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INTRODUCTION: Mild cognitive impairment is a common feature of Parkinson's disease (PD-MCI), even at the earliest disease stages. Growing evidence supports the instability of PD-MCI over time, without a consistent linear evolution to dementia, and in some patients, the potential of reversion to normal cognition. However, which features are associated with reversion from PD-MCI to normal cognition in early PD-MCI are not fully known. METHODS: In our longitudinal study of early drug naïve PD patients, 65 of 134 (48 %) patients had PD-MCI at baseline. Study participants underwent comprehensive assessments at baseline and 1-year follow-up. Sixteen (24.6 %) patients with PD-MCI reverted to normal cognition (Reverters), and 49 (75.4 %) had persistent PD-MCI (Non-Reverters) after 1-year follow-up. We performed single- and multiple-variable logistic regression analyses to identify baseline variables predicting reversion of PD-MCI to normal cognition after 1-year. We also compared brain morphometric measures (cortical thickness and volumes) at baseline between the PD-MCI Reverters and Non-Reverters. RESULTS: Higher educational level and better performance on measures of attention and memory at baseline predicted the reversion to normal cognition at 1-year follow-up. Reverters had greater cortical thickness in the left inferior temporal gyrus than Non-Reverters. CONCLUSIONS: Our results show PD-MCI with a higher chance of reverting to normal cognition over time have a higher educational level, better frontotemporal-related cognitive function, and increased thickness of the inferior temporal lobe gyrus. These findings may potentially help researchers to select the candidates for clinical trials focusing on the treatment of cognitive impairment in the early stages of PD.
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PURPOSE OF THE REVIEW: In this review, we attempt to summarize the most updated studies that applied resting-state functional magnetic resonance imaging (rs-fMRI) in the field of Parkinsonisms and related dementia. RECENT FINDINGS: Over the past decades, increasing interest has emerged on investigating the presence and pathophysiology of cognitive symptoms in Parkinsonisms and their possible role as predictive biomarkers of neurodegenerative brain processes. In recent years, evidence has been provided, applying mainly three methodological approaches (i.e. seed-based, network-based and graph-analysis) on rs-fMRI data, with promising results. Neural correlates of cognitive impairment and dementia have been detected in patients with Parkinsonisms along the diseases course. Interestingly, early functional connectivity signatures were proposed to track and predict future progression of neurodegenerative processes. However, longitudinal studies are still sparce and further investigations are needed to overcome this knowledge gap.
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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.
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BACKGROUND: In this study, we aimed at investigating the possible association of urinary symptoms with whole-brain MRI resting-state functional connectivity (FC) alterations from distinct striatal subregions in a large cohort of early PD patients. METHODS: Seventy-nine drug-naive PD patients (45 PD-urinary+/34 PD-urinary-) and 38 healthy controls (HCs) were consecutively enrolled. Presence/absence of urinary symptoms were assessed by means of the Nonmotor Symptom Scale - domain 7. Using an a priori connectivity-based domain-specific parcellation, we defined three ROIs (per each hemisphere) for different striatal functional subregions (sensorimotor, limbic and cognitive) from which seed-based FC voxel-wise analyses were conducted over the whole brain. RESULTS: Compared to PD-urinary-, PD-urinary+ patients showed increased FC between striatal regions and motor and premotor/supplementary motor areas as well as insula/anterior dorsolateral PFC. Compared to HC, PD-urinary+ patients presented decreased FC between striatal regions and parietal, insular and cingulate cortices. CONCLUSIONS: Our findings revealed a specific pattern of striatal FC alteration in PD patients with urinary symptoms, potentially associated to altered stimuli perception and sensorimotor integration even in the early stages. These results may potentially help clinicians to design more effective and tailored rehabilitation and neuromodulation protocols for PD patients.
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Corpo Estriado , Imageamento por Ressonância Magnética , Doença de Parkinson , Humanos , Doença de Parkinson/fisiopatologia , Doença de Parkinson/diagnóstico por imagem , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Corpo Estriado/diagnóstico por imagem , Corpo Estriado/fisiopatologia , Vias Neurais/fisiopatologia , Vias Neurais/diagnóstico por imagemRESUMO
BACKGROUND: Subjective cognitive complaints (SCCs) in Parkinson's disease (PD) are reported frequently, but their prevalence and association with changes on objective testing are not fully known. OBJECTIVE: We aimed to determine the prevalence, clinical correlates, and predictive value of SCCs in PD. METHODS: We conducted a systematic review and meta-analysis. From 204 abstracts, we selected 31 studies (n = 3441 patients), and from these, identified the prevalence, clinical features, associations with neuropsychiatric symptoms, and predictive values of SCCs in PD. RESULTS: The meta-analysis showed an SCC prevalence of 36%. This prevalence, however, was significantly moderated by study heterogeneity regarding female sex, disease severity, levodopa equivalent daily dosage, exclusion from the overall sample of patients with objective cognitive impairment, and measurement instrument. SCC prevalence did not differ between de novo and treated PD patients. SCCs were weakly and negligibly associated with cognitive changes on objective testing in cross-sectional studies. However, in cognitively healthy patients, SCCs had a risk ratio of 2.71 for later cognitive decline over a mean follow-up of 3.16 years. Moreover, SCCs were moderately related to co-occurring symptoms of depression, anxiety, or apathy and were more strongly related to these neuropsychiatric symptoms than objective cognitive functioning. CONCLUSION: Our analyses suggest that SCCs in patients with and without objective cognitive impairment are frequent, occurring in more than one third of PD patients. Establishing uniform measurement instruments for identifying PD-related SCCs is critical to understand their implications. Even in cases lacking evidence of objective cognitive impairment and where SCCs might reflect underlying neuropsychiatric symptoms, the possibility of later cognitive deterioration should not be excluded. Therefore, SCCs in PD patients warrant close monitoring for opportunities for targeted and effective interventions. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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Transtornos Cognitivos , Disfunção Cognitiva , Doença de Parkinson , Humanos , Feminino , Doença de Parkinson/complicações , Doença de Parkinson/epidemiologia , Doença de Parkinson/psicologia , Estudos Transversais , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/epidemiologia , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/complicações , CogniçãoRESUMO
OBJECTIVE: The capacity to take another person's visual perspective is pivotal for solving mindreading tests, such as Theory of Mind (ToM) tasks, but most of them heavily rely on domain-general abilities (e.g., language, executive functions). Here we present a novel battery of visual perspective-taking tests for child neuropsychological assessment, the Perspective Battery (PERBAT), which poses a limited load on domain-general abilities. METHODS: The battery includes four tests: i) Block Building; ii) Hide and Seek; iii) Deceptive Figures; iv) Double-Sided Shelf. We administered the PERBAT to 126 typically developing preschoolers (65 males; 3-6-year-old); the participants also performed classical tests of social cognition, language, and nonverbal abstract reasoning. RESULTS: The scores of all the PERBAT tests were significantly and positively related with age and scores of the classical social cognition tests, but not with scores of the language and nonverbal abstract reasoning tests. CONCLUSIONS: The PERBAT could represent a useful neuropsychological tool providing a comprehensive assessment of visual perspective-taking skills in preschool children. Future investigation is needed to examine the validity of the PERBAT with neurotypical samples across countries, race, ethnicity, and language as well as with clinical populations. Longitudinal studies are also encouraged to examine whether early visual perspective-taking weaknesses are associated with later development of mindreading skills.
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Função Executiva , Teoria da Mente , Masculino , Pré-Escolar , Humanos , Criança , Testes Neuropsicológicos , Idioma , CogniçãoRESUMO
BACKGROUND: Treatment-related motor complications may develop progressively over the course of Parkinson's disease (PD). OBJECTIVE: We investigated intrinsic brain networks functional connectivity (FC) at baseline in a cohort of early PD patients which successively developed treatment-related motor complications over 4 years. METHODS: Baseline MRI images of 88 drug-naïve PD patients and 20 healthy controls were analyzed. After the baseline assessments, all PD patients were prescribed with dopaminergic treatment and yearly clinically re-assessed. At the 4-year follow-up, 36 patients have developed treatment-related motor complications (PD-Compl) whereas 52 had not (PD-no-Compl). Single-subject and group-level independent component analyses were used to investigate FC changes within the major large-scale resting-state networks at baseline. A multivariate Cox regression model was used to explore baseline predictors of treatment-related motor complications at 4-year follow-up. RESULTS: At baseline, an increased FC in the right middle frontal gyrus within the frontoparietal network as well as a decreased connectivity in the left cuneus within the default-mode network were detected in PD-Compl compared with PD-no-Compl. PD-Compl patients showed a preserved sensorimotor FC compared to controls. FC differences were found to be independent predictors of treatment-related motor complications over time. CONCLUSION: Our findings demonstrated that specific FC differences may characterize drug-naïve PD patients more prone to develop treatment-related complications. These findings may reflect the presence of an intrinsic vulnerability across frontal and prefrontal circuits, which may be potentially targeted as a future biomarker in clinical trials.
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Doença de Parkinson , Humanos , Doença de Parkinson/complicações , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/tratamento farmacológico , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico/métodos , Dopamina , Imageamento por Ressonância Magnética/métodosRESUMO
Background: Heterozygous mutations in the GBA gene, encoding the lysosomal enzyme ß-glucocerebrosidase (GCase), are the most frequent genetic risk factor for Parkinson's disease (PD). GBA-related PD (GBA-PD) patients have higher risk of dementia and reduced survival than non-carriers. Preclinical studies and one open-label trial in humans demonstrated that the chaperone ambroxol (ABX) increases GCase levels and modulates α-synuclein levels in the blood and cerebrospinal fluid (CSF). Methods and analysis: In this multicentre, double-blind, placebo-controlled, phase II clinical trial, we randomise patients with GBA-PD in a 1:1 ratio to either oral ABX 1.2 g/day or placebo. The duration of treatment is 52 weeks. Each participant is assessed at baseline and weeks 12, 26, 38, 52 and 78. Changes in the Montreal Cognitive Assessment score and the frequency of mild cognitive impairment and dementia between baseline and weeks 52 are the primary outcome measures. Secondary outcome measures include changes in validated scales/questionnaires assessing motor and non-motor symptoms. Neuroimaging features and CSF neurodegeneration markers are used as surrogate markers of disease progression. GCase activity, ABX and α-synuclein levels are also analysed in blood and CSF. A repeated-measures analysis of variance will be used for elaborating results. The primary analysis will be by intention to treat. Ethics and dissemination: The study and protocols have been approved by the ethics committee of centres. The study is conducted according to good clinical practice and the Declaration of Helsinki. The trial findings will be published in peer-reviewed journals and presented at conferences. Trial registration numbers: NCT05287503, EudraCT 2021-004565-13.
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INTRODUCTION: Fatigue is defined as a symptom of exhaustion unexplained by drug effects or psychiatric disorders and comprises two main components (i.e., central or "mental" and peripheral or "physical" components), both influencing global disability in amyotrophic lateral sclerosis (ALS). We aim at investigating the clinical correlations between "physical" and "mental" components of fatigue, measured by the Multidimensional Fatigue Inventory scale, and motor and cognitive/behavioral disability in a large sample of patients with ALS. We also investigated the correlations between these measures of fatigue and resting-state functional connectivity of brain functional magnetic resonance imaging (RS-fMRI) large-scale networks in a subset of patients. METHODS: One hundred and thirty ALS patients were assessed for motor disability, cognitive and behavioral dysfunctions, fatigue, anxiety, apathy, and daytime sleepiness. Moreover, the collected clinical parameters were correlated with RS-fMRI functional connectivity changes in the large-scale brain networks of 30 ALS patients who underwent MRI. RESULTS: Multivariate correlation analysis revealed that "physical" fatigue was related to anxiety and respiratory dysfunction, while "mental" fatigue was related to memory impairment and apathy. Moreover, the mental fatigue score was directly related to functional connectivity in the right and left insula (within the salience network), and inversely related to functional connectivity in the left middle temporal gyrus (within the default mode network). CONCLUSIONS: Although the "physical" component of fatigue may be influenced by the disease itself, in ALS the "mental" component of fatigue correlates with cognitive and behavioral impairment, as well as with alterations of functional connectivity in extra-motor networks.
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Esclerose Lateral Amiotrófica , Pessoas com Deficiência , Transtornos Motores , Humanos , Esclerose Lateral Amiotrófica/complicações , Esclerose Lateral Amiotrófica/diagnóstico por imagem , Encéfalo , Imageamento por Ressonância Magnética/métodos , Fadiga Mental/diagnóstico por imagem , Fadiga Mental/etiologia , CogniçãoRESUMO
BACKGROUND: Memory deficits in mild cognitive impairment related to Parkinson's disease (PD-MCI) are quite heterogeneous, and there is no general agreement on their genesis. OBJECTIVES: To define memory phenotypes in de novo PD-MCI and their associations with motor and non-motor features and patients' quality of life. METHODS: From a sample of 183 early de novo patients with PD, cluster analysis was applied to neuropsychological measures of memory function of 82 patients with PD-MCI (44.8%). The remaining patients free of cognitive impairment were considered as a comparison group (n = 101). Cognitive measures and structural magnetic resonance imaging-based neural correlates of memory function were used to substantiate the results. RESULTS: A three-cluster model produced the best solution. Cluster A (65.85%) included memory unimpaired patients; Cluster B (23.17%) included patients with mild episodic memory disorder related to a "prefrontal executive-dependent phenotype"; Cluster C (10.97%) included patients with severe episodic memory disorder related to a "hybrid phenotype," where hippocampal-dependent deficits co-occurred with prefrontal executive-dependent memory dysfunctions. Cognitive and brain structural imaging correlates substantiated the findings. The three phenotypes did not differ in terms of motor and non-motor features, but the attention/executive deficits progressively increased from Cluster A, through Cluster B, to Cluster C. This last cluster had worse quality of life compared to others. CONCLUSIONS: Our results demonstrated the memory heterogeneity of de novo PD-MCI, suggesting existence of three distinct memory-related phenotypes. Identification of such phenotypes can be fruitful in understanding the pathophysiological mechanisms underlying PD-MCI and its subtypes and in guiding appropriate treatments. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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Disfunção Cognitiva , Doença de Parkinson , Humanos , Doença de Parkinson/complicações , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/patologia , Qualidade de Vida , Testes Neuropsicológicos , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/complicações , Transtornos da Memória , Fenótipo , Função ExecutivaRESUMO
INTRODUCTION: Migraine is a leading cause of years lived with disability and preventive strategies represent a mainstay to reduce health-related disability and improve quality of life of migraine patients. Until a few years ago, migraine prevention was based on drugs developed for other clinical indications and relocated in the migraine therapeutic armamentarium, characterized by unfavorable tolerability profiles. The advent of monoclonal antibodies against Calcitonin Gene-Related Peptide (CGRP) and gepants, CGRP receptor antagonists, has been a turning point in migraine prevention owing to advantageous efficacy, safety and tolerability profiles.Nevertheless, while in an ideal scenario a drug characterized by significant greater efficacy and tolerability compared to existing therapeutic strategies should be adopted as a first-line treatment, cost-effectiveness analyses available for monoclonal antibodies against CGRP pathway tend to limit their administration to more severe migraine phenotypes. AREAS COVERED: The present narrative review aims to provide a critical appraisal of phase II and III CGRP-mAbs and gepants trials to analyze their use in clinical practice. EXPERT OPINION: Despite monoclonal antibodies against CGRP pathway and gepants can be undoubtedly considered top-of-the-range treatments, there are still issues deserving to be addressed in the coming years as the risk of off-target effects as well as their economic sustainability based on the considerable migraine burden.
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Peptídeo Relacionado com Gene de Calcitonina , Transtornos de Enxaqueca , Humanos , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Antagonistas do Receptor do Peptídeo Relacionado ao Gene de Calcitonina/farmacologia , Antagonistas do Receptor do Peptídeo Relacionado ao Gene de Calcitonina/uso terapêutico , Anticorpos Monoclonais/efeitos adversos , Preparações Farmacêuticas , Qualidade de Vida , Transtornos de Enxaqueca/tratamento farmacológico , Transtornos de Enxaqueca/prevenção & controleRESUMO
The structural connectivity from the primary olfactory cortex to the main secondary olfactory areas was previously reported as relatively increased in the medial orbitofrontal cortex in a cohort of 27 recently SARS-CoV-2-infected (COV+) subjects, of which 23/27 had clinically confirmed olfactory loss, compared to 18 control (COV-) normosmic subjects, who were not previously infected. To complement this finding, here we report the outcome of an identical high angular resolution diffusion MRI analysis on follow-up data sets collected in 18/27 COV+ subjects (10 males, mean age ± SD: 38.7 ± 8.1 years) and 10/18 COV- subjects (5 males, mean age ± SD: 33.1 ± 3.6 years) from the previous samples who repeated both the olfactory functional assessment and the MRI examination after ~1 year. By comparing the newly derived subgroups, we observed that the increase in the structural connectivity index of the medial orbitofrontal cortex was not significant at follow-up, despite 10/18 COV+ subjects were still found hyposmic after ~1 year from SARS-CoV-2 infection. We concluded that the relative hyperconnectivity of the olfactory cortex to the medial orbitofrontal cortex could be, at least in some cases, an acute or reversible phenomenon linked to the recent SARS-CoV-2 infection with associated olfactory loss.
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COVID-19 , Masculino , Humanos , Seguimentos , SARS-CoV-2 , Encéfalo/diagnóstico por imagem , Lobo FrontalRESUMO
Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulation technique that is used against cognitive impairment in mild cognitive impairment (MCI) and Alzheimer's disease (AD). However, the neurobiological mechanisms underlying the rTMS therapeutic effects are still only partially investigated. Maladaptive plasticity, glial activation, and neuroinflammation, including metalloproteases (MMPs) activation, might represent new potential targets of the neurodegenerative process and progression from MCI to AD. In this study, we aimed to evaluate the effects of bilateral rTMS over the dorsolateral prefrontal cortex (DLPFC) on plasmatic levels of MMP1, -2, -9, and -10; MMPs-related tissue inhibitors TIMP1 and TIMP2; and cognitive performances in MCI patients. Patients received high-frequency (10 Hz) rTMS (MCI-TMS, n = 9) or sham stimulation (MCI-C, n = 9) daily for four weeks, and they were monitored for six months after TMS. The plasmatic levels of MMPs and TIMPs and the cognitive and behavioral scores, based on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Beck Depression Inventory II, Beck Anxiety Inventory, and Apathy Evaluation Scale, were assessed at baseline (T0) and after 1 month (T1) and 6 months (T2) since rTMS. In the MCI-TMS group, at T2, plasmatic levels of MMP1, -9, and -10 were reduced and paralleled by increased plasmatic levels of TIMP1 and TIMP2 and improvement of visuospatial performances. In conclusion, our findings suggest that targeting DLPFC by rTMS might result in the long-term modulation of the MMPs/TIMPs system in MCI patients and the neurobiological mechanisms associated with MCI progression to dementia.
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Doença de Alzheimer , Disfunção Cognitiva , Humanos , Estimulação Magnética Transcraniana/métodos , Metaloproteinase 1 da Matriz , Disfunção Cognitiva/psicologia , Doença de Alzheimer/terapia , Metaloproteinases da Matriz , Córtex Pré-FrontalRESUMO
BACKGROUND: Cluster headache is commonly reported to follow an annual pattern with a peak in the spring and a second peak in autumn. Patients with headache frequently use search engines, such as Google, to look for terms related to their disease, creating trend data that can be analyzed with Google Trends. Indeed, Google Trends has been used for surveillance studies and can provide indirect estimates of the burden of diseases and symptoms. The present cross-sectional study investigated the seasonality of searches for "cluster headache" in the northern and southern hemispheres using 10 years of Google Trends data. METHODS: The term "cluster headache" or its translation in the 10 most spoken languages in the world was searched on Google Trends to obtain relative search volumes (from 0 to 100), in order to compare variations in searches across periods. Twenty-eight countries were selected according to the following criteria: (1) a relative search volume of >40 for the term for cluster headache; and (2) a population of at least 5 million inhabitants. For statistical purposes, countries were grouped in relation to hemisphere (northern or southern). Relative search volumes were extracted from January 2012 to January 2022 and analyzed according to two subgroups based on meteorological seasons (summer and winter vs. spring and autumn). RESULTS: A seasonal trend for in searches for cluster headache was found worldwide exhibiting higher relative search volumes in spring and autumn compared with summer and winter (17 [0, 39] vs. 13 [0, 37]; p = 0.016). CONCLUSION: Higher search volumes for the term during the meteorological seasons of spring and autumn clearly reflect a circannual pattern of cluster headache occurrence, representing new evidence for its seasonality.
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Infodemiologia , Ferramenta de Busca , Humanos , Estudos Transversais , Estações do Ano , Cefaleia/epidemiologia , InternetRESUMO
Pseudobulbar affect (PBA), referring to exaggerated or inappropriate episodes of laughing and/or crying without an apparent motivating stimulus, has been mainly attributed to bilateral degeneration of corticobulbar tracts. We aimed at exploring brain functional connectivity (FC) correlates of PBA in patients with amyotrophic lateral sclerosis (ALS), the most common motor neuron disease, frequently associated with PBA. Resting state functional MRI (RS-fMRI) independent component (ICA) and seed-based analyses and voxel-based morphometry (VBM) whole-brain analysis were performed on 27 ALS patients (13 with PBA; 14 without PBA) and 26 healthy controls (HC), for investigating functional and structural abnormalities in ALS patients compared to HC and in patients with PBA compared to patients without PBA. Between-patient analysis revealed different FC patterns, especially regarding decreased FC in several areas of cognitive (default mode, frontoparietal, salience) and sensory-motor networks in patients with PBA compared to those without PBA. However, no significant differences were found in gray matter atrophy. Seed-based analysis showed increased FC between middle cerebellar peduncles and posterior cingulate cortex and decreased FC between middle cerebellar peduncles and left middle frontal gyrus in patients with PBA compared to patients without PBA. Our findings suggest that some alterations of fronto-tempo-parietal-cerebellar circuits could be related to PBA in ALS. In particular, the abnormal FC between cerebellum and posterior cingulate cortex and left middle frontal gyrus in patients with PBA compared to patients without PBA highlights a crucial role of the cerebellum in regulating emotion expression in patients with ALS.
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Esclerose Lateral Amiotrófica , Imageamento por Ressonância Magnética , Humanos , Encéfalo/diagnóstico por imagem , Substância Cinzenta/diagnóstico por imagem , Córtex CerebralRESUMO
Epidemiological studies have shown that Parkinson's disease (PD) patients with probable REM sleep behavior disorder (pRBD) present an increased risk of worse cognitive progression over the disease course. The aim of this study was to investigate, using resting-state functional MRI (RS-fMRI), the functional connectivity (FC) changes associated with the presence of pRBD in a cohort of newly diagnosed, drug-naive and cognitively unimpaired PD patients compared to healthy controls (HC). Fifty-six drug-naïve patients (25 PD-pRBD+ and 31 PD-pRBD-) and 23 HC underwent both RS-fMRI and clinical assessment. Single-subject and group-level independent component analysis was used to analyze intra- and inter-network FC differences within the major large-scale neurocognitive networks, namely the default mode (DMN), frontoparietal (FPN), salience (SN) and executive-control (ECN) networks. Widespread FC changes were found within the most relevant neurocognitive networks in PD patients compared to HC. Moreover, PD-pRBD+ patients showed abnormal intrinsic FC within the DMN, ECN and SN compared to PD-pRBD-. Finally, PD-pRBD+ patients showed functional decoupling between left and right FPN. In the present study, we revealed that FC changes within the most relevant neurocognitive networks are already detectable in early drug-naïve PD patients, even in the absence of clinical overt cognitive impairment. These changes are even more evident in PD patients with RBD, potentially leading to profound impairment in cognitive processing and cognitive/behavioral integration, as well as to fronto-striatal maladaptive compensatory mechanisms.
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Disfunção Cognitiva , Doença de Parkinson , Transtorno do Comportamento do Sono REM , Humanos , Mapeamento Encefálico , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/complicações , Imageamento por Ressonância Magnética , Doença de Parkinson/complicações , Doença de Parkinson/diagnóstico por imagem , Transtorno do Comportamento do Sono REM/diagnóstico por imagemRESUMO
The coronavirus disease 2019 (COVID-19) pandemic confined most of the population to homes worldwide, and then, a lot of amyotrophic lateral sclerosis (ALS) centers moved to telemedicine services to continue to assist both patients with ALS and their caregivers. This pilot, randomized, controlled study aimed to explore the potential role of psychological support interventions for family caregivers of patients with ALS through resilience-oriented sessions of group therapy during the COVID-19 pandemic. In total, 12 caregivers agreed to be remotely monitored by our center since March 2020 and underwent scales for global burden (i.e., Caregiver Burden Inventory, CBI), resilience (i.e., Connor Davidson Resilience Scale, CD-RISC), and perceived stress (i.e., Perceived Stress Scale, PSS) at two-time points (i.e., at pre-treatment assessment and after 9 months or at post-treatment assessment). They were randomized into two groups: the former group underwent resilience-oriented sessions of group therapy two times a month for 3 months, while the latter one was only remotely monitored. No significant differences were found in CBI, CD-RISC, and PSS during the 9-month observation period in the treated group compared with the control group, suggesting a trend toward stability of caregiver burden together with resilience and perceived stress scores in all the subjects monitored. The lack of differences in caregivers' burden, resilience, and perceived stress scores by comparing the two groups monitored during 9 months could be due to the co-occurrence of the COVID-19 pandemic with the stressful events related to caring for patients with ALS that might have hindered the detection of significant benefits from short-lasting psychological support.
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Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive neuromodulation technique that is increasingly used as a nonpharmacological intervention against cognitive impairment in Alzheimer's disease (AD) and other dementias. Although rTMS has been shown to modify cognitive performances and brain functional connectivity (FC) in many neurological and psychiatric diseases, there is still no evidence about the possible relationship between executive performances and resting-state brain FC following rTMS in patients with mild cognitive impairment (MCI). In this preliminary study, we aimed to evaluate the possible effects of rTMS of the bilateral dorsolateral prefrontal cortex (DLPFC) in 27 MCI patients randomly assigned to two groups: one group received high-frequency (10 Hz) rTMS (HF-rTMS) for four weeks (n = 11), and the other received sham stimulation (n = 16). Cognitive and psycho-behavior scores, based on the Repeatable Battery for the Assessment of Neuropsychological Status, Beck Depression Inventory-II, Beck Anxiety Inventory, Apathy Evaluation Scale, and brain FC, evaluated by independent component analysis of resting state functional MRI (RS-fMRI) networks, together with the assessment of regional atrophy measures, evaluated by whole-brain voxel-based morphometry (VBM), were measured at baseline, after five weeks, and six months after rTMS stimulation. Our results showed significantly increased semantic fluency (p = 0.026) and visuo-spatial (p = 0.014) performances and increased FC within the salience network (p ≤ 0.05, cluster-level corrected) at the short-term timepoint, and increased FC within the left fronto-parietal network (p ≤ 0.05, cluster-level corrected) at the long-term timepoint, in the treated group but not in the sham group. Conversely, regional atrophy measures did not show significant longitudinal changes between the two groups across six months. Our preliminary findings suggest that targeting DLPFC by rTMS application may lead to a significant long-term increase in FC in MCI patients in a RS network associated with executive functions, and this process might counteract the progressive cortical dysfunction affecting this domain.
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BACKGROUND AND PURPOSE: Although disabling fatigue is common in Parkinson disease (PD), available consensus-based diagnostic criteria have not yet been empirically validated. The aim of this study was to evaluate the clinimetric properties of the criteria. METHODS: A sample of outpatients with PD was evaluated for demographic, clinical, behavioral, and cognitive features. Fatigue was diagnosed according to the new diagnostic criteria and was rated by means of the Parkinson Fatigue Scale (PFS) and Fatigue Severity Scale (FSS). Acceptability, concurrent and discriminant validity, and interrater reliability were evaluated with binary logistic regression analyses and Cohen kappa (κ). RESULTS: Of 241 included patients, 17 (7.1%) met the diagnostic criteria for PD-related fatigue. Eight of nine symptoms described in Section A of the diagnostic criteria occurred in >50% of patients with fatigue. Acceptability (missing data = 0.8%) of the criteria was good, as was their concurrent validity with the PFS (odds ratio = 3.65) and FSS (odds ratio = 3.63). The discriminant validity of fatigue criteria with other PD-related behavioral and cognitive features was good (odds ratio < 1.68). The interrater reliability was excellent (κ = 0.92). CONCLUSIONS: This is the first study to test the clinimetric properties of case definition diagnostic criteria for PD-related fatigue. Our results suggest that current diagnostic criteria may be useful in both clinical practice and research. Future longitudinal studies should examine their long-term stability.
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Doença de Parkinson , Fadiga/diagnóstico , Fadiga/etiologia , Humanos , Doença de Parkinson/complicações , Doença de Parkinson/diagnóstico , Reprodutibilidade dos Testes , Índice de Gravidade de DoençaRESUMO
Caregivers of patients with early-onset Alzheimer's disease (EOAD) experience higher level of burden, stress, and depression, due to premature role changes and social isolation. Moreover, the SARS-CoV-2 pandemic compelled restrictions regarding social interactions and mobility in Italy from March 2020, prompting telemedicine approaches for supporting patients and their families confined at home. We reported our experience regarding the effects of psychological phone-intervention (phone-I) on EOAD caregivers during pandemic. Twenty caregivers of EOAD patients were randomly assigned to treatment (TG) or control (CG) group. TG weekly underwent a phone-I for one month. All participants were assessed for caregiver burden and needs, anxiety and depression levels, and subjective impact of traumatic events at baseline (T0), at the fifth week (T1) and after 6 months (T2) from phone-I. We observed higher vulnerability to post-traumatic stress in TG compared to CG in all timepoints (p ≤ 0.05). Decreased stress effects and caregiver burden were revealed in TG at T1 compared to T0 (p ≤ 0.05), although showing an increase of these measures at T2 in the treated caregivers. Our findings suggest that although TG showed a peculiar vulnerability to post-traumatic stress, they showed increased wellbeing immediately after phone-I. However, this benefit disappeared six months later, along with the second infection wave, probably due to "exhaustion stage" achievement in "General Adaptation Syndrome". This trend may suggest a beneficial but not solving role of a prompt phone-I on burden of caregivers of EOAD patients during the SARS-CoV-2 emergency.