- University of Brescia, Neurology, Faculty Memberadd
INTRODUCTION: Dementia with Lewy bodies (DLB) is typically characterized by parietal, temporal, and occipital atrophy, but less is known about the newly defined prodromal phases. The objective of this study was to evaluate structural... more
INTRODUCTION: Dementia with Lewy bodies (DLB) is typically characterized by parietal, temporal, and occipital atrophy, but less is known about the newly defined prodromal phases. The objective of this study was to evaluate structural brain alterations in prodromal DLB (p-DLB) as compared to healthy controls (HC) and full-blown dementia (DLB-DEM). METHODS: The study included 42 DLB patients (n = 20 p-DLB; n = 22 DLB-DEM) and 27 HC with a standardized neurological assessment and 3-tesla magnetic resonance imaging. Voxel-wise analyses on gray-matter and cortical thickness were implemented to evaluate differences between p-DLB, DLB-DEM, and HC. RESULTS: p-DLB and DLB-DEM exhibited reduced occipital and posterior parietotemporal volume and thickness, extending from prodromal to dementia stages.
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Recent studies suggest that COVID-19 survivors may experience long-term health consequences: in particular, neurological and mental health symptoms might be associated with long-term negative outcomes. This study is a secondary analysis... more
Recent studies suggest that COVID-19 survivors may experience long-term health consequences: in particular, neurological and mental health symptoms might be associated with long-term negative outcomes. This study is a secondary analysis of a larger cohort study and aims to determine the extent to which neurological and mental health sequelae are associated with survivors’ disability. Participants include COVID-19 survivors, with no pre-morbid brain conditions, who were discharged from the COVID-19 Unit of the ASST Spedali Civili Hospital between February and April 2020. At an average of 3.5 months after discharge, they were submitted to a neurological examination and completed the WHO Disability Assessment Schedule (WHODAS-12), the Hospital Anxiety and Depression Score, the Pittsburgh Sleep Quality Index and the Montreal Cognitive Assessment. Multivariable regression analysis was carried out to analyze variables that explain WHODAS-12 variation. In total, 83 patients (63 males, aver...
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The aim of this study is to assess changes in the body distribution and the semeiology of functional motor disorder (FMD) in patients who reported only one or more than one body site affected at FMD onset. Data were obtained from the... more
The aim of this study is to assess changes in the body distribution and the semeiology of functional motor disorder (FMD) in patients who reported only one or more than one body site affected at FMD onset. Data were obtained from the Italian Registry of Functional Motor Disorders, which included patients with a diagnosis of clinically definite FMDs. The relationship between FMD features and spread to other body sites was estimated by multivariate Cox regression analysis. We identified 201 (49%) patients who reported only one body site affected at FMD onset and 209 (51%) who reported multiple body sites affected at onset. FMD spread from the initial site to another site in 43/201 (21.4%) patients over 5.7 ± 7.1 years in those with only one site affected at FMD onset; FMD spread to an another body site in 29/209 (13.8%) over 5.5 ± 6.5 years. The spread of FMD was associated with non-motor functional symptoms and psychiatric comorbidities only in the patients with one body site affecte...
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Introduction The recently released classification has revised the nosology of tremor, defining essential tremor (ET) as a syndrome and fueling an enlightened debate about some newly conceptualized entities such as ET-plus. As a result,... more
Introduction The recently released classification has revised the nosology of tremor, defining essential tremor (ET) as a syndrome and fueling an enlightened debate about some newly conceptualized entities such as ET-plus. As a result, precise information of demographics, clinical features, and about the natural history of these conditions are lacking. Methods The ITAlian tremor Network (TITAN) is a multicenter data collection platform, the aim of which is to prospectively assess, according to a standardized protocol, the phenomenology and natural history of tremor syndromes. Results In the first year of activity, 679 patients have been recruited. The frequency of tremor syndromes varied from 32% of ET and 41% of ET-plus to less than 3% of rare forms, including focal tremors (2.30%), task-specific tremors (1.38%), isolated rest tremor (0.61%), and orthostatic tremor (0.61%). Patients with ET-plus were older and had a higher age at onset than ET, but a shorter disease duration, which...
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The selection of appropriate outcome measures is fundamental to the design of any successful clinical trial. Although dementia with Lewy bodies (DLB) is one of the most common neurodegenerative conditions, assessment of therapeutic... more
The selection of appropriate outcome measures is fundamental to the design of any successful clinical trial. Although dementia with Lewy bodies (DLB) is one of the most common neurodegenerative conditions, assessment of therapeutic benefit in clinical trials often relies on tools developed for other conditions, such as Alzheimer’s or Parkinson’s disease. These may not be sufficiently valid or sensitive to treatment changes in DLB, decreasing their utility. In this review, we discuss the limitations and strengths of selected available tools used to measure DLB-associated outcomes in clinical trials and highlight the potential roles for more specific objective measures. We emphasize that the existing outcome measures require validation in the DLB population and that DLB-specific outcomes need to be developed. Finally, we highlight how the selection of outcome measures may vary between symptomatic and disease-modifying therapy trials.
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ABSTRACTBackgroundFrailty is the most important short and long term predictor of disability in the elderly and thus might influence the clinical outcome of acute treatment of stroke.Objectiveto evaluate whether frailty predicts short- and... more
ABSTRACTBackgroundFrailty is the most important short and long term predictor of disability in the elderly and thus might influence the clinical outcome of acute treatment of stroke.Objectiveto evaluate whether frailty predicts short- and long term all-cause mortality and neurological recovery in elderly patients who underwent reperfusion acute treatment of stroke.Methodsthe study included consecutive patients older than 65 years who underwent reperfusion treatment in a single stroke Unit from 2015 to 2016. Predictors of stroke outcomes were assessed including demographics, baseline NIHSS, time to needle, treatment and medical complications. Premorbid Frailty was assessed with a comprehensive geriatric assessment (CGA) including functional, nutritional, cognitive, social and comorbidities status. At three and twelve months, all-cause death and clinical recovery (using modified Ranking scale, mRS) were evaluated.ResultsOne-hundred and two patients who underwent acute reperfusion trea...
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Objective To characterize patients with acute ischemic stroke related to SARS-CoV-2 infection and assess the classification performance of clinical and laboratory parameters in predicting in-hospital outcome of these patients. Methods In... more
Objective To characterize patients with acute ischemic stroke related to SARS-CoV-2 infection and assess the classification performance of clinical and laboratory parameters in predicting in-hospital outcome of these patients. Methods In the setting of the STROKOVID study including patients with acute ischemic stroke consecutively admitted to the ten hub hospitals in Lombardy, Italy, between March 8 and April 30, 2020, we compared clinical features of patients with confirmed infection and non-infected patients by logistic regression models and survival analysis. Then, we trained and tested a random forest (RF) binary classifier for the prediction of in-hospital death among patients with COVID-19. Results Among 1013 patients, 160 (15.8%) had SARS-CoV-2 infection. Male sex (OR 1.53; 95% CI 1.06–2.27) and atrial fibrillation (OR 1.60; 95% CI 1.05–2.43) were independently associated with COVID-19 status. Patients with COVID-19 had increased stroke severity at admission [median NIHSS sco...
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Background The COVID-19 pandemic leads to disruptions of health services worldwide. To evaluate the particular impact on neurological services a rapid review was conducted. Methods Studies reporting the provision of neurological services... more
Background The COVID-19 pandemic leads to disruptions of health services worldwide. To evaluate the particular impact on neurological services a rapid review was conducted. Methods Studies reporting the provision of neurological services during the pandemic and/or adopted mitigation strategies were included in this review. PubMed and World Health Organization’s (WHO) COVID-19 database were searched. Data extraction followed categories used by WHO COVID-19 pulse surveys and operational guidelines on maintaining essential health services during COVID-19. Findings The search yielded 1101 articles, of which 369 fulfilled eligibility criteria, describing data from 210,419 participants, being adults (81%), children (11.4%) or both (7.3%). Included articles reported data from 105 countries and territories covering all WHO regions and World Bank income levels (low income: 1.9%, lower middle: 24.7%, upper middle: 29.5% and high income; 44.8%). Cross-sectoral services for neurological disorde...
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Background Several preclinical and clinical investigations have argued for nervous system involvement in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Some sparse case reports have described various forms of... more
Background Several preclinical and clinical investigations have argued for nervous system involvement in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Some sparse case reports have described various forms of encephalitis in coronavirus disease 2019 (COVID-19) disease, but very few data have focused on clinical presentations, clinical course, response to treatment, and outcomes. Methods The SARS-CoV-2 related encephalopaties (ENCOVID) multicenter study included patients with encephalitis with full infectious screening, cerebrospinal fluid (CSF), electroencephalography (EEG), and magnetic resonance imaging (MRI) data and confirmed SARS-CoV-2 infection recruited from 13 centers in northern Italy. Clinical presentation and laboratory markers, severity of COVID-19 disease, response to treatment, and outcomes were recorded. Results Twenty-five cases of encephalitis positive for SARS-CoV-2 infection were included. CSF showed hyperproteinorrachia and/or pleocytosis...
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ABSTRACTImportanceSeveral preclinical and clinical investigations have argued for nervous system involvement in SARS-CoV-2 infection. Some sparse case reports have described various forms of encephalitis in COVID-19 disease, but very few... more
ABSTRACTImportanceSeveral preclinical and clinical investigations have argued for nervous system involvement in SARS-CoV-2 infection. Some sparse case reports have described various forms of encephalitis in COVID-19 disease, but very few data have focused on clinical presentations, clinical course, response to treatment and outcomes yet.Objectiveto describe the clinical phenotype, laboratory and neuroimaging findings of encephalitis associated with SARS-CoV-2 infection, their relationship with respiratory function and inflammatory parameters and their clinical course and response to treatment.DesignThe ENCOVID multicentre study was carried out in 13 centres in northern Italy between February 20th and May 31st, 2020. Only patients with altered mental status and at least two supportive criteria for encephalitis with full infectious screening, CSF, EEG, MRI data and a confirmed diagnosis of SARS-CoV-2 infection were included. Clinical presentation and laboratory markers, severity of CO...
Research Interests: Medicine and Encephalitis
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ABSTRACTBackgroundClinical investigations have argued for long-term neurological manifestations in both hospitalized and non-hospitalized COVID-19 patients. It is unclear whether long-term neurological symptoms and features depend on... more
ABSTRACTBackgroundClinical investigations have argued for long-term neurological manifestations in both hospitalized and non-hospitalized COVID-19 patients. It is unclear whether long-term neurological symptoms and features depend on COVID-19 severity.Methodsfrom a sample of 208 consecutive non-neurological patients hospitalized for COVID-19 disease, 165 survivors were re-assessed at 6 months according to a structured standardized clinical protocol. Prevalence and predictors of long-term neurological manifestations were evaluated using multivariate logistic regression analyses.ResultsAt 6-month follow-up after hospitalisation due to COVID-19 disease, patients displayed a wide array of symptoms; fatigue (34%), memory/attention (31%), and sleep disorders (30%) were the most frequent. At neurological examination, 40% of patients exhibited neurological abnormalities, such as hyposmia (18.0%), cognitive deficits (17.5%), postural tremor (13.8%) and subtle motor/sensory deficits (7.6%). O...
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Plasma neurofilament light chain (NfL) is a marker of neuronal damage in different neurological disorders and might predict disease progression in dementia with Lewy bodies (DLB). The study enrolled 45 controls and 44 DLB patients... more
Plasma neurofilament light chain (NfL) is a marker of neuronal damage in different neurological disorders and might predict disease progression in dementia with Lewy bodies (DLB). The study enrolled 45 controls and 44 DLB patients (including 17 prodromal cases) who underwent an extensive assessment at baseline and at 2 years follow-up. At baseline, plasma NfL levels were higher in both probable DLB and prodromal cases compared to controls. Plasma NfL emerged as the best predictor of cognitive decline compared to age, sex, and baseline severity variables. The study supports the role of plasma NfL as a useful prognostic biomarker from the early stages of DLB.
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Background Clinical investigations have argued for long-term neurological manifestations in both hospitalised and non-hospitalised COVID-19 patients. It is unclear whether long-term neurological symptoms and features depend on COVID-19... more
Background Clinical investigations have argued for long-term neurological manifestations in both hospitalised and non-hospitalised COVID-19 patients. It is unclear whether long-term neurological symptoms and features depend on COVID-19 severity. Methods From a sample of 208 consecutive non-neurological patients hospitalised for COVID-19 disease, 165 survivors were re-assessed at 6 months according to a structured standardised clinical protocol. Prevalence and predictors of long-term neurological manifestations were evaluated using multivariate logistic regression analyses. Results At 6-month follow-up after hospitalisation due to COVID-19 disease, patients displayed a wide array of symptoms; fatigue (34%), memory/attention (31%) and sleep disorders (30%) were the most frequent. At neurological examination, 40% of patients exhibited neurological abnormalities, such as hyposmia (18.0%), cognitive deficits (17.5%), postural tremor (13.8%) and subtle motor/sensory deficits (7.6%). Older...
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SUMMARYThere are no effective treatments for postural instability and falls in Progressive Supranuclear Palsy (PSP). Objective of the study was to test the efficacy of theta burst repetitive transcranial magnetic stimulation (rTMS) on... more
SUMMARYThere are no effective treatments for postural instability and falls in Progressive Supranuclear Palsy (PSP). Objective of the study was to test the efficacy of theta burst repetitive transcranial magnetic stimulation (rTMS) on postural instability in PSP. Twenty probable PSP patients underwent a session of sham or cerebellar rTMS in a cross-over design. Before and after stimulation, static balance was evaluated with instrumented (lower back accelerometer, Rehagait®, Hasomed, Germany) 30-seconds-trials in semitandem and tandem positions. In tandem and semitandem tasks, active stimulation was associated with longer time without support falls (both p=0.04). In the same tasks, device-extracted parameters revealed significant improvement in area (p=0.007), velocity (p=0.005) and acceleration and jerkiness of sway (p=0.008) in real versus sham stimulation. Cerebellar rTMS thus showed a significant effect on stability in PSP patients, when assessed with mobile digital technology, i...
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Falls are common among people with idiopathic Parkinson's disease (IPD) and are suggested to be associated with white matter hyperintensities (WMH) of the brain. To investigate the contribution of brain area-specific WMH to the risk... more
Falls are common among people with idiopathic Parkinson's disease (IPD) and are suggested to be associated with white matter hyperintensities (WMH) of the brain. To investigate the contribution of brain area-specific WMH to the risk of falls in IPD. In fifty participants with IPD, occurrence and severity of WMH in specific brain areas were determined using Scheltens (without lateralization) and Age-related white matter changes (ARWMC) (with lateralization) scores. Falls were evaluated with the fall item of the Unified PD Rating Scale (UPDRS). Correlations between area-specific WMH and falls were tested with stepwise backward regression and multivariate regression analyses. In this cohort of participants with IPD, left temporal WMH were associated with occurrence of falls. Frontal WMH of both hemispheres showed tendencies towards significance for the association with falls. According to our study, WMH in the left temporal area are significantly associated with falls in IPD. Poten...
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Alcohol, coffee, and tobacco consumption was assessed on 151 FTD outpatients and 151 matched controls in a multicenter retrospective case-control design. No association was found for smoking and coffee intake. The risk of FTD was... more
Alcohol, coffee, and tobacco consumption was assessed on 151 FTD outpatients and 151 matched controls in a multicenter retrospective case-control design. No association was found for smoking and coffee intake. The risk of FTD was decreased by alcohol consumption (adj. OR 0.30, 95% CI 0.14-0.63); risk reduction was significant in current alcohol consumers (adj. OR 0.22, 95% CI 0.10-0.51). The risk of FTD inversely correlated with the duration of exposure (adj. OR 0.88, 95% CI 0.81-0.95, for every 5 years of exposure increase). Retrospective information and the unknown amount of consumed alcohol are limits of the present work.
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Urinary dysfunction (UD) is a common non-motor feature of Parkinson's disease (PD), and might be secondary to neurodegeneration involving cortical and subcortical brain areas. The possible link between UD and cognitive deficits has... more
Urinary dysfunction (UD) is a common non-motor feature of Parkinson's disease (PD), and might be secondary to neurodegeneration involving cortical and subcortical brain areas. The possible link between UD and cognitive deficits has never been examined in frontal cortex impairment, and is still not completely understood in PD. In the present study, 94 PD patients underwent a comprehensive motor, cognitive and non-motor assessment. It was shown that 55.3% of patients reported UD, of which 17% needed specific urological treatment. Patients who reported UD performed worse on global cognition (PANDA, p = .05), visuo-constructive functions (CERAD/praxis, p = .03; and Figure Test, p = .03), and instrumental activities of daily living functions (IADL, p = .03), than patients without UD. The group with UD medication performed worse on global cognition (PANDA, p = .02) and visuo-constructive functions (CERAD/praxis, p = .05; CERAD/praxis recall, p = .05) than the UD group without medicati...
The research criteria for prodromal PD of the MDS propose a new approach for the assessment of the individual probability of prodromal PD. These criteria require a testing of their reliability in different prospective cohorts. The... more
The research criteria for prodromal PD of the MDS propose a new approach for the assessment of the individual probability of prodromal PD. These criteria require a testing of their reliability in different prospective cohorts. The objective was to evaluate the MDS prodromal PD criteria in 2 independent prospective studies. Prodromal PD probabilities of the Tübingen Evaluation of Risk Factors for Early Detection of Neurodegeneration cohort (TREND study, n = 650, recruited by the presence of probable rapid eye movement sleep behavior disorder, depression, and/or hyposmia or none of these at baseline and 2-, 4-, and 6-year follow-up) and the population-based Prospective Evaluation of Risk Factors for Idiopathic Parkinson's Syndrome cohort (PRIPS Tübingen subsample; n = 715, baseline and 3- and 5-year follow-up) were calculated. Baseline posttest probabilities, time to PD diagnosis, marker constellations, and longitudinal changes of prodromal PD probabilities were analyzed. Incident...
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Comprehensive geriatric assessment (CGA) is a multidisciplinary diagnostic and treatment process that identifies medical, psychosocial, and functional capabilities of older adults to develop a coordinated plan to maximize overall health... more
Comprehensive geriatric assessment (CGA) is a multidisciplinary diagnostic and treatment process that identifies medical, psychosocial, and functional capabilities of older adults to develop a coordinated plan to maximize overall health with aging. Specific criteria used by CGA programs to evaluate patients include age, medical comorbidities, psychosocial problems, previous or predicted high healthcare utilization, change in living situation, and specific geriatric conditions. However, no universal criteria have been agreed upon to readily identify patients who are likely to benefit from CGA. Evidence from randomized controlled trials and large systematic reviews and meta-analyses suggested that the healthcare setting may modify the effectiveness of CGA programs. Home CGA programs and CGA performed in the hospital were shown to be consistently beneficial for several health outcomes. In contrast, the data are conflicting for posthospital discharge CGA programs, outpatient CGA consultation, and CGA-based inpatient geriatric consultation services. The effectiveness of CGA programs may be modified also by particular settings or specific clinical conditions, with tailored CGA programs in older frail patients evaluated for preoperative assessment, admitted or discharged from emergency departments and orthogeriatric units or with cancer and cognitive impairment. CGA is capable of effectively exploring multiple domains in older age, being the multidimensional and multidisciplinary tool of choice to determine the clinical profile, the pathologic risk and the residual skills as well as the short- and long-term prognosis to facilitate the clinical decision making on the personalized care plan of older persons.
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Mild parkinsonian signs (MPS) are common in older people and are associated with an increased risk of different neurodegenerative diseases. This study prospectively evaluates the longitudinal course of cognitive performance in older... more
Mild parkinsonian signs (MPS) are common in older people and are associated with an increased risk of different neurodegenerative diseases. This study prospectively evaluates the longitudinal course of cognitive performance in older individuals with MPS. From the TREND study, 480 individuals neurologically healthy at baseline, aged between 50 and 80 years, with complete follow-up data for three assessments within a mean of 43.8 months, were included in this analysis. Participants underwent a detailed cognitive test battery, evaluation of prodromal markers for neurodegenerative diseases and history of vascular diseases at each study visit. In addition, plasma levels of amyloid-beta (Aβ)1-40 and Aβ1-42 were evaluated longitudinally. In 52 (11 %) of the 480 participants, MPS could be detected at baseline. These individuals had cognitive deficits significantly more often compared with controls at each time point and their cognitive performance showed a steeper decline during follow-up. ...
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To investigate the relationship between warfarin treatment and different strata of all-cause mortality risk assessed using the Multidimensional Prognostic Index (MPI) based on information collected using the Standardized Multidimensional... more
To investigate the relationship between warfarin treatment and different strata of all-cause mortality risk assessed using the Multidimensional Prognostic Index (MPI) based on information collected using the Standardized Multidimensional Assessment Schedule for Adults and Aged Persons (SVaMA) in community-dwelling older adults with atrial fibrillation (AF). Retrospective observational study. Older community-dwelling adults who underwent a SVaMA evaluation establishing accessibility to homecare services and nursing home admission from 2005 to 2013 in the Padova Health District, Italy. Community-dwelling individuals with AF aged 65 and older (N = 1,827). Participants were classified as being at mild (MPI-SVaMA-1), moderate (MPI-SVaMA-2), or severe (MPI-SVaMA-3) risk of mortality using the MPI-SVaMA, a validated prognostic tool based on age, sex, comorbidity, cognitive status, mobility and functional disability, pressure sore risk, and social support. The association between warfarin treatment and mortality was tested using multivariate- and propensity score-adjusted Cox regression models, controlling for age, sex, all SVaMA domains, concomitant diseases, and drug treatments. Higher MPI-SVaMA scores were associated with lower rates of warfarin treatment and higher 3-year mortality. After adjustment for propensity score quintiles, warfarin treatment was significantly associated with lower 2-year mortality in individuals with MPI-SVaMA-1 (hazard ratio (HR) = 0.64, 95% confidence interval (CI) = 0.50-0.82), MPI-SVaMA-2 (HR = 0.68, 95% CI = 0.55-0.85), and MPI-SVaMA-3 (HR = 0.55, 95% CI = 0.44-0.67). Heterogeneity analyses confirmed that the effect of warfarin treatment was not different between MPI-SVaMA groups (P for heterogeneity = .48). Community-dwelling older adults with AF benefitted from anticoagulation in terms of lower all-cause mortality over a mean follow-up of 2 years, regardless of poor health and functional condition. Although this benefit can be ascribed to the treatment, it may also reflect better overall care.
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Behavioral and cognitive impairment are common in amyotrophic lateral sclerosis (ALS) and represent a continuum with frontotemporal dementia (FTD). Olfactory dysfunction has been described in a subset of ALS patients and might be... more
Behavioral and cognitive impairment are common in amyotrophic lateral sclerosis (ALS) and represent a continuum with frontotemporal dementia (FTD). Olfactory dysfunction has been described in a subset of ALS patients and might be associated with frontotemporal and insular cortex dysfunction. To evaluate olfaction dysfunction in ALS patients and its relationship with either cognition or behavioral impairment. 28 consecutive ALS patients underwent an extensive cognitive and behavioral battery and were classified as patients with normal cognition (ALS-N, n = 11) or with part of the ALS-FTD spectrum (n = 17), including either cognitive or behavioral impairment or dementia. Odor verbal and visual identification and discrimination were investigated in patients and age-matched controls using a test adapted from the Sniffin' Sticks. Olfactory function was significantly different between ALS-FTD spectrum patients and controls (p < 0.001) and inversely correlated with behavioral and co...
Research Interests: Cognitive Science, Neurodegenerative Diseases, Amyotrophic Lateral Sclerosis, Humans, Female, and 14 moreSmell, Male, Clinical Sciences, Aged, Middle Aged, Frontotemporal Dementia, Olfactory perception, Cross Sectional Studies, Neurosciences, Cognition disorders, Neuropsychological Tests, Odorants, Neuro-Degenerative Diseases, and Olfaction disorders
Aim of this project was to evaluate autonomic dysfunction in subjects proposed to be at high risk to develop Parkinson's disease (PD) compared to control subjects and PD patients at different disease stages. Combinations of substantia... more
Aim of this project was to evaluate autonomic dysfunction in subjects proposed to be at high risk to develop Parkinson's disease (PD) compared to control subjects and PD patients at different disease stages. Combinations of substantia nigra hyperechogenicity (SN+) assessed by transcranial ultrasound (TCS), hyposmia, lifetime prevalence of depression and mild PD-specific motor signs were used to identify subjects at high risk for motor Parkinson's disease (HR-PD). Supine and standing blood pressure (BP), hearth rate (HR), orthostatic, urinary, sexual and bowel symptoms were evaluated in HR-PD, healthy control subjects and PD patients, divided into mild and advanced stages. The study group consisted of 113 PD patients (mild PD n = 71, advanced PD, n = 42), 40 HR-PD individuals and 50 controls. Compared to controls, HR-PD subjects complained more often about urinary (p = 0.002) and bowel dysfunction (p = 0.001) and had a higher diastolic BP drop after standing (p = 0.01). The c...
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A majority of current disease-modifying therapeutic approaches for age-related neurodegenerative diseases target their characteristic proteopathic lesions (α-synuclein, Tau, Aβ). To monitor such treatments, fluid biomarkers reflecting the... more
A majority of current disease-modifying therapeutic approaches for age-related neurodegenerative diseases target their characteristic proteopathic lesions (α-synuclein, Tau, Aβ). To monitor such treatments, fluid biomarkers reflecting the underlying disease process are crucial. We found robust increases of neurofilament light chain (NfL) in CSF and blood in murine models of α-synucleinopathies, tauopathy, and β-amyloidosis. Blood and CSF NfL levels were strongly correlated, and NfL increases coincided with the onset and progression of the corresponding proteopathic lesions in brain. Experimental induction of α-synuclein lesions increased CSF and blood NfL levels, while blocking Aβ lesions attenuated the NfL increase. Consistently, we also found NfL increases in CSF and blood of human α-synucleinopathies, tauopathies, and Alzheimer's disease. Our results suggest that CSF and particularly blood NfL can serve as a reliable and easily accessible biomarker to monitor disease progress...
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Vascular risk factors have been associated with cognitive deficits and incident dementia in the general population, but their role on cognitive dysfunction in Parkinson's disease (PD) is still unclear. The present study addresses the... more
Vascular risk factors have been associated with cognitive deficits and incident dementia in the general population, but their role on cognitive dysfunction in Parkinson's disease (PD) is still unclear. The present study addresses the single and cumulative effect of vascular risk factors on cognition in PD patients, taking clinical confounders into account. Standardized neuropsychological assessment was performed in 238 consecutive PD patients. We evaluated the association of single and cumulative vascular risk factors (smoking, diabetes, hypercholesterolemia, hypertension, and heart disease), with the diagnosis of PD normal cognition (PDNC, n = 94), mild cognitive impairment (PD-MCI, n = 111), and dementia (PDD, n = 33). The association between single neuropsychological tests and vascular risk factors was evaluated with covariance analyses adjusted for age at onset, educational levels, gender, disease duration, and motor performance. Age, educational levels, disease duration, an...
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The early stages of behavioral variant frontotemporal dementia (bvFTD) are still not completely characterized. In a consecutive series of patients with probable bvFTD diagnosis confirmed by follow-up, we retrospectively evaluated the... more
The early stages of behavioral variant frontotemporal dementia (bvFTD) are still not completely characterized. In a consecutive series of patients with probable bvFTD diagnosis confirmed by follow-up, we retrospectively evaluated the features at onset. Patients were reclassified according to presenting features and current diagnostic criteria into probable and possible bvFTD. The term &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;pre-bvFTD&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; was adopted for patients with cognitive and/or behavioral impairment not fulfilling bvFTD criteria and no deficits in activities of daily living. One hundred ninety-four subjects were included; at first visit, 70% (n = 136) patients were already classified as probable bvFTD. Of the remaining 30% (n = 58), 60% fulfilled criteria for possible bvFTD, while 40% did not, and were classified as pre-FTD. The neuropsychological pattern in possible bvFTD and pre-bvFTD was similar, although possible bvFTD showed more behavioral abnormalities. Pre-bvFTD subjects had frontotemporal gray matter atrophy, although less extensive than possible bvFTD. Conclusively, most bvFTD patients fulfill current diagnostic criteria at first admission, whereas a relatively small group is characterized by mild behavioral and/or cognitive abnormalities in spite of frontotemporal gray matter atrophy. Our preliminary findings will require a validation in prospective studies involving larger samples of patients.