Non-demented Patients Research Articles

Savremena dijagnoza alchajmerove bolesti - značaj različitih biomarkera korespondencija sa autorom

In preparation for the approval of new therapies for Alzheimer's disease (AD), a key step is the selection, validation and application of screening tests for disease detection and treatment monitoring. Biomarkers for AD have significantly advanced the field in several ways and hold promise for early diagnosis, determination of pathology, and measurement of response to treatment. The classic pathophysiological features of AD (beta-amyloid Ab (A), tau (T) and neurodegeneration (N) can be determined in the cerebrospinal fluid (CSF), but their presence can also be demonstrated by different imaging techniques such as Positron Emission Tomography (PET), either with an amyloid marker or with tau-ligand as the gold standards of amyloid and tau pathology, in trials in clinical practice. Currently, there are no widely accepted blood tests for neuroinflammation, astrocytic, microglial activation in AB. However, both methods are either invasive and/or very expensive at the same time, so great efforts have been made to determine basic and more specific biomarkers in blood as a less invasive and more accessible procedure. In the primary health care setting, diagnostic algorithms from blood could already be sufficient to improve the accuracy of the clinical diagnosis of AB dementia and to positively influence the future treatment and care of people with cognitive problems. Additional studies are needed to evaluate the optimal combination of plasma biomarkers with other accessible and cost-effective procedures, such as, for example, MRI and cognitive tests, which are necessary for further development of predictive algorithms, which will be especially important in non-demented patients with cognitive problems.

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.

Assessment of the safety and clinical efficacy of the Brainmax in therapy of non-demented patients with a mild cognitive impairment

The assessment of the clinical efficiency and safety of the drug Brainmax and its influence on the degree of functional recovery in the treatment of patients with non-dementia cognitive disorders with this drug. An open multicenter randomized study included 60 patients of 18-55 years with light and moderate CI, having complaints of the cognitive spectrum. They used a clinical and neurological study using generally accepted scales and tests (MoCA, MMSE, MFI-20 tests, Schulta, DSST tests and an assessment of the quality of life of SF-36). Patients were randomized in two groups comparable by age and gender. Group 1 was treated with Brainmax per os twice every day for 14 days. After 10-days rest they received same medication for another 14 days. Group 2 was treated with Brainmax per os twice every day for 14 days, without the continuation. The total duration of the study was 40 days, the assessment of their condition was carried out on the 1st day (visit 1), after 15 days (visit 2) and after 40 days (visit 3) using the indicators of the above scales and tests in comparison with the background data. Safety assessment was carried out by the presence and structure of undesirable phenomena. The use of Brainmax led to a significant improvement in cognitive performance according to all generally accepted scales and tests (concentration and maintaining of attention, working memory, visual-constructive skills, volume and speed of attention speed, information processing and executive functions), as well as to the decrease severity of asthenia and improvement of the quality of life. Brainmax has shown a good safety profile, tolerability and clinical efficacy in the treatment of young and middle-aged patients with non-demented cognitive impairment. Significant improvement was observed both with single and double course administration of the drug, but a significantly better effect was noted after its repeated course, which reflects, among other things, the cumulative effect of the active substances of this drug and makes longer use of the drug Brainmax justified and appropriate in these categories of patients. The data obtained allow us to recommend the wider use of the drug Brainmax in clinical practice for the treatment of CI in patients of different ages, which will optimize therapy and improve the course and outcome of the disease.

Clinimetrics of the cognitive section of the Italian ALS Cognitive Behavioral Screen (ALS-CBS™).

The present study aimed at (1) providing further validity and reliability evidence for the Italian version of the cognitive section of the ALS Cognitive Behavioral Screen (ALS-CBS™) and (2) testing its diagnostics within an Italian ALS cohort, as well as at (3) exploring its capability to discriminate patients from healthy controls (HCs). N = 293 non-demented ALS patients were administered the cognitive sections of the ALS-CBS™ and Edinburgh Cognitive and Behavioural ALS Screen (ECAS). N = 96 HCs demographically matched with N = 96 patients were also administered the cognitive section of the ALS-CBS™. In patients, factorial and construct validity, internal reliability, and diagnostics against a defective score on the cognitive section of the ECAS were tested. Case-control discrimination was assessed via a logistic regression. ALS-CBS™ cognitive subscales were underpinned by a simple, unidimensional structure, internally reliable (McDonald's ω = 0.74), and mostly related with ECAS executive and fluency scores (rs = 0.54-0.71). Both raw and age- and education-adjusted scores on the cognitive section of the ALS-CBS™ accurately detected ECAS-defined cognitive impairment (AUC = 0.80 and .88, respectively), yielding optimal error-based, information-based and unitary diagnostics. A cut-off of < 15.374 was identified on adjusted scores. The test was able to discriminate patients from HCs (p < 0.001). The cognitive section of the Italian ALS-CBS™ is a valid, reliable, and diagnostically sound ALS-specific screener for detecting frontotemporal, executive-/attentive-based cognitive inefficiency in non-demented ALS patients, being also able to discriminate them from normotypical individuals.

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.

Prevalence and determinants of language impairment in non-demented amyotrophic lateral sclerosis patients.

This study aimed at estimating the prevalence of language impairment (LI) in a large, clinic-based cohort of non-demented amyotrophic lateral sclerosis (ALS) patients and assessing its underpinnings at motor and non-motor levels. Non-demented ALS patients (N=348) underwent the Edinburgh Cognitive and Behavioural ALS Screen (ECAS), as well as an assessment of behavioural/psychiatric and motor-functional features. The prevalence of LI was estimated based on the proportion of patients showing a performance below the age- and education-adjusted cut-off on the ECAS-Language. Multiple regression models were run to assess the determinants of language functioning and impairment. The prevalence of LI was 22.7%. 46.6% of the variance of ECAS-Language scores remained unexplained, with only the ECAS-Executive positively predicting them (p < 0.001; η2 =0.07). Similarly, only a lower score on the ECAS-Executive predicted a higher probability of a below cut-off ECAS-Language performance (p < 0.001). Spelling and Naming tasks were the major drivers of ECAS-Language performance. This study suggests that, in non-demented ALS patients, LI occurs in ≈23% of cases, is significantly driven by executive dysfunction but, at the same time, partially independent of it and is not associated with other motor or non-motor features.

Verbal Reasoning Impairment in Parkinson's Disease.

The aim of this study was to assess verbal reasoning (VR) functioning in patients with Parkinson's disease (PD) and healthy controls (HCs). The non-demented PD patients and HCs matched by age and global cognition were enrolled in this study. VR was assessed with the verbal reasoning test (VRT), total score, and subsets. Eighty-seven PD patients (51 men; mean age 63.8 ± 7.9 years) and 87 HCs (46 men; mean age 63.7 ± 8.0 years) were enrolled. At univariate analysis, PD patients presented a significantly lower score in the VRT subset classification (12.3 ± 2.1) than HCs (12.9 ± 1.7) with an odds ratio (OR) of 0.8 (95% confidence interval [CI] 0.70-0.98; p = 0.003). The strength of association was also confirmed at multivariate analysis (OR = 0.8, 95% CI 0.70-0.98; p = 0.003). Moreover, in PD patients, a statistically significant positive correlation was found between VRT-classification and MoCA scores (r = 0.330; p = 0.002). PD patients presented lower VR performance than HCs.

Diagnostic properties of the Italian ECAS Carer Interview (ECAS-CI)

BackgroundThis study aimed at providing diagnostic properties and normative cut-offs for the Italian ECAS Carer Interview (ECAS-CI).MaterialsN = 292 non-demented ALS patients and N = 107 healthy controls (HCs) underwent the ECAS-CI and the Frontal Behavioural Inventory (FBI). Two ECAS-CI measures were addressed: (1) the number of symptoms (NoS; range = 0–13) and (2) that of individual symptom clusters (SC; range = 0–6). Diagnostics were explored against an FBI score ≥ than the 95th percentile of the patients’ distribution.ResultsBoth the NoS and SC discriminated patient from HCs. High accuracy, sensitivity, and specificity were detected for both the NoS and SC; however, at variance with SC, the NoS showed better post-test features and did not overestimate the occurrence of behavioural changes. The ECAS-CI converged with the FBI and diverged from the cognitive section of the ECAS.DiscussionThe ECAS-CI is a suitable screener for behavioural changes in ALS patients, with the NoS being its best outcome measure (cut-off: ≥ 3).

From pleasure to punding: Distinct patterns of anhedonia and impulsivity linked to motivational disturbances in Parkinson disease

Introduction Apathy and impulse control disorders (ICD) are common comorbid motivational syndromes in Parkinson disease (PD). This study aimed to determine if patients with these motivational disturbances exhibit different patterns of anhedonia and trait impulsivity. Methods Sixty-four non-demented patients with PD completed questionnaires assessing apathy and ICD symptoms, which were used to classify participants into one of the following groups: apathy only, ICD only, both, and neither. Participants also completed multidimensional measures of anhedonia and trait impulsivity, which were compared across groups defined by motivational status. Results Individuals with both apathy and ICD had significantly greater symptoms of positive and negative urgency than all other groups and had significantly greater consummatory anhedonia and lack of premeditation and perseverance than those with ICD only and neither. Patients with apathy only also reported significantly greater anticipatory anhedonia than those with ICD only and the neither group. There were no significant between-group differences in sensation seeking. Conclusion Distinct patterns of impulsivity and anhedonia characterize unique behavioral phenotypes of motivational disturbances in PD and may reflect important differences in the underlying neurobiological mechanisms. Clinicians should be aware that motivational disturbances may be more severe in cases where apathy co-occurs with one or more ICD. HIGHLIGHTS Highlights are mandatory for all submissions except letters. They consist of a short collection of bullet points that convey the core findings of the article and should be submitted in a separate file in the online submission system. Please use “Highlights” in the file name and include 3–5 bullet points (maximum 85 characters, including spaces, per bullet point). See https://www.elsevier.com/highlights for examples.

Regional cortical hypoperfusion and atrophy correlate with striatal dopaminergic loss in Parkinson's disease: a study using arterial spin labeling MR perfusion.

To investigate the relationship of the striatal dopamine transporter density to changes in the gray matter (GM) volume and cerebral perfusion in patients with Parkinson's disease (PD). We evaluated the regional cerebral blood flow (CBF) and GM volume, concurrently measured using arterial spin labeling and T1-weighted magnetic resonance imaging, respectively, as well as the striatal specific binding ratio (SBR) in 123I-N-ω-fluoropropyl-2β-carboxymethoxy-3β-(4-iodophenyl)nortropane (123I-FP-CIT) single-photon emission computed tomography in 30 non-demented patients with PD (15 men and 15 women; mean age, 67.2 ± 8.8years; mean Hoehn-Yahr stage, 2.2 ± 0.9). Voxel-wise regression analyses using statistical parametric mapping (SPM) were performed to explore the brain regions that showed correlations of the striatal SBR to the GM volume and CBF, respectively, with a height threshold of p < 0.0005 at the voxel level and p < 0.05 family-wise error-corrected at the cluster level. SPM analysis showed a significant positive correlation between the SBR and GM volume in the inferior frontal gyrus (IFG). Whereas, a positive correlation between the SBR and CBF was widely found in the frontotemporal and parietotemporal regions, including the IFG. Notably, the opercular part of the IFG showed significant correlations in both SPM analyses of the GM volume (r2 = 0.90, p < 0.0001) and CBF (r2 = 0.88, p < 0.0001). The voxel-wise analyses revealed the brain regions, mainly the IFG, that showed hypoperfusion and atrophy related to dopaminergic loss, which suggests that the progression of dopaminergic neurodegeneration leads to regional cortical dysfunction in PD.

Validity and diagnostics of the Reading the Mind in the Eyes Test (RMET) in non-demented amyotrophic lateral sclerosis (ALS) patients.

The aim of this study was to explore the construct validity and diagnostic properties of the Reading the Mind in the Eyes Test (RMET) in non-demented patients with amyotrophic lateral sclerosis (ALS). A total of 61 consecutive patients and 50 healthy controls (HCs) were administered the 36-item RMET. Additionally, patients underwent a comprehensive assessment of social cognition via the Story-Based Empathy Task (SET), which encompasses three subtests targeting Causal Inference, Emotion Attribution (SET-EA), and Intention Attribution (SET-IA), as well as global cognitive [the Edinburgh Cognitive and Behavioral ALS Screen (ECAS)] and behavioral screening [the Frontal Behavioral Inventory (FBI); the Dimensional Apathy Scale (DAS); the Beck Depression Inventory (BDI); and the State and Trait Anxiety Inventory-Y]. The construct validity of the RMET was tested by regressing it within a stepwise model that encompassed as predictors the abovementioned cognitive and behavioral measures, covarying for demographic and motor confounders. Receiver-operating characteristics (ROC) analyses allowed exploring intrinsic and post-test properties of the RMET both in discriminating patients from HCs and in identifying patients with a defective SET-EA performance. The RMET was solely predicted by the SET-EA (p = 0.003) and SET-IA (p = 0.005). RMET scores showed high accuracy both in discriminating patients from HCs (AUC = 0.81) and in identifying patients with a defective SET-EA score (AUC = 0.82), with adequate-to-optimal both intrinsic and post-test properties. The RMET is a convergently and divergently valid measure of affective social cognition in non-demented ALS patients, also featuring optimal intrinsic and post-test diagnostic properties in both case-control and case-finding scenarios.

Whole-transcriptome sequencing data reveals a disparate cognitive and immune signature in COVID-19 patients with and without dementia.

The coronavirus disease 2019 (COVID‐19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has caused more than 6.3 million deaths worldwide. Recent evidence has indicated that elderly people with dementia are particularly vulnerable to COVID‐19 and severe disease outcomes. However, its molecular mechanism remains largely unknown. Here, we retrieved frontal cortex samples of COVID‐19 patients from the Gene Expression Omnibus (GEO) database and performed a systematic transcriptomic analysis to compare COVID‐19 patients and controls with or without dementia. In nondemented patients, SARS‐CoV‐2 infection obviously activated T helper type 2 (Th2) cell‐mediated humoral immunity and reduced the pathogenesis of dementia‐related Alzheimer's disease and Parkinson's disease. In demented patients, conversely, SARS‐CoV‐2 infection significantly increased Th1 cell‐mediated cellular immunity and exacerbated the progression of dementia‐related diseases. We further analyzed the molecular characteristics of COVID‐19 patients with and without dementia. Compared with nondemented COVID‐19 patients, demented COVID‐19 patients showed decreased enrichment scores of Calcium signaling pathway, Neuroactive ligand‐receptor interaction, ABC transporters and Peroxisome, and increased enrichment scores of Olfactory transduction and Regulation of autophagy. The ratio of Th1/Th2 cells was significantly increased from 1.17 in nondemented COVID‐19 patients to 33.32 in demented COVID‐19 patients. Taken together, our findings provide transcriptomic evidence that COVID‐19 has distinct influences on cognitive function and immune response in patients with and without dementia.This article is protected by copyright. All rights reserved.

Identification of cholinergic centro-cingulate topography as main contributor to cognitive functioning in Parkinson's disease: Results from a data-driven approach.

Degeneration of the cholinergic system plays an important role in cognitive impairment in Parkinson's disease (PD). Positron emission tomography (PET) imaging using the presynaptic vesicular acetylcholine transporter (VAChT) tracer [18F]Fluoroethoxybenzovesamicol ([18F]FEOBV) allows for regional assessment of cholinergic innervation. The purpose of this study was to perform a data-driven analysis to identify co-varying cholinergic regions and to evaluate the relationship of these with cognitive functioning in PD. A total of 87 non-demented PD patients (77% male, mean age 67.9 ± 7.6 years, disease duration 5.8 ± 4.6 years) and 27 healthy control (HC) subjects underwent [18F]FEOBV brain PET imaging and neuropsychological assessment. A volume-of-interest based factor analysis was performed for both groups to identify cholinergic principal components (PCs). Seven main PCs were identified for the PD group: (1) bilateral posterior cortex, (2) bilateral subcortical, (3) bilateral centro-cingulate, (4) bilateral frontal, (5) right-sided fronto-temporal, (6) cerebellum, and (7) predominantly left sided temporal regions. A complementary principal component analysis (PCA) analysis in the control group showed substantially different cholinergic covarying patterns. A multivariate linear regression analyses demonstrated PC3, PC5, and PC7, together with motor impairment score, as significant predictors for cognitive functioning in PD. PC3 showed most robust correlations with cognitive functioning (p < 0.001). A data-driven approach identified covarying regions in the bilateral peri-central and cingulum cortex as a key determinant of cognitive impairment in PD. Cholinergic vulnerability of the centro-cingulate network appears to be disease-specific for PD rather than being age-related. The cholinergic system may be an important contributor to regional and large scale neural networks involved in cognitive functioning.

Feasibility and diagnostics of the Frontal Assessment Battery (FAB) in amyotrophic lateral sclerosis

BackgroundThe present study aimed at evaluating the diagnostic properties of the Frontal Assessment Battery (FAB) in non-demented ALS patients by addressing the Edinburgh Cognitive Behavioural ALS Screen (ECAS) as the gold standard, as well as by examining the association between its administrability and scores with motor-functional measures.MaterialsN = 348 consecutive patients were administered the ECAS and FAB. Disease severity (ALSFRS-R), duration, progression rate (ΔFS), and stages (via King’s and Milano-Torino systems) were considered. Administrability rates and prevalence of below-cut-off FAB scores were compared across clinical stages; regression models allowed to test whether, net of the ECAS-Total, motor features predicted the probability of the FAB not being administrable and of a defective FAB score. Intrinsic and post-test diagnostics were explored against a combined defective ECAS-Executive and ECAS-Fluency scores.Results85.3% of patients managed to complete the FAB. FAB administrability rates decreased with advanced clinical stages, whereas the prevalence of below-cut-off FAB scores did not. The probability of the FAB not being administrable was predicted only by lower ALSFRS-R-bulbar and ALSFRS-R-upper-limb scores; no motor features, but the ECAS-Total, predicted a below-cut-off performance on the FAB. Raw and adjusted FAB scores showed high accuracy (AUC = .85 and .81, respectively) and good intrinsic and post-test properties.DiscussionThe FAB is featured by optimal diagnostics for detecting executive deficits in ALS, provided that it can be administered according to its original, standardized procedure, and thus that patients have sufficiently spared motor abilities to complete the test.

Diagnostics and clinical usability of the Montreal Cognitive Assessment (MoCA) in amyotrophic lateral sclerosis.

BackgroundThe present study aimed at (1) assessing the diagnostic properties of the Montreal Cognitive Assessment (MoCA) in non-demented ALS patients and at (2) exploring the MoCA administrability according to motor-functional status.MaterialsN = 348 patients were administered the MoCA and Edinburgh Cognitive and Behavioural ALS Screen (ECAS). Administrability rates and prevalence of defective MoCA scores were compared across King’s and Milano-Torino clinical stages. Regression models were run to test whether the non-administrability of the MoCA and a defective score on it were predicted, net of the ECAS-Total, by disease duration, ALS Functional Rating Scale-Revised (ALSFRS-R) and progression rate, computed as (48: ALSFRS-R)/disease duration. Intrinsic and post-test diagnostics were tested against a below-cut-off ECAS-total score.ResultsThe 79.9% of patients successfully underwent the MoCA, whose administrability rates decreased with advanced clinical stages, at variance with its defective score prevalence. The probability of the FAB not being administrable was predicted only by lower ALSFRS-R-bulbar and-upper-limb scores; no motor features, but the ECAS-Total, predicted a defective MoCA performance. The MoCA showed high accuracy (AUC = 0.82) and good intrinsic and post-test properties—being slightly more specific than sensitive.DiscussionIn non-demented ALS patients, the MoCA is featured by optimal diagnostics as a screener for cognitive impairment, especially for ruling-out its occurrence, as long as patients are in the early stages of the disease and have sufficiently spared bulbar and upper-limb functions.

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.

The role of attentional control over interference in minor hallucinations in Parkinson’s disease

BackgroundMinor hallucinations in Parkinson's disease are associated with connectivity changes in attentional networks and increased risk of structured hallucinations. However, the clinical translation of these abnormalities in attention processes is not well-defined, and commonly used neuropsychological tests are not able to detect significant deficits in Parkinson's disease patients with isolated minor hallucinations. ObjectivesTo analyze the behavioral and electrophysiological correlates of minor hallucinations in Parkinson's disease during an attentional task assessing response inhibition and interference control. MethodsFifty-five non-demented Parkinson's disease patients with (PD-mH; n = 27) and without minor hallucinations (PD-NH; n = 28) were included in the analysis. An Ericksen flanker task was performed to compare the effect of presenting congruent and incongruent stimuli on accuracy, reaction times and stimulus-locked event-related potentials morphology. ResultsAlthough both groups showed equivalent performance in a standard neuropsychological assessment, in the flanker task accuracy rates were lower in the PD-mH group in incongruent trials (p = 0.005). In the event-related potentials, PD-mH patients showed increased amplitude of the N2 at Fz [t(53); p < 0.05] and decreased amplitude of the P300 at Pz [t(53); p < 0.05] for the incongruent trials. ConclusionsParkinson's disease patients with isolated minor hallucinations were more susceptible to interference mediated by irrelevant stimuli and had less cognitive control for suppressing these interferences. The failure of these systems could precipitate the intrusion and overrepresentation of peripheral irrelevant stimuli perceived as minor hallucinations. The Ericksen flanker task could be used as a sensitive clinical marker of the attentional defects leading to hallucinations in Parkinson's disease.

Iron quantitative analysis of motor combined with bulbar region in M1 cortex may improve diagnosis performance in ALS.

To explore whether the combined analysis of motor and bulbar region of M1 on susceptibility-weighted imaging (SWI) can be a valid biomarker for amyotrophic lateral sclerosis (ALS). Thirty-two non-demented ALS patients and 35 age- and gender-matched healthy controls (HC) were retrospectively recruited. SWI and 3D-T1-MPRAGE images were obtained from all individuals using a 3.0-T MRI scan. The bilateral posterior band of M1 was manually delineated by three neuroradiologists on phase images and subdivided into the motor and bulbar regions. We compared the phase values in two groups and performed a stratification analysis (ALSFRS-R score, duration, disease progression rate, and onset). Receiver operating characteristic (ROC) curves were also constructed. ALS group showed significantly increased phase values in M1 and the two subregions than the HC group, on the all and elderly level (p < 0.001, respectively). On all-age level comparison, negative correlations were found between phase values of M1 and clinical score and duration (p < 0.05, respectively). Similar associations were found in the motor region (p < 0.05, respectively). On both the total (p < 0.01) and elderly (p < 0.05) levels, there were positive relationships between disease progression rate and M1 phase values. In comparing ROC curves, the entire M1 showed the best diagnostic performance. Combining motor and bulbar analyses as an integral M1 region on SWI can improve ALS diagnosis performance, especially in the elderly. The phase value could be a valuable biomarker for ALS evaluation. • Integrated analysis of the motor and bulbar as an entire M1 region on SWI can improve the diagnosis performance in ALS. • Quantitative analysis of iron deposition by SWI measurement helps the clinical evaluation, especially for the elderly patients. • Phase value, when combined with the disease progression rate, could be a valuable biomarker for ALS.

Feasibility and usability of a non-immersive virtual reality tele-cognitive app in cognitive rehabilitation of patients affected by Parkinson's disease.

Cognitive impairment is one of the most common non-motor features of Parkinson's disease (PD). The aim of the present study was to evaluate the feasibility and acceptability/usability of a protocol using a non-immersive virtual reality tele-cognitive app, performed remotely in a sample of Italian patients with PD. Non-demented patients with mild PD were included in the study. Patients performed the cognitive rehabilitation in a remote way, at home (three training sessions lasting 20 min/week for 6 weeks) using the NeuroNation app, downloaded for free on the patients' smartphones. The usability and feasibility of the tele-cognitive rehabilitation program were assessed with the System Usability Scale (SUS) and the Goal Attainment Scaling (GAS). Sixteen patients (9 men and 7 women; mean age 58.4 ± 8.3 years; mean disease duration 4.6 ± 2.1 years) were included in the study. At the end of the study, the mean SUS was 83.4 ± 11.5. The GAS score recorded at the end of the study (65.6 ± 4.2) was significantly higher than at baseline (38.5 ± 2.4; P-value <0.001). In our sample, good feasibility and usability were observed for a 6-week cognitive rehabilitation protocol based on the non-immersive virtual reality tele-cognitive app NeuroNation. Our data support the usefulness of cognitive rehabilitation performed in a remote way in PD patients.

YKL-40 changes are not detected in post-mortem brain of patients with Alzheimer’s disease and frontotemporal lobar degeneration

BackgroundYKL-40 (Chitinase 3-like I) is increased in CSF of Alzheimer’s disease (AD) and frontotemporal lobar degeneration (FTLD) patients and is therefore considered a potential neuroinflammatory biomarker. Whether changed YKL-40 levels in the CSF reflect dysregulation of YKL-40 in the brain is not completely understood yet. We aimed to extensively analyze YKL-40 levels in the brain of AD and different FTLD pathological subtypes. The direct relationship between YKL-40 levels in post-mortem brain and ante-mortem CSF was examined in a small set of paired brain-CSF samples.MethodYKL-40 was analyzed in post-mortem temporal and frontal cortex of non-demented controls and patients with AD and FTLD (including FTLD-Tau and FTLD-TDP) pathology by immunohistochemistry (temporal cortex: 51 controls and 56 AD and frontal cortex: 7 controls and 24 FTLD patients), western blot (frontal cortex: 14 controls, 5 AD and 67 FTLD patients), or ELISA (temporal cortex: 11 controls and 7 AD and frontal cortex: 14 controls, 5 AD and 67 FTLD patients). YKL-40 levels were also measured in paired post-mortem brain and ante-mortem CSF samples from dementia patients (n = 9, time-interval collection: 1.4 years) by ELISA.ResultsWe observed that YKL-40 post-mortem brain levels were similar between AD, FTLD, and controls as shown by immunohistochemistry, western blot, and ELISA. Interestingly, strong YKL-40 immunoreactivity was observed in AD cases with cerebral amyloid angiopathy (CAA; n = 6). In paired CSF-brain samples, YKL-40 concentration was 8-times higher in CSF compared to brain.ConclusionOur data suggest that CSF YKL-40 changes may not reflect YKL-40 changes within AD and FTLD pathological brain areas. The YKL-40 reactivity associated with classical CAA hallmarks indicates a possible relationship between YKL-40, neuroinflammation, and vascular pathology.