including facial emotion recognition (FER). Data-analyses on 59 consecutive PD patients with complete pre- and postoperative assessments, using a sensitive FER test, showed no changes in FER 1 year after STN-DBS surgery, both after group and individual analyses. These findings do however not exclude the impact of FER in and on itself on the outcome after STN-DBS.

Interplay between speech and gait variables in PD patients treated with STN-DBS: a long-term instrumental assessment.

To evaluate correlations between speech and gait parameters in the long-term and under different medication and subthalamic nucleus deep brain stimulation (STN-DBS) conditions in a cohort of advanced Parkinson's Disease (PD) patients. This observational study included consecutive PD patients treated with bilateral STN-DBS. Axial symptoms were evaluated using a standardized clinical-instrumental approach. Speech and gait were assessed by perceptual and acoustic analyses and by the instrumented timed up and go test (iTUG) respectively. Disease motor severity was evaluated with the total score and subscores of the UPDRS part III. Different stimulation and drug treatment conditions were assessed: on-stimulation/off-medication, off-stimulation/off-medication, and on-stimulation/on-medication. Twenty-five PD patients with a five-year median follow-up after surgery (range 3-7) were included (18 M; disease duration at surgery:10.44 [sd:4.62] years; age at surgery:58.40 [sd:5.73] years). In the off-stimulation/off-medication and on-stimulation/on-medication conditions, patients who spoke louder had also the greater acceleration of the trunk during gait whereas, in the on-stimulation/on-medication condition only, patients with the poorer voice quality were also the worse to perform sit to stand and gait phases of the iTUG. On the contrary, patients with the higher speech rate performed well the turning and walking phases of the iTUG. This study underlines the presence of different correlations between treatment effects of speech and gait parameters in PD patients treated with bilateral STN-DBS. This may allow us to better understand the common pathophysiological basis of these alterations and to develop a more specific and tailored rehabilitation approach for axial signs after surgery.

Pain experience in Parkinson's disease patients: preliminary results of a cohort study

Background: Pain is frequent in Parkinson’s disease (PD) and has a great impact on life quality. The aim of the study was to establish the presence of the pain in a cohort of PD patients. Material and methods: Study sample consisted of 102 consecutive PD patients, (mean age 61.51 ± 8.87 y.o.; disease duration 65.78 ± 41.34 mo.; 55 women and 47 men) evaluated for pain presence and divided into groups with and without pain: “PD pain +” and “PD pain -“ Results: The groups were similar according to ages (61.02 ± 9.61 vs. 62.51 ± 7.69 y.o.) and levodopa dose (729.85 ± 483.29 vs. 708.31 ± 357.50). Pain was present in 64 patients (62.7%) of all study group; more frequent in women (56.3% vs. 43.8%, p&gt; 0.05), with motor fluctuations (72.4% vs. 27.6%, p&gt; 0.05), with dyskinesia (64.0 % vs. 36.0%, p&gt; 0.05) and restless leg syndrome patients (72.7% vs. 27.3%, p&gt; 0.05). Akinetic-Rigid (0.83 ± 0.80 vs. 0.64 ± 0.56, p&gt; 0.05), and quality of life scores (59.70 ± 25.46 vs. 53.84 ±35.76, p&gt; 0.05) were insignificantly higher in “BP pain + “patients. They had longer disease duration (74.19 ± 39.99 y.o. vs 53.29 ± 41.06 y.o. p=0.017), higher depression (16.36 ± 11.97 vs. 8.09 ± 6.42, p=0.000), psychological (10.28 ±6.20 vs. 4.77 ± 2.82, p=0.000) and non-motor symptoms (66.27 ±39.25 vs. 46.68 ± 32.56, p=0.015) scores. Conclusions: Pain is common in PD, especially in long disease associated with motor complications, depression and other non-motor symptoms.

The impact of dysphagia in Parkinson's disease patients treated with levodopa/carbidopa intestinal gel

BackgroundDysphagia is common in advanced phases of Parkinson disease (PD), and is a risk factor for aspiration pneumonia. Nonetheless, dysphagia has been poorly investigated in PD patients treated with levodopa-carbidopa intestinal gel (LCIG). We aimed to analyze the impact of dysphagia on mortality in LCIG treated patients and its relationship with other PD disability milestones. MethodsWe retrospectively evaluated 95 consecutive PD patients treated with LCIG. Kaplan-Meier and log-rank test were used to compare mortality in patients with dysphagia from others. Cox regression was used to estimate the impact of dysphagia, age, disease duration, and Hoehn and Yahr (H&Y) on mortality in the entire cohort. Finally, univariate and multivariate regression analyses were used to estimate the association between dysphagia and age, disease duration, H&Y, hallucinations, and dementia. ResultsA significantly higher mortality rate was observed in patients with dysphagia. In the Cox model, dysphagia was the only feature significantly associated with mortality (95%CI 2.780–20.609; p < 0.001). Univariate analyses showed a significant correlation between dysphagia and dementia (OR: 0.387; p:0.033), hallucinations (OR: 0.283; p:0.009), and H&Y score (OR: 2.680; p < 0.001); in the multivariate analysis, only the H&Y stage was associated with the presence of dysphagia (OR: 2.357; p:0.003). ConclusionDysphagia significantly increased the risk of death in our cohort of LCIG-treated patients, independently from other relevant features such as age, disease duration, dementia, and hallucinations. These findings support the management of this symptom as a priority in the advanced PD stages, even in people treated with LCIG.

Timely referral for device-aided therapy in Parkinson's disease. Development of a screening tool

BackgroundTimely referral of Parkinson's disease (PD) patients to specialized centers for treatment with device-aided therapies (DAT) is suboptimal. ObjectiveTo develop a screening tool for timely referral for DAT in PD and to compare the tool with the published 5-2-1 criteria. MethodsA cross-sectional, observational study was performed in 8 hospitals in the catchment area of a specialized movement disorder center in the Northern part of the Netherlands. The target population comprised PD patients not yet on DAT visiting the outpatient clinic of participating hospitals. The primary outcome was apparent eligibility for referral for DAT based on consensus by a panel of 5 experts in the field of DAT. Multivariable logistic regression modelling was used to develop a screening tool for eligibility for referral for DAT. Potential predictors were patient and disease characteristics as observed by attending neurologists. ResultsIn total, 259 consecutive PD patients were included, of whom 17 were deemed eligible for referral for DAT (point prevalence: 6.6%). Presence of response fluctuations and troublesome dyskinesias were the strongest independent predictors of being considered eligible. Both variables were included in the final model, as well as levodopa equivalent daily dose. Decision curve analysis revealed the new model outperforms the 5-2-1 criteria. A simple chart was constructed to provide guidance for referral. Discrimination of this simplified scoring system proved excellent (AUC after bootstrapping: 0.97). ConclusionsAwaiting external validation, the developed screening tool already appears promising for timely referral and subsequent treatment with DAT in patients with PD.

Levodopa Equivalent Dose of Safinamide: A Multicenter, Longitudinal, Case-Control Study.

Effects of dopaminergic medications used to treat Parkinson's disease (PD) may be compared with each other by using conversion factors, calculated as Levodopa equivalent dose (LED). However, current LED proposals on MAO-B inhibitors (iMAO-B) safinamide and rasagiline are still based on empirical approaches. To estimate LED of safinamide 50 and 100 mg. In this multicenter, longitudinal, case-control study, we retrospectively reviewed clinical charts of 500 consecutive PD patients with motor complications and treated with (i) safinamide 100 mg (N=130), safinamide 50 mg (N=144), or rasagiline 1 mg (N=97) for 9 ± 3 months and a control group of patients never treated with any iMAO-B (N=129). Major baseline features (age, sex, disease duration and stage, severity of motor signs and motor complications) were similar among the groups. Patients on rasagiline had lower UPDRS-II scores and Levodopa dose than control subjects. After a mean follow-up of 8.8-to-10.1 months, patients on Safinamide 50 mg and 100 mg had lower UPDRS-III and OFF-related UPDRS-IV scores than control subjects, who in turn had larger increase in total LED than the three iMAO-B groups. After adjusting for age, disease duration, duration of follow-up, baseline values and taking change in UPDRS-III scores into account (sensitivity analysis), safinamide 100 mg corresponded to 125 mg LED, whereas safinamide 50 mg and rasagiline 1mg equally corresponded to 100 mg LED. We used a rigorous approach to calculate LED of safinamide 50 and 100 mg. Large prospective pragmatic trials are needed to replicate our findings.

Migraine and Tension-type Headache in Parkinson's Disease and Progressive Supranuclear Palsy/Corticobasal Syndrome.

To compare the prevalence and characteristics of migraine and tension-type headache (TTH) among patients with Parkinson's disease (PD), progressive supranuclear palsy/corticobasal syndrome (PSP/CBS), and healthy controls (HCs). This cross-sectional study involved the collection of data from consecutive PD (n = 81) and PSP/CBS (n = 21) patients along with 104 HCs. Migraine and TTH were diagnosed using the International Classification of Headache Disorders 3rd edition criteria. Demographic data, PD or PSP/CBS details, and the presence and characteristics of migraine and TTH were collected. Montreal Cognitive Assessment Scale, Patient Health Questionnaire-9, and Pittsburgh Sleep-Quality Index were used to assess cognition, depression, and sleep quality, respectively. A comparable proportion of PD and PSP/CBS patients reported lifetime headache (46.9% vs 23.8%; P = 0.06). TTH was more common, observed in 84.3%, 100%, and 93.5% of PD, PSP/CBS, and HCs with lifetime headache, respectively. A comparable proportion of participants in all three groups had bilateral (P = 0.10), dull-aching headache (P = 0.09), and occurring <5/month (P > 0.99). The mean severity score of headache among three groups was comparable (P = 0.39). Although the demographic and clinical characteristics of PSP/CBS patients with and without headache were comparable, PD patients with headache had a higher MDS-UPDRS-III score than those without. More than two-third PD and all PSP/CBS patients with lifetime headache reported headache improvement following parkinsonism onset. The prevalence and characteristics of migraine and TTH were comparable in PD, PSP/CBS, and HCs. Headache was associated with greater motor severity in PD. Following parkinsonism onset, headache improved in the majority of PD and PSP/CBS patients with lifetime headache.

Semiology and determinants of apathy across neurodegenerative motor disorders: A comparison between amyotrophic lateral sclerosis, Parkinson's and Huntington's disease.

The semiology and determinants of apathy are largely unknown across amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), and Huntington's disease (HD), due to both motor and non-motor confounders. This study thus aimed at (1) profiling apathy in ALS, PD, and HD and (2) exploring its clinical determinants. Consecutive ALS (N = 99), PD (N = 73), and HD (N = 25) patients underwent a motor-free assessment of apathy (Dimensional Apathy Scale, DAS), global cognition, anxiety and depression. Function was assessed through disease-specific scales. The DAS was also completed by N = 101 healthy controls (HCs). Between-group comparisons on DAS scores were implemented by covarying for all applicable confounders. Predictive models on DAS scores were built through multiple, stepwise regressions. Parkinson's disease and HD, but not ALS, patients were more apathetic than HCs-with HD patients also selectively showing lower initiation and poorer goal-directed planning than HCs. Higher apathetic features were detected in PD and HD as compared to ALS. Education was a protective factor against apathy in ALS. Anxiety was a risk factor for global apathy in ALS, HD, and to a lesser extent, in PD, whereas, protective only toward affective disintegration in PD and ALS. Cognitive inefficiency was a risk factor toward apathy in both PD and ALS. Depression was a risk factor for executive-related apathy in PD. This study provides unprecedented insights into the heterogeneous semiology and determinants of apathy across ALS, PD, and HD via the DAS, in turn informing clinical practice and research.

Utility of the 20-Item Noise Pareidolia Task (NPT-20) for Assessing Visuoperceptual Disturbances Associated with Complex Visual Hallucinations in Parkinson's Disease.

Complex visual hallucinations (VH) are a common complication of Parkinson's disease (PD). Recent studies have demonstrated relevance of face pareidolia to VH in PD and Lewy body dementia (LBD). This study examined utility of the 20-item Noise Pareidolia Task (NPT-20) in assessing visuoperceptual disturbances associated with VH in PD. Retrospective chart review included 46 consecutive PD patients who completed NPT-20 during clinical neuropsychological evaluation. About half the sample (43%) reported VH. PD with VH made significantly more false-positive pareidolia errors on the NPT-20 (p < 0.0001). A cut-off of 2 errors yielded 40% sensitivity, 100% specificity to VH; cut-off of 1 yielded 75% sensitivity, 81% specificity. NPT-20 was not associated with any other clinical or demographic factor. Across groups, NPT-20 evinced moderate correlations with visuospatial functioning and visual memory. Current findings support utility of the NPT-20 for evaluating visuoperceptual disturbances associated with VH in PD.

Sexual needs and sexual function of patients with Parkinson's disease.

Sexual dysfunction (SD) is a frequent non-motor symptom in Parkinson's disease (PD) that is rarely addressed, and sexual counseling is sporadic. To investigate PD patients' SD and sexual counseling motivation and to propose an interventional strategy for movement disorder specialists. All consecutive PD patients who presented to a movement disorder unit between 2018 and 2019 completed anonymous questionnaires containing the Female Sexual Function Index, the International Index of Erectile Function, and a questionnaire on sexual needs and motivation to receive sexual counseling. The age range of the 100 recruited patients (78 men) was 40-80years, and the mean disease duration was 8.64 ± 6.84years. SD appeared at all PD stages. The presence of SD pre-PD diagnosis significantly predicted SD post-diagnosis in men. Erectile dysfunction was the most common male SD (70%). Women reported frequent SD before PD diagnosis and currently. More than half of the responders (74% of the men and 40% of the women) were motivated to receive sexual counseling. Most of them (77.4%) were in a relationship. The findings of this analysis revealed that most PD patients had experienced SD before being diagnosed with PD and were interested in receiving sexual counseling. We propose a six-step intervention strategy for the management of SD in PD designed for application in a movement disorder unit. We also recommend that neurologists and other healthcare providers undergo training to provide basic sexual counseling tailored to the needs of PD patients.

Predicting Impulse Control Disorders in Parkinson Disease through Incentive Biomarkers.

This study was undertaken to evaluate whether the feedback-related negativity (FRN)-a neurophysiological marker of incentive processing-can be used to predict the development of impulse control disorders (ICDs) in Parkinson disease (PD). The longitudinal cohort consisted of consecutive nondemented PD patients with no ICD history. We recorded FRN signals while they performed a gambling task. We calculated the mean amplitude difference between losses and gains (FRNdiff) to be used as a predictor of future ICD development. We performed prospective biannual follow-up assessments for 30months to detect incident ICDs. Finally, we evaluated how basal FRNdiff was associated with posterior development of ICDs using survival models. Between October 7, 2015 and December 16, 2016, we screened 120 patients. Among them, 94 patients performed the gambling and 92 completed the follow-up. Eighteen patients developed ICDs during follow-up, whereas 74 remained free of ICDs. Baseline FRNdiff was greater in patients who developed ICDs than in those who did not (-2.33μV vs -0.84μV, p= 0.001). No other significant baseline differences were found. The FRNdiff was significantly associated with ICD development in the survival models both when not adjusted (hazard ratio [HR]= 0.73, 95% confidence interval [CI]= 0.58-0.91, p= 0.006) and when controlling for dopamine replacement therapy, sex, and age (HR=0.74, 95% CI=0.55-0.97, p= 0.035). None of the impulsivity measures evaluated was related to ICD development. Reward-processing differences measured by FRN signals precede ICD development in PD. This neurophysiological marker permits identification of patients with high risk of ICD development. ANN NEUROL 2022;92:974-984.

Pre-operative cognitive burden as predictor of motor outcome following bilateral subthalamic nucleus deep brain stimulation in Parkinson's disease.

The interrelationship between neurocognitive impairments and motor functions was observed in patients with advanced Parkinson's disease (PD). This study was conducted to identify pre-operative neurocognitive and clinical predictors of short-term motor outcome following subthalamic nucleus deep brain stimulation (STN-DBS). All consecutive PD patients who were eligible for bilateral STN-DBS from 2009 to 2019 were evaluated before and at 1year following surgery. Standard motor evaluation and neurocognitive tests including global cognition, memory, executive functions (attention and category fluency), confrontational speech, visuospatial abilities, and mood were conducted at baseline. The post-operative STN-DBS effects were assessed at 1year following the surgery. Multiple regression analysis was applied to identify baseline independent predictors of post-operative STN-DBS effect. A total of 82 patients were analyzed. It was found that younger age at operation, higher levodopa responsiveness at baseline based on UPDRS-III total score, and better baseline verbal delayed memory and category fluency predicted post-operative motor outcome at 1year following STN-DBS (F = 9.639, p < 0.001, R2 = .340). Our findings demonstrated the role of baseline cognitive burden, especially cognitive processes related to frontostriatal circuits, was significant clinical predictors of short-term motor outcomes following STN-DBS. Profile analysis of neurocognitive functions at baseline is recommended.