Non-demented Parkinson's Disease Patients Research Articles

Reliable change indices for the Italian version of the Montreal Cognitive Assessment (MoCA) in non-demented Parkinson’s disease patients

Background. The present study aimed at deriving regression-based reliable change indices (RCIs) for the Montreal Cognitive Assessment (MoCA) in an Italian cohort of non-demented Parkinson’s disease (PD) patients.MethodsN = 33 consecutive, non-demented PD patients were followed-up at a 5-to-8-month interval (M = 6.6; SD = 0.6) with the MoCA. Practice effects and test-retest reliability were assessed via dependent-sample t-tests and intra-class correlation (ICC) coefficients, respectively. RCIs were derived separately for raw and demographically adjusted MoCA scores according to a standardized regression-based approach by accounting for both baseline confounders (i.e., demographics, disease duration and Unified Parkinson’s Disease Rating Scale scores) and retest interval.ResultsNo practice effects were found (t(32) = 0.29; p = .778), with acceptable test-retest reliability being detected (ICC = 0.67). MoCA scores at T0 proved to be the only significant predictor of T1 MoCA performances within both the model addressing raw scores and that addressing adjusted scores (ps < 0.001).ConclusionsThe present study provides Italian practitioners and researchers with regression-based RCIs for the MoCA in non-demented PD patients, which can be reliably adopted for retest interval ≥ 5 and ≤ 8 months without encountering any practice effect.

Correlation between dopaminergic and metabolic asymmetry in Lewy body disease – A dual-imaging study

IntroductionThe a-Synuclein Origin and Connectome (SOC) model of Lewy body diseases postulates that a-syuclein will be asymmetrically distributed in some patients with Lewy body diseases, potentially leading to asymmetric neuronal dysfunction and symptoms. MethodsWe included two patient groups: 19 non-demented Parkinson's disease (nPD) patients with [18F]FDG PET and motor symptoms assessed by UPDRS-III, and 65 Lewy body dementia (LBD) patients with [18F]FDG PET and dopamine radioisotope imaging. Asymmetry indices were calculated for [18F]FDG PET by including the cortex for each hemisphere, for dopamine radioisotope imaging by including the putamen and caudate separately, and for motor symptoms by using the difference between right-left UPDRS-III score. Correlations between these asymmetry indices were explored to test the predictions of the SOC model. To identify cases with a more typical LBD imaging profile, we calculated a Cingulate Island Sign (CIS) index on the [18F]FDG PET image. ResultsWe found a significant correlation between cortical interhemispheric [18F]FDG asymmetry and motor-symptom asymmetry in nPD patients (r = 0.62, P = 0.004). In patients with LBD, we found a significant correlation between cortical interhemispheric [18F]FDG asymmetry and dopamine transporter asymmetry in the caudate (r = 0.37, P = 0.0019), but not in the putamen (r = 0.15, P = 0.22). We observed that the correlation in the caudate was stronger in LBD subjects with the highest CIS index, i.e., with more typical LBD imaging profiles. ConclusionOur study partly supports the SOC model, but further investigations are needed – ideally of de novo, non-demented PD patients.

Effects of Biodanza® SRT on Motor, Cognitive, and Behavioral Symptoms in Patients with Parkinson's Disease: A Randomized Controlled Study.

Rolando Toro's Biodanza (SRT) is a therapeutic strategy that uses movement, music, and emotions to induce integrative living experiences. The present study aims to explore the efficacy of a three-month SRT intervention on motor, cognitive, and behavioral symptoms in patients with Parkinson's disease (PD). This study employed a randomized between-group design. Twenty-eight non-demented PD patients were enrolled in this study. Out of these, fourteen patients were assigned to the active treatment group using the Biodanza SRT system and fourteen to the untreated control group. The study group attended 2 h SRT classes once a week, completing twelve lessons in twelve weeks. All patients underwent: (i) a neurological examination to measure the severity of motor symptoms, balance, mobility, and risk of falls, and (ii) a neuropsychological battery to assess cognitive status, apathy, depressive symptomatology, and perceived quality of life (QoL), at study entry (T0) and at twelve weeks (T1, end of dance training). At T1, we observed a significant improvement in motor (i.e., severity of motor symptoms and balance) and cognitive parameters (i.e., working memory and delayed verbal memory) in all treated patients compared with the controls. Furthermore, a significant improvement in the social support dimension was found in all treated patients compared to the controls. A trend toward increased apathy was found in untreated patients at T1. The three-month Biodanza intervention significantly ameliorated the motor parameters of PD patients, with a parallel improvement in cognitive and QoL status. Hence, Biodanza intervention can, in the short term, represent a useful personalized medical intervention for the management of Parkinson's disease.

A multi-site study on sex differences in cortical thickness in non-demented Parkinson’s disease

Clinical, cognitive, and atrophy characteristics depending on sex have been previously reported in Parkinson’s disease (PD). However, though sex differences in cortical gray matter measures in early drug naïve patients have been described, little is known about differences in cortical thickness (CTh) as the disease advances. Our multi-site sample comprised 211 non-demented PD patients (64.45% males; mean age 65.58 ± 8.44 years old; mean disease duration 6.42 ± 5.11 years) and 86 healthy controls (50% males; mean age 65.49 ± 9.33 years old) with available T1-weighted 3 T MRI data from four international research centers. Sex differences in regional mean CTh estimations were analyzed using generalized linear models. The relation of CTh in regions showing sex differences with age, disease duration, and age of onset was examined through multiple linear regression. PD males showed thinner cortex than PD females in six frontal (bilateral caudal middle frontal, bilateral superior frontal, left precentral and right pars orbitalis), three parietal (bilateral inferior parietal and left supramarginal), and one limbic region (right posterior cingulate). In PD males, lower CTh values in nine out of ten regions were associated with longer disease duration and older age, whereas in PD females, lower CTh was associated with older age but with longer disease duration only in one region. Overall, male patients show a more widespread pattern of reduced CTh compared with female patients. Disease duration seems more relevant to explain reduced CTh in male patients, suggesting worse prognostic over time. Further studies should explore sex-specific cortical atrophy trajectories using large longitudinal multi-site data.

Diagnostic value of vietnamese smell identification test in Parkinson's disease

IntroductionThe Vietnamese Smell Identification Test (VSIT) has been validated in determining olfactory dysfunction in the Vietnamese population; however, its value in diagnosing Parkinson's disease (PD) has not been established. MethodsThis case-control study was conducted at University Medical Center HCMC, Ho Chi Minh City, Vietnam. The study sample included non-demented PD patients and healthy controls (HC) who were gender- and age-matched. All participants were evaluated for odor identification ability using the VSIT and the Brief Smell Identification Test (BSIT). ResultsA total of 218 HCs and 218 PD patients participated in the study. The median VSIT and BSIT scores were significantly different between PD and HC groups (VSIT, 5 (3) vs. 9 (2), P < 0.0001; BSIT, 6 (3) vs 8 (2), P < 0.0001). Using the cut-off of <8 for correct answers out of 12 odorants, the VSIT had higher sensitivity (84.4%) and specificity (86.2%) than those of the BSIT (sensitivity of 81.7% and specificity of 69.3%) for the diagnosis of PD. The area under the curve (AUC) value was greater for the VSIT than for the BSIT (0.909 vs 0.818). The smell identification scores were not significantly correlated with disease duration, disease severity, or LEDD (all p > 0.05). ConclusionThe VSIT can be a valuable ancillary tool for supporting the diagnosis of PD in Vietnam. Olfactory dysfunction in PD was unrelated to the disease duration and severity. The VSIT can be applied to improve the accuracy of clinical PD diagnosis.

Psychometrics and diagnostics of the Italian version of the Alternate Verbal Fluency Battery (AVFB) in non-demented Parkinson's disease patients.

Verbal fluency (VF) tasks are known as suitable for detecting cognitive impairment (CI) in Parkinson's disease (PD). This study thus aimed to evaluate the psychometrics and diagnostics of the Alternate Verbal Fluency Battery (AVFB) by Costa et al. (2014) in an Italian cohort of non-demented PD patients, as well as to derive disease-specific cut-offs for it. N = 192 non-demented PD patients were screened with the Montreal Cognitive Assessment (MoCA) and underwent the AVFB-which includes phonemic, semantic and alternate VF tests (PVF; SVF; AVF), as well as a Composite Shifting Index (CSI) reflecting the "cost" of shifting from a single- to a double-cued VF task. Construct validity and diagnostics were assessed for each AVFB measure against the MoCA. Internal reliability and factorial validity were also tested. The MoCA proved to be strongly associated with PVF, SVF and AVF scores, whilst moderately with the CSI. The AVFB was internally consistent and underpinned by a single component; however, an improvement in both internal reliability and fit to its factorial structure was observed when dropping the CSI. Demographically adjusted scores on PVF, SVF and AVF tests were diagnostically sound in detecting MoCA-defined cognitive impairment, whilst this was not true for the CSI. Disease-specific cut-offs for PVF, SVF and AVF tests were derived. In conclusion, PVF, SVF and AVF tests are reliable, valid and diagnostically sound instruments to detect cognitive impairment in non-demented PD patients and are therefore recommended for use in clinical practice and research.

Electrophysiological signatures of anxiety in Parkinson’s disease

Anxiety is a common non-motor symptom in Parkinson’s disease (PD) occurring in up to 31% of the patients and affecting their quality of life. Despite the high prevalence, anxiety symptoms in PD are often underdiagnosed and, therefore, undertreated. To date, functional and structural neuroimaging studies have contributed to our understanding of the motor and cognitive symptomatology of PD. Yet, the underlying pathophysiology of anxiety symptoms in PD remains largely unknown and studies on their neural correlates are missing. Here, we used resting-state electroencephalography (RS-EEG) of 68 non-demented PD patients with or without clinically-defined anxiety and 25 healthy controls (HC) to assess spectral and functional connectivity fingerprints characterizing the PD-related anxiety. When comparing the brain activity of the PD anxious group (PD-A, N = 18) to both PD non-anxious (PD-NA, N = 50) and HC groups (N = 25) at baseline, our results showed increased fronto-parietal delta power and decreased frontal beta power depicting the PD-A group. Results also revealed hyper-connectivity networks predominating in delta, theta and gamma bands against prominent hypo-connectivity networks in alpha and beta bands as network signatures of anxiety in PD where the frontal, temporal, limbic and insular lobes exhibited the majority of significant connections. Moreover, the revealed EEG-based electrophysiological signatures were strongly associated with the clinical scores of anxiety and followed their progression trend over the course of the disease. We believe that the identification of the electrophysiological correlates of anxiety in PD using EEG is conducive toward more accurate prognosis and can ultimately support personalized psychiatric follow-up and the development of new therapeutic strategies.

17 Grit Predicts Lower Cognitive Fatigue in Persons with Parkinson’s Disease Independent of Cognitive Status

Objective:Fatigue, which can be classified into physical and cognitive subtypes (Schiehser et al., 2012), is a common non-motor symptom in persons with Parkinson’s disease (PD) that has no clear treatment. Cognitive changes, also common in PD (Litvan et al., 2012), may impact how patients perceive fatigue (Kukla et al., 2021). Grit is a personality trait defined as perseverance and passion towards a long-term goal, and is associated with multiple positive outcomes such as lower fatigue levels in healthy individuals (Martinez-Moreno et al., 2021). However, scarce research has examined the relationship between grit and fatigue in persons with PD. Therefore, we aimed to investigate the relationship between fatigue (cognitive and physical) and grit, as well as the impact of cognitive status (i.e., cognitive normal vs. mild cognitive impairment [MCI]) on this relationship in non-demented individuals with PD.Participants and Methods:Participants were 70 non-demented individuals with PD who were diagnosed as either cognitively normal (n=20) or MCI (n=50) based on Level II of the Movement Disorder Society PD-MCI criteria. Participants completed the Modified Fatigue Impact Scale (MFIS), which consists of two subscales (cognitive and physical fatigue) that are combined for a total overall fatigue score. Participants also completed the Grit Scale, which consists of items such as ambition, perseverance, and consistency. ANOVAs were conducted to determine differences in grit between PD-cognitively normal vs PD-MCI groups. Correlations and multiple hierarchical regressions controlling for significant demographics (i.e., age, education, sex), mood (i.e., depression, anxiety) and disease variables (i.e., disease duration, Levodopa equivalent dosage) with backwards elimination were conducted to evaluate the relationship between grit and fatigue (MFIS total score and MFIS cognitive and physical fatigue subscales).Results:There was no significant difference in grit total scores between PD patients who were cognitively normal or MCI (p = .336). Higher grit total scores predicted lower MFIS total (ß = -.290, p = .005) and lower cognitive fatigue (ß = -.336, p &lt; .001) scores in the total sample, above and beyond relevant covariates as well as cognitive status. Grit scores were not significantly associated with physical fatigue (ß = -.206, p = .066). Furthermore, cognitive status was not a significant predictor of fatigue scores in any of the models (all p’s &gt; .28).Conclusions:Findings indicate that higher levels of grit are associated with lower levels of fatigue, specifically cognitive fatigue, in individuals with PD. These results held true for those who were cognitively normal or with MCI, suggesting that grit may impact fatigue in non-demented PD patients regardless of cognitive status. These findings underscore the importance of considering grit when assessing or treating fatigue, particularly cognitive fatigue, in persons with PD.

Brain hypometabolism in non-demented microtubule-associated protein tau H1 carriers with Parkinson's disease.

The microtubule-associated protein tau (MAPT) H1 homozygosity (H1/H1 haplotype) is a genetic risk factor for neurodegenerative diseases, such as Parkinson's disease (PD). MAPT H1 homozygosity has been associated with conversion to PD; however, results are conflicting since some studies did not find a strong influence. Cortical hypometabolism is associated with cognitive impairment in PD. In this study, we aimed to evaluate the metabolic pattern in nondemented PD patients MAPT H1/H1 carriers in comparison with MAPT H1/H2 haplotype. In addition, we evaluated domain-specific cognitive differences according to MAPT haplotype. We compared a group of 26 H1/H1 and 20 H1/H2 carriers with late-onset PD. Participants underwent a comprehensive neuropsychological cognitive evaluation and a [18F]-Fluorodeoxyglucose PET-MR scan. MAPT H1/H1 carriers showed worse performance in the digit span forward test of attention compared to MAPT H1/H2 carriers. In the [18F]-Fluorodeoxyglucose PET comparisons, MAPT H1/H1 displayed hypometabolism in the frontal cortex, parahippocampal, and cingulate gyrus, as well as in the caudate and globus pallidus. PD patients MAPT H1/H1 carriers without dementia exhibit relative hypometabolism in several cortical areas as well as in the basal ganglia, and worse performance in attention than MAPT H1/H2 carriers. Longitudinal studies should assess if lower scores in attention and dysfunction in these areas are predictors of dementia in MAPT H1/H1 homozygotes.

Anxiety in Parkinson's Disease Is Associated with Changes in Brain Structural Connectivity.

Anxiety in Parkinson's disease (PD) has been associated with grey matter changes and functional changes in anxiety-related neuronal circuits. So far, no study has analyzed white matter (WM) changes in patients with PD and anxiety. The aim of this study was to identify WM changes by comparing PD patients with and without anxiety, using diffusion-tensor imaging (DTI). 108 non-demented PD patients with (n = 31) and without (n = 77) anxiety as defined by their score on the Parkinson Anxiety Scale participated. DTI was used to determine the fractional anisotropy (FA) and mean diffusivity (MD) in specific tracts within anxiety-related neuronal circuits. Mean FA and MD were compared between groups and correlated with the severity of anxiety adjusted by sex, center, Hoehn & Yahr stage, levodopa equivalent daily dosage, and Hamilton depression rating scale. Compared to patients without anxiety, PD patients with anxiety showed lower FA within the striato-orbitofrontal, striato-cingulate, cingulate-limbic, and caudate-thalamic tracts; higher FA within the striato-limbic and accumbens-thalamic tracts; higher MD within the striato-thalamic tract and lower MD within the striato-limbic tract. Anxiety in PD is associated with microstructural alterations in anxiety-related neuronal circuits within the WM. This result reinforces the view that PD-related anxiety is linked to structural alteration within the anxiety-related brain circuits.

Atypical brain FDG-PET patterns increase the risk of long-term cognitive and motor progression in Parkinson's disease

IntroductionBrain hypometabolism patterns have been previously associated with cognitive decline in Parkinson's disease (PD). Our aim is to evaluate the impact of single-subject fluorodeoxyglucose (FDG)-PET brain hypometabolism on long-term cognitive and motor outcomes in PD. MethodsForty-nine non-demented PD patients with baseline brain FDG-PET data underwent an extensive clinical follow-up for 8 years. The ability of FDG-PET to predict long-term cognitive and motor progression was evaluated using Cox regression and mixed ANCOVA models. ResultsParticipants were classified according to FDG-PET pattern in PD with typical (n = 26) and atypical cortical metabolism (n = 23). Patients with atypical brain hypometabolic patterns showed higher incidence of dementia (60% vs 3%; HR = 18.3), hallucinations (56% vs 7%, HR = 7.3) and faster motor decline compared to typical pattern group. ConclusionThis study argues for specific patterns of FDG-PET cortical hypometabolism in PD as a prognostic marker for long term cognitive and motor outcomes at single-subject level.

Diffusion and structural MRI as potential biomarkers in people with Parkinson's disease and cognitive impairment.

To explore the neuroimage change in Parkinson's disease (PD) patients with cognitive impairments, this study investigated the correlation between plasma biomarkers and morphological brain changes in patients with normal cognition and mild cognitive impairment. The objective was to identify the potential target deposition regions of the plasma biomarkers and to search for the relevant early neuroimaging biomarkers on the basis of different cognitive domains. Structural brain MRI and diffusion weighted images were analyzed from 49 eligible PD participants (male/female: 27/22; mean age: 73.4 ± 8.5years) from a retrospective analysis. Plasma levels of α-synuclein, amyloid beta peptide, and total tau were collected. A comprehensive neuropsychological assessment of the general and specific cognitive domains was performed. Difference between PD patients with normal cognition and impairment was examined. Regression analysis was performed to evaluate the correlation between image-derived index and plasma biomarkers or neuropsychological assessments. Significant correlation was found between plasma Aβ-42 level and fractional anisotropy of the middle occipital, angular, and middle temporal gyri of the left brain, as well as plasma T-tau level and the surface area of the isthmus or the average thickness of the posterior part of right cingulate gyrus. Visuospatial and executive function is positively correlated with axial diffusivity in bilateral cingulate gyri. In nondemented PD patients, the target regions for plasma deposition might be located in the cingulate, middle occipital, angular, and middle temporal gyri. Changes from multiple brain regions can be correlated to the performance of different cognitive domains. Cognitive impairment in Parkinson's disease is primarily linked to biomarkers associated with Alzheimer's disease rather than those related to Parkinson's disease and resembles the frontal variant of Alzheimer's disease, which may guide management strategies for cognitive impairment in Parkinson's disease. • Fractional anisotropy, surface area, and thickness in the cingulate, middle occipital, angular, and middle temporal gyri can be significantly correlated with plasma Aβ-42 and T-tau level. • Axial diffusivity in the cingulate gyri was correlated with visuospatial and executive function. • The pattern of cognitive impairment in Parkinson's disease can be similar to the frontal variant than typical Alzheimer's disease.

Validity and diagnostics of the Italian version of the Montreal Cognitive Assessment (MoCA) in non-demented Parkinson’s disease patients

BackgroundThis study aimed at: (1) assessing, in an Italian cohort of non-demented Parkinson’s disease (PD) patients, the construct validity of the Montreal Cognitive Assessment (MoCA) against both first- and second-level cognitive measures; (2) delivering an exhaustive and updated evaluation of its diagnostic properties.MethodsA retrospective cohort of N = 237 non-demented PD patients having been administered the MoCA was addressed, of whom N = 169 further underwent the Mini-Mental State Examination (MMSE) and N = 68 the Parkinson’s Disease Cognitive Rating Scale (PD-CRS). A subsample (N = 60) also underwent a second-level cognitive battery encompassing measures of attention/executive functioning, language, memory, praxis and visuo-spatial abilities. Construct validity was assessed against both the PD-CRS and the second-level cognitive battery. Diagnostics were tested via receiver-operating characteristics analyses against a below-cut-off MMSE score.ResultsThe MoCA was associated with both PD-CRS scores (p < .001) and the vast majority of second-level cognitive measures (ps < .003). Both raw and adjusted MoCA scores proved to be highly accurate to the aim of identifying patients with MMSE-confirmed cognitive dysfunctions. A MoCA score adjusted for age and education according to the most recent normative dataset and < 19.015 is herewith suggested as indexing cognitive impairment in this population (AUC = .92; sensitivity = .92; specificity = .80).DiscussionThe Italian MoCA is a valid and diagnostically sound screener for global cognitive inefficiency in non-demented PD patients. Further studies are nevertheless needed that confirm its diagnostic values against a measure other than the MMSE.

Identifying key multi-modal predictors of incipient dementia in Parkinson's disease: a machine learning analysis and Tree SHAP interpretation.

Persons with Parkinson's disease (PD) differentially progress to cognitive impairment and dementia. With a 3-year longitudinal sample of initially non-demented PD patients measured on multiple dementia risk factors, we demonstrate that machine learning classifier algorithms can be combined with explainable artificial intelligence methods to identify and interpret leading predictors that discriminate those who later converted to dementia from those who did not. Participants were 48 well-characterized PD patients (Mbaseline age = 71.6; SD = 4.8; 44% female). We tested 38 multi-modal predictors from 10 domains (e.g., motor, cognitive) in a computationally competitive context to identify those that best discriminated two unobserved baseline groups, PD No Dementia (PDND), and PD Incipient Dementia (PDID). We used Random Forest (RF) classifier models for the discrimination goal and Tree SHapley Additive exPlanation (Tree SHAP) values for deep interpretation. An excellent RF model discriminated baseline PDID from PDND (AUC = 0.84; normalized Matthews Correlation Coefficient = 0.76). Tree SHAP showed that ten leading predictors of PDID accounted for 62.5% of the model, as well as their relative importance, direction, and magnitude (risk threshold). These predictors represented the motor (e.g., poorer gait), cognitive (e.g., slower Trail A), molecular (up-regulated metabolite panel), demographic (age), imaging (ventricular volume), and lifestyle (activities of daily living) domains. Our data-driven protocol integrated RF classifier models and Tree SHAP applications to selectively identify and interpret early dementia risk factors in a well-characterized sample of initially non-demented persons with PD. Results indicate that leading dementia predictors derive from multiple complementary risk domains.

Clinimetrics and feasibility of the Italian version of the Frontal Assessment Battery (FAB) in non-demented Parkinson's disease patients.

This study aimed at assessing the cross-sectional and longitudinal clinimetrics and feasibility of the Frontal Assessment Battery (FAB) in non-demented Parkinson's disease (PD) patients. N = 109 PD patients underwent the FAB and the Montreal Cognitive Assessment (MoCA). A subsample of patients further underwent a thorough motor, functional and behavioral evaluation (the last including measures of anxiety, depression and apathy). A further subsample was administered a second-level cognitive battery tapping on attention, executive functioning, language, memory, praxis and visuo-spatial abilities. The following properties of the FAB were tested: (1) concurrent validity and diagnostics against the MoCA; (2) convergent validity against the second-level cognitive battery; (4) association with motor, functional and behavioral measures; (5) capability to discriminate patients from healthy controls (HCs; N = 96); (6) assessing its test-retest reliability, susceptibility to practice effects and predictive validity against the MoCA, as well as deriving reliable change indices (RCIs) for it, at a ≈ 6-month interval, within a subsample of patients (N = 33). The FAB predicted MoCA scores at both T0 and T1, converged with the vast majority of second-level cognitive measures and was associated with functional independence and apathy. It accurately identified cognitive impairment (i.e., a below-cut-off MoCA score) in patients, also discriminating patients from HCs. The FAB was reliable at retest and free of practice effects; RCIs were derived according to a standardized regression-based approach. The FAB is a clinimetrically sound and feasible screener for detecting dysexecutive-based cognitive impairment in non-demented PD patients.

Natural IgG antibodies to β amyloid are decreased in patients with Parkinson’s disease

Natural antibodies (nAbs) against aggregation-prone proteins have been found in healthy normal subjects. These proteins likely have a pathogenetic role in neurodegenerative diseases of ageing. They include the amyloid β (Aβ) protein which may play an important role in Alzheimer’s dementia (AD), and α-synuclein, a major determinant of Parkinson’s disease (PD). We measured nAbs to Aβ in a group of Italian patients with AD, vascular dementia, non-demented PD patients and healthy elderly controls. We found that Aβ antibody levels in AD were similar to age- and sex-matched controls, but contrary to our expectations, they were significantly reduced in PD. This may identify patients that could be more prone to amyloid aggregation.

Phantom Boarder Relates to Experimentally-Induced Presence Hallucinations in Parkinson's Disease.

Phantom boarder (PB) is the sensation that someone uninvited is in the patient's home despite evidence to the contrary. It is mostly reported by patients with neurodegenerative disorders such as Alzheimer's disease, dementia with Lewy bodies or Parkinson's disease (PD). Presence hallucination (PH) is frequent in neurodegenerative disease, shares several aspects with PB, and is the sensation that someone is nearby, behind or next to the patient (when nobody is actually there). Recent work developed a sensorimotor method to robotically induce PH (robot-induced PH, riPH) and demonstrated that a subgroup of PD patients showed abnormal sensitivity for riPH. We investigated if PD patients with PB (PD-PB) would (1) show elevated sensitivity for riPH that (2) is comparable to that of patients reporting PH, but not PB (PD-PH). We studied the sensitivity of non-demented PD patients in a sensorimotor stimulation paradigm, during which three groups of patients (PD-PB; PD-PH; PD patients without hallucinations, PD-nPH) were exposed to different conditions of conflicting sensorimotor stimulation. We show that PD-PB and PD-PH groups had a higher sensitivity to riPH (compared to PD-nPH). PD-PB and PD-PH groups did not differ in riPH sensitivity. Together with interview data, these behavioral data on riPH show that PB is associated with PH, suggesting that both share some underlying brain mechanisms, although interview data also revealed phenomenological differences. Because PD-PB patients did not suffer from dementia nor delusions, we argue that these shared mechanisms are of perceptual-hallucinatory nature, involving sensorimotor signals and their integration.

Characteristics of behavioural addiction in Parkinson’s disease patients with self-reported impulse control disorder and controls matched for levodopa equivalent dose: a matched case–control study

Impulse control disorders (ICD) in Parkinson’s disease (PD) frequently occur, not always as a direct consequence of dopaminergic medication. This study investigated premorbid personality traits and behavioural characteristics in non-demented PD patients with self-reported symptoms of ICD (PD-srICD). From a total of 200 non-demented PD patients who filled out questionnaires assessing symptoms and severity of ICD, those were classified as PD-srICD (n = 32) who reported current occurrence of at least one compulsive behaviour (gambling, sexual behaviour, buying behaviour, or eating). As a control group, 32 patients with no self-reported ICD symptoms were matched for levodopa equivalent daily dose. The demographic, clinical, and premorbid personality profiles were compared between both groups. Frequency of psychological characteristics indicating substance use disorder was evaluated in patients with PD-srICD. Patients with PD-srICD were more frequently male, younger at examination, had earlier PD onset, more depression, higher non-motor burden, less quality of life (p < 0.05, respectively), and more frequently reported premorbid sensation seeking/novelty orientation (p = 0.03) and joyful experience of stress (p = 0.04) than patients in the control group. Of patients with PD-srICD, 90.6% reported at least one behavioural characteristic of substance use disorder, most frequently positive expectations following ICD behaviour and illusional beliefs about its behavioural control. Signs of addiction were common among patients with PD-srICD. Therefore, the profile of psychological characteristics in patients with PD-srICD resembled that of patients with substance use disorder. It can be concluded that dopamine replacement therapy (DRT) alone does not account for PD-srICD and that thorough psychological diagnostics are recommended.

NIMHANS Neuropsychological Battery for Elderly in Parkinson's Disease Patients: Validation and Diagnosis using MDS PD-MCI Task Force Criteria in Indian Population.

Cognitive impairment is a common non-motor feature of Parkinson's Disease (PD). Diagnosis of mild cognitive impairment is challenging and routinely missed in clinical practice. Our study aimed to study the efficacy of NIMHANS Neuropsychological Battery for Elderly (NNB-E) in diagnosing subtle cognitive deficits in PD patients. The aim of this study is to validate NNB-E and evaluate cognitive impairment in PD patients in comparison with healthy controls. We recruited 31 PD patients and 31 healthy controls in the current study. We validated NNB-E using receiver operating characteristic (ROC) curve analysis, Crohnbach's alpha, principal component analysis, and Pearson product-moment correlation, and studied the cognitive impairments using NNB-E in the non-demented PD patients and controls who scored ≥24 on HMSE. Cognitive performance of PD patients was poor compared to controls. NNB-E showed good internal consistency and construct validity with Crohnbach's alpha of 0.861 and area under the curve (AUC) of 0.878. The battery was able to detect mild cognitive impairment in 74.1% of patients and 6.4% of controls. The ROC curve showed that the overall sensitivity of the battery was 73.2% and specificity was 92.6% at an optimal cutoff score. Different cutoff values set for defining PD-MCI as per MDS task force criteria resulted in varying frequencies of MCI ranging from 25.8% to 71%. Our study established the validity of NNB-E in PD patients, and this tool was suitable for diagnosing PD-MCI and discriminating PD patients from normal controls in the Indian population. This study also showed PD-MCI at various cutoff scores with greater impairment in executive and attention domains.

Mapping Cholinergic Synaptic Loss in Parkinson's Disease: An [18F]FEOBV PET Case-Control Study.

Cholinergic degeneration is strongly associated with cognitive decline in patients with Parkinson's disease (PD) but may also cause motor symptoms and olfactory dysfunction. Regional differences are striking and may reflect different PD related symptoms and disease progression patterns. To map and quantify the regional cerebral cholinergic alterations in non-demented PD patients. We included 15 non-demented PD patients in early-moderate disease stage and 15 age- and sex-matched healthy controls for [18F]FEOBV positron emission tomography imaging. We quantitated regional variations using VOI-based analyses which were supported by a vertex-wise cluster analysis. Correlations between imaging data and clinical and neuropsychological data were explored. We found significantly decreased [18F]FEOBV uptake in global neocortex (38%, p = 0.0002). The most severe reductions were seen in occipital and posterior temporo-parietal regions (p < 0.0001). The vertex-wise cluster analysis corroborated these findings. All subcortical structures showed modest non-significant reductions. Motor symptoms (postural instability and gait difficulty) and cognition (executive function and composite z-score) correlated with regional [18F]FEOBV uptake (thalamus and cingulate cortex/insula/hippocampus, respectively), but the correlations were not statistically significant after multiple comparison correction. A strong correlation was found between interhemispheric [18F]FEOBV asymmetry, and motor symptom asymmetry of the extremities (r = 0.84, p = 0.0001). Cortical cholinergic degeneration is prominent in non-demented PD patients, but more subtle in subcortical structures. Regional differences suggest uneven involvement of cholinergic nuclei in the brain and may represent a window to follow disease progression. The correlation between asymmetric motor symptoms and neocortical [18F]FEOBV asymmetry indicates that unilateral cholinergic degeneration parallels ipsilateral dopaminergic degeneration.