Publications by authors named "Andrea Pilotto"

105 Publications

Plasma NfL, clinical subtypes and motor progression in Parkinson's disease.

Parkinsonism Relat Disord 2021 Apr 27;87:41-47. Epub 2021 Apr 27.

Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.

Introduction: neurofilament light chain (NfL) levels have been proposed as reliable biomarkers of neurodegeneration in Parkinson's disease (PD) but the relationship between plasma NfL, clinical subtypes of PD and motor progression is still debated.

Methods: plasma NfL concentration was measured in 45 healthy controls and consecutive 92 PD patients who underwent an extensive motor and non-motor assessment at baseline and after 2 years of follow-up. PD malignant phenotype was defined as the combination of at least two out of cognitive impairment, orthostatic hypotension and REM sleep behavior disorder. PD patients were divided according to the age-adjusted cut-offs of plasma NfL levels into high and normal NfL (H-NfL and N-NfL, respectively). A multivariable linear regression model was used to assess the value of plasma NfL as predictor of 2-years progression in PD.

Results: NfL was higher in PD patients than in controls (p = 0.037). H-NfL (n = 16) group exhibited more severe motor and non-motor symptoms, higher prevalence of malignant phenotype and worse motor progression (MDS-UPDRS-III 11.3 vs 0.7 points, p = 0.003) compared to N-NfL group (n = 76). In linear regression analyses plasma NfL emerged as the best predictor of 2-year motor progression compared to age, sex, disease duration, baseline motor/non-motor variables.

Conclusion: increased plasma NfL concentration is associated with malignant PD phenotype and faster motor progression. These findings support the role of NfL assessment as a useful measure for stratifying patients with different baseline slopes of decline in future clinical trials of putative disease-modifying treatments.
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http://dx.doi.org/10.1016/j.parkreldis.2021.04.016DOI Listing
April 2021

Functional motor phenotypes: to lump or to split?

J Neurol 2021 May 7. Epub 2021 May 7.

IRCCS Mondino Foundation, Pavia, Italy.

Introduction: Functional motor disorders (FMDs) are usually categorized according to the predominant phenomenology; however, it is unclear whether this phenotypic classification mirrors the underlying pathophysiologic mechanisms.

Objective: To compare the characteristics of patients with different FMDs phenotypes and without co-morbid neurological disorders, aiming to answer the question of whether they represent different expressions of the same disorder or reflect distinct entities.

Methods: Consecutive outpatients with a clinically definite diagnosis of FMDs were included in the Italian registry of functional motor disorders (IRFMD), a multicenter data collection platform gathering several clinical and demographic variables. To the aim of the current work, data of patients with isolated FMDs were extracted.

Results: A total of 176 patients were included: 58 with weakness, 40 with tremor, 38 with dystonia, 23 with jerks/facial FMDs, and 17 with gait disorders. Patients with tremor and gait disorders were older than the others. Patients with functional weakness had more commonly an acute onset (87.9%) than patients with tremor and gait disorders, a shorter time lag from symptoms onset and FMDs diagnosis (2.9 ± 3.5 years) than patients with dystonia, and had more frequently associated functional sensory symptoms (51.7%) than patients with tremor, dystonia and gait disorders. Patients with dystonia complained more often of associated pain (47.4%) than patients with tremor. No other differences were noted between groups in terms of other variables including associated functional neurological symptoms, psychiatric comorbidities, and predisposing or precipitating factors.

Conclusions: Our data support the evidence of a large overlap between FMD phenotypes.
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http://dx.doi.org/10.1007/s00415-021-10583-wDOI Listing
May 2021

Agitation and Dementia: Prevention and Treatment Strategies in Acute and Chronic Conditions.

Front Neurol 2021 16;12:644317. Epub 2021 Apr 16.

Department of Neuroscience, Imaging and Clinical Sciences, University G. d'Annunzio of Chieti-Pescara, Chieti, Italy.

Agitation is a behavioral syndrome characterized by increased, often undirected, motor activity, restlessness, aggressiveness, and emotional distress. According to several observations, agitation prevalence ranges from 30 to 50% in Alzheimer's disease, 30% in dementia with Lewy bodies, 40% in frontotemporal dementia, and 40% in vascular dementia (VaD). With an overall prevalence of about 30%, agitation is the third most common neuropsychiatric symptoms (NPS) in dementia, after apathy and depression, and it is even more frequent (80%) in residents of nursing homes. The pathophysiological mechanism underlying agitation is represented by a frontal lobe dysfunction, mostly involving the anterior cingulate cortex (ACC) and the orbitofrontal cortex (OFC), respectively, meaningful in selecting the salient stimuli and subsequent decision-making and behavioral reactions. Furthermore, increased sensitivity to noradrenergic signaling has been observed, possibly due to a frontal lobe up-regulation of adrenergic receptors, as a reaction to the depletion of noradrenergic neurons within the locus coeruleus (LC). Indeed, LC neurons mainly project toward the OFC and ACC. These observations may explain the abnormal reactivity to weak stimuli and the global arousal found in many patients who have dementia. Furthermore, agitation can be precipitated by several factors, e.g., the sunset or low lighted environments as in the sundown syndrome, hospitalization, the admission to nursing residencies, or changes in pharmacological regimens. In recent days, the global pandemic has increased agitation incidence among dementia patients and generated higher distress levels in patients and caregivers. Hence, given the increasing presence of this condition and its related burden on society and the health system, the present point of view aims at providing an extensive guide to facilitate the identification, prevention, and management of acute and chronic agitation in dementia patients.
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http://dx.doi.org/10.3389/fneur.2021.644317DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085397PMC
April 2021

The multidimensional prognostic index (MPI) for the prognostic stratification of older inpatients with COVID-19: A multicenter prospective observational cohort study.

Arch Gerontol Geriatr 2021 Apr 5;95:104415. Epub 2021 Apr 5.

Department of Primary Care, District 3, ULSS 3, Venice, Italy,; Department of Internal Medicine and Geriatrics, University of Palermo, Italy. Electronic address:

Background: The topic of prognosis in COVID-19 research may be important in adopting appropriate clinical decisions. Multidimensional prognostic index (MPI) is a frailty assessment tool widely used for stratifying prognosis in older people, but data regarding inpatients, affected by COVID-19, are not available.

Objectives: To evaluate whether MPI can predict in-hospital mortality and the admission to intensive care unit (ICU) in older inpatients hospitalized for COVID-19 infection.

Methods: In this longitudinal, Italian, multi-center study, older patients with COVID-19 were included. MPI was calculated using eight different domains typical of comprehensive geriatric assessment and categorized in three groups (MPI 1 ≤ 0.33, MPI 2 0.34-0.66, MPI 3 > 0.66). A multivariable Cox's regression analysis was used reporting the results as hazard ratios (HRs) with 95% confidence intervals (CIs).

Results: 227 older patients hospitalized for SARS-CoV-2 infection were enrolled (mean age: 80.5 years, 59% females). Inpatients in the MPI 3 were subjected less frequently than those in the MPI 1 to non-invasive ventilation (NIV). In the multivariable analysis, people in MPI 3 experienced a higher risk of in hospital mortality (HR = 6.30, 95%CI: 1.44-27.61), compared to MPI 1. The accuracy of MPI in predicting in hospital mortality was good (Area Under the Curve (AUC) = 0.76, 95%CI: 0.68-0.83). People in MPI 3 experienced a significant longer length of stay (LOS) in hospital compared to other participants. No association between MPI and ICU admission was found.

Conclusions: Frailty- as assessed by high MPI score - was associated with a significant higher risk of in-hospital mortality, longer LOS, and lower use NIV, whilst the association with ICU admission was not significant. These findings suggest that prognostic stratification by using the MPI could be useful in clinical decision making in older inpatients affected by COVID-19.
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http://dx.doi.org/10.1016/j.archger.2021.104415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020604PMC
April 2021

Alterations of frontal-temporal gray matter volume associate with clinical measures of older adults with COVID-19.

Neurobiol Stress 2021 May 13;14:100326. Epub 2021 Apr 13.

Department of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta, USA.

COVID-19, the infectious disease caused by the most recently discovered severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has become a global pandemic. It dramatically affects people's health and daily life. Neurological complications are increasingly documented for patients with COVID-19. However, the effect of COVID-19 on the brain is less studied, and existing quantitative neuroimaging analyses of COVID-19 were mainly based on the univariate voxel-based morphometry analysis (VBM) that requires corrections for a large number of tests for statistical significance, multivariate approaches that can reduce the number of tests to be corrected have not been applied to study COVID-19 effect on the brain yet. In this study, we leveraged source-based morphometry (SBM) analysis, a multivariate extension of VBM, to identify changes derived from computed tomography scans in covarying gray matter volume patterns underlying COVID-19 in 120 neurological patients (including 58 cases with COVID-19 and 62 patients without COVID-19 matched for age, gender and diseases). SBM identified that lower gray matter volume (GMV) in superior/medial/middle frontal gyri was significantly associated with a higher level of disability (modified Rankin Scale) at both discharge and six months follow-up phases even when controlling for cerebrovascular diseases. GMV in superior/medial/middle frontal gyri was also significantly reduced in patients receiving oxygen therapy compared to patients not receiving oxygen therapy. Patients with fever presented significant GMV reduction in inferior/middle temporal gyri and fusiform gyrus compared to patients without fever. Patients with agitation showed GMV reduction in superior/medial/middle frontal gyri compared to patients without agitation. Patients with COVID-19 showed no significant GMV differences from patients without COVID-19 in any brain region. Results suggest that COVID-19 may affect the frontal-temporal network in a secondary manner through fever or lack of oxygen.
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http://dx.doi.org/10.1016/j.ynstr.2021.100326DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041745PMC
May 2021

Validation of α-Synuclein in L1CAM-Immunocaptured Exosomes as a Biomarker for the Stratification of Parkinsonian Syndromes.

Mov Disord 2021 Apr 7. Epub 2021 Apr 7.

Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford, UK.

Background: Parkinson's disease is characterized by intraneuronal α-synuclein aggregation. Currently there is no α-synuclein-based blood test in clinical practice.

Objectives: Our aim was to assess by means of further testing and analysis whether α-synuclein measurements in serum L1CAM-immunocaptured exosomes can differentiate Parkinson's disease from related movement disorders.

Methods: We used poly(carboxybetaine-methacrylate)-coated magnetic beads to isolate L1CAM-positive exosomes and triplexed electrochemiluminescence to measure exosomal α-synuclein, clusterin, and syntenin-1 from 267 serum samples. Combined analysis of our current and previously published data from the Oxford, Kiel, Brescia, and PROSPECT cohorts consisting of individuals (total n = 735) with Parkinson's disease (n = 290), multiple system atrophy (MSA, n = 50), progressive supranuclear palsy (n = 116), corticobasal syndrome (n = 88), and healthy controls (n = 191) was done using 2-stage (training vs validation) receiver operating characteristic analysis.

Results: We established that α-synuclein level in L1CAM-immunocaptured exosomes above 14 pg/mL is a robust biomarker across cohorts that distinguishes Parkinson's disease from MSA (AUC, 0.90 vs 0.98) or 4-repeat tauopathies (AUC, 0.93 vs 0.94). We confirmed that exosomal clusterin is elevated in subjects with 4-repeat tauopathy, and when combined with α-synuclein, it improved the performance of the assay in differentiating Parkinson's disease from 4-repeat tauopathies to AUC, 0.98 versus 0.99. Correction for the generic exosomal protein syntenin-1 did not consistently improve the performance of the assay.

Conclusions: α-Synuclein and clusterin in L1CAM-immunocaptured serum exosomes is a validated blood test for the molecular stratification of neuronal α-synucleinopathy (ie, Lewy body pathology) versus phenotypically related neurodegenerative movement disorders. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.28591DOI Listing
April 2021

Impact of SARS-CoV-2 on reperfusion therapies for acute ischemic stroke in Lombardy, Italy: the STROKOVID network.

J Neurol 2021 Mar 8. Epub 2021 Mar 8.

Department of Neurology and Stroke Unit, Carlo Poma Hospital, ASST Mantova, Mantua, Italy.

Whether and how SARS-CoV-2 outbreak affected in-hospital acute stroke care system is still matter of debate. In the setting of the STROKOVID network, a collaborative project between the ten centers designed as hubs for the treatment of acute stroke during SARS-CoV-2 outbreak in Lombardy, Italy, we retrospectively compared clinical features and process measures of patients with confirmed infection (COVID-19) and non-infected patients (non-COVID-19) who underwent reperfusion therapies for acute ischemic stroke. Between March 8 and April 30, 2020, 296 consecutive patients [median age, 74 years (interquartile range (IQR), 62-80.75); males, 154 (52.0%); 34 (11.5%) COVID-19] qualified for the analysis. Time from symptoms onset to treatment was longer in the COVID-19 group [230 (IQR 200.5-270) minutes vs. 190 (IQR 150-245) minutes; p = 0.007], especially in the first half of the study period. Patients with COVID-19 who underwent endovascular thrombectomy had more frequently absent collaterals or collaterals filling ≤ 50% of the occluded territory (50.0% vs. 16.6%; OR 5.05; 95% CI 1.82-13.80) and a lower rate of good/complete recanalization of the primary arterial occlusive lesion (55.6% vs. 81.0%; OR 0.29; 95% CI 0.10-0.80). Post-procedural intracranial hemorrhages were more frequent (35.3% vs. 19.5%; OR 2.24; 95% CI 1.04-4.83) and outcome was worse among COVID-19 patients (in-hospital death, 38.2% vs. 8.8%; OR 6.43; 95% CI 2.85-14.50). Our findings showed longer delays in the intra-hospital management of acute ischemic stroke in COVID-19 patients, especially in the early phase of the outbreak, that likely impacted patients outcome and should be the target of future interventions.
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http://dx.doi.org/10.1007/s00415-021-10497-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937781PMC
March 2021

Cerebellar rTMS in PSP: a Double-Blind Sham-Controlled Study Using Mobile Health Technology.

Cerebellum 2021 Feb 5. Epub 2021 Feb 5.

Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, P.zale Spedali Civili, 1, 25123, Brescia, Italy.

There are no effective treatments in progressive supranuclear palsy (PSP). The aim of this study was to test the efficacy of theta burst repetitive transcranial magnetic stimulation (rTMS) on postural instability in PSP. Twenty PSP patients underwent a session of sham or real cerebellar rTMS in a crossover design. Before and after stimulation, static balance was evaluated with instrumented (lower back accelerometer, Rehagait®, Hasomed, Germany) 30-s trials in semitandem and tandem positions. In tandem and semitandem tasks, active stimulation was associated with increase in time without falls (both p=0.04). In the same tasks, device-extracted parameters revealed significant improvement in area (p=0.007), velocity (p=0.005), acceleration and jerkiness of sway (p=0.008) in real versus sham stimulation. Cerebellar rTMS showed a significant effect on stability in PSP patients, when assessed with mobile digital technology, in a double-blind design. These results should motivate larger and longer trials using non-invasive brain stimulation for PSP patients.
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http://dx.doi.org/10.1007/s12311-021-01239-6DOI Listing
February 2021

Associations among education, age, and the dementia with Lewy bodies (DLB) metabolic pattern: A European-DLB consortium project.

Alzheimers Dement 2021 Feb 2. Epub 2021 Feb 2.

Nuclear Medicine Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.

Introduction: We assessed the influence of education as a proxy of cognitive reserve and age on the dementia with Lewy bodies (DLB) metabolic pattern.

Methods: Brain 18F-fluorodeoxyglucose positron emission tomography and clinical/demographic information were available in 169 probable DLB patients included in the European DLB-consortium database. Principal component analysis identified brain regions relevant to local data variance. A linear regression model was applied to generate age- and education-sensitive maps corrected for Mini-Mental State Examination score, sex (and either education or age).

Results: Age negatively covaried with metabolism in bilateral middle and superior frontal cortex, anterior and posterior cingulate, reducing the expression of the DLB-typical cingulate island sign (CIS). Education negatively covaried with metabolism in the left inferior parietal cortex and precuneus (making the CIS more prominent).

Discussion: These findings point out the importance of tailoring interpretation of DLB biomarkers considering the concomitant effect of individual, non-disease-related variables such as age and cognitive reserve.
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http://dx.doi.org/10.1002/alz.12294DOI Listing
February 2021

MicroRNA‑34a‑5p expression in the plasma and in its extracellular vesicle fractions in subjects with Parkinson's disease: An exploratory study.

Int J Mol Med 2021 Feb 2;47(2):533-546. Epub 2020 Dec 2.

Department of Molecular and Translational Medicine, University of Brescia, I‑25123 Brescia, Italy.

Parkinson's disease (PD) is an important disabling age‑related disorder and is the second most common neurodegenerative disease. Currently, no established molecular biomarkers exist for the early diagnosis of PD. Circulating microRNAs (miRNAs), either vesicle‑free or encapsulated in extracellular vesicles (EVs), have emerged as potential blood‑based biomarkers also for neurodegenerative diseases. In this exploratory study, we focused on miR‑34a‑5p because of its well‑documented involvement in neurobiology. To explore a differential profile of circulating miR‑34a‑5p in PD, PD patients and age‑matched control subjects were enrolled. Serial ultracentrifugation steps and density gradient were used to separate EV subpopulations from plasma according to their different sedimentation properties (Large, Medium, Small EVs). Characterization of EV types was performed using western blotting and atomic force microscopy (AFM); purity from protein contaminants was checked with the colorimetric nanoplasmonic assay. Circulating miR‑34a‑5p levels were evaluated using qPCR in plasma and in each EV type. miR‑34a‑5p was significantly up‑regulated in small EVs devoid of exogenous protein contaminants (pure SEVs) from PD patients and ROC analysis indicated a good diagnostic performance in discriminating patients from controls (AUC=0.74, P<0.05). Moreover, miR‑34a‑5p levels in pure SEVs were associated with disease duration, Hoehn and Yahr and Beck Depression Inventory scores. These results underline the necessity to examine the miRNA content of each EV subpopulation to identify miRNA candidates with potential diagnostic value and lay the basis for future studies to validate the overexpression of circulating miR‑34a‑5p in PD via the use of pure SEVs.
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http://dx.doi.org/10.3892/ijmm.2020.4806DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797475PMC
February 2021

Reply to Abboud.

J Infect Dis 2021 Apr;223(7):1304-1305

Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.

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http://dx.doi.org/10.1093/infdis/jiab007DOI Listing
April 2021

SARS-CoV-2 encephalitis is a cytokine release syndrome: evidences from cerebrospinal fluid analyses.

Clin Infect Dis 2021 Jan 4. Epub 2021 Jan 4.

Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Italy.

Background: Recent findings indicated that SARS-CoV-2 related neurological manifestations involve cytokine release syndrome along with endothelial activation, blood brain barrier dysfunction, and immune-mediated mechanisms. Very few studies have fully investigated the CSF correlates of SARS-CoV-2 encephalitis.

Methods: Patients with PCR-confirmed SARS-CoV-2 infection and encephalitis (COV-Enc), encephalitis without SARS-CoV-2 infection (ENC) and healthy controls (HC) underwent an extended panel of CSF neuronal (NfL, T-tau), glial (GFAP, TREM2, YKL-40) and inflammatory biomarkers (IL-1β, IL-6, Il-8, TNF- α, CXCL-13 and β2-microglobulin).

Results: Thirteen COV-Enc, 21 ENC and 18 HC entered the study. In COV-Enc cases, CSF was negative for SARS-CoV-2 real-time PCR but exhibited increased IL-8 levels independently from presence of pleocytosis/hyperproteinorracchia. COV-Enc patients showed increased IL-6, TNF- α, and β2-microglobulin and glial markers (GFAP, sTREM-2, YKL-40) levels similar to ENC but normal CXCL13 levels. Neuronal markers NfL and T-Tau were abnormal only in severe cases.

Conclusions: SARS-CoV-2-related encephalitis were associated with prominent glial activation and neuroinflammatory markers, whereas neuronal markers were increased in severe cases only. The pattern of CSF alterations suggested a cytokine-release syndrome as the main inflammatory mechanism of SARS-CoV-2 related encephalitis.
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http://dx.doi.org/10.1093/cid/ciaa1933DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7799260PMC
January 2021

Metal Exposure and SNCA rs356219 Polymorphism Associated With Parkinson Disease and Parkinsonism.

Front Neurol 2020 9;11:556337. Epub 2020 Dec 9.

Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.

In the province of Brescia, Italy, historical neurotoxic metal exposure has occurred for several decades. This study aimed to explore the role of metal exposure and genetics on Parkinson's Disease (PD) and Parkinsonism. Cases were enrolled from four local clinics for movement disorders. Randomly selected controls non-affected by neurological or psychiatric conditions were enrolled from the same health centers keeping a similar gender ratio and age distribution as for cases. Data on sociodemographic variables, clinical onset and life habits were collected besides accurate occupational and residential history. Blood samples were collected from all participants for genotyping of target polymorphisms in genes linked to PD and/or metal transport. A total number of 432 cases and 444 controls were enrolled in the study, with average age of 71 years (72.2 for cases and 70 for controls). The average age at diagnosis was 65.9 years (SD 9.9). Among the potential risk factors, family history of PD or Parkinsonism showed the strongest association with the diseases (OR = 4.2, 95% CI 2.3, 7.6 on PD; OR = 4.3, 95% CI 1.9, 9.5 for Parkinsonism), followed by polymorphism rs356219 in the alpha-synuclein () gene (OR = 2.03, 95% CI 1.3, 3.3 for CC vs. TT on PD; OR = 2.5, 95% CI 1.1, 5.3 for CC vs. TT on Parkinsonism), exposure to metals (OR = 2.4;, 95% CI 1.3, 4.2 on PD), being born in a farm (OR = 1.8; 95% CI 1.1, 2.8 on PD; OR = 2.6; 95% CI 1.4, 4.9 on Parkinsonism) and being born in the province of Brescia (OR = 1.7; 95% CI 1.0, 2.9 on PD). Conditional OR of having PD depending by polymorphism and metal exposure highlights higher risk of PD among CC carriers and being exposed to metals. However, the interaction term was not statistically significant. Lifetime exposure to metals and genetic variation in gene are relevant determinants of PD and Parkinsonism in the highly industrialized area of Brescia, Italy. The lack of evidence of statistical interaction between environmental and genetic factors may be due to the low frequencies of subjects representing the exposure categories and the polymorphism variants and does not rule out the biological interaction.
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http://dx.doi.org/10.3389/fneur.2020.556337DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7755861PMC
December 2020

Functional motor disorders associated with other neurological diseases: Beyond the boundaries of "organic" neurology.

Eur J Neurol 2021 May 2;28(5):1752-1758. Epub 2021 Jan 2.

Movement Disorder Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

Background And Purpose: The aims of this study were to describe the clinical manifestations of functional motor disorders (FMDs) coexisting with other neurological diseases ("comorbid FMDs"), and to compare comorbid FMDs with FMDs not overlapping with other neurological diseases ("pure FMDs").

Methods: For this multicenter observational study, we enrolled outpatients with a definite FMD diagnosis attending 25 tertiary movement disorder centers in Italy. Each patient with FMDs underwent a detailed clinical assessment including screening for other associated neurological conditions. Group comparisons (comorbid FMDs vs. pure FMDs) were performed in order to compare demographic and clinical variables. Logistic regression models were created to estimate the adjusted odds ratios (95% confidence intervals) of comorbid FMDs (dependent variable) in relation to sociodemographic and clinical characteristics (independent variables).

Results: Out of 410 FMDs, 21.7% of patients (n = 89) had comorbid FMDs. The most frequent coexisting neurological diseases were migraine, cerebrovascular disease and parkinsonism. In the majority of cases (86.5%), FMDs appeared after the diagnosis of a neurological disease. Patients with comorbid FMDs were older, and more frequently had tremor, non-neurological comorbidities, paroxysmal non-epileptic seizures, major depressive disorders, and benzodiazepine intake. Multivariate regression analysis showed that diagnosis of comorbid FMDs was more likely associated with longer time lag until the final diagnosis of FMD, presence of tremor and non-neurological comorbidities.

Conclusions: Our findings highlight the need for prompt diagnosis of FMDs, given the relatively high frequency of associated neurological and non-neurological diseases.
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http://dx.doi.org/10.1111/ene.14674DOI Listing
May 2021

Association of Hippocampal Subfields, CSF Biomarkers, and Cognition in Patients With Parkinson Disease Without Dementia.

Neurology 2021 02 20;96(6):e904-e915. Epub 2020 Nov 20.

From the Department of Neurodegenerative Diseases (S.B., B.R., I.L.-S.), Hertie Institute for Clinical Brain Research; German Center for Neurodegenerative Diseases (S.B., B.R., I.L.-S.), Tübingen; Department of Neurology (O.G., W.M., D.B.), Christian-Albrechts-University, Kiel, Germany; Janssen Research and Development, a Division of Janssen Pharmaceutica N.V. (M.T., L.V.N., J.S.), Beerse; Reference Center for Biological Markers of Dementia (M.T.), Institute Born-Bunge, University of Antwerp, Belgium; Department of Clinical and Experimental Sciences (A.P.), University of Brescia; Parkinson's Disease Rehabilitation Centre (A.P.), FERB ONLUS Sant'Isidoro Hospital, Trescore Balneario, Italy; Janssen Research and Development LLC (G.S., W.R.G.), Titusville, NJ; Translational Medicine Neuroscience (J.S.), UCB Biopharma SPRK, Braine-l'Alleud, Belgium; Magnetic Resonance Center (K.S.), Max Planck Institute for Biological Cybernetics; and Department of Biomedical Magnetic Resonance (K.S.), University Hospital Tübingen, Germany.

Objective: To examine whether hippocampal volume loss is primarily associated with cognitive status or pathologic β-amyloid 1-42 (Aβ42) levels, this study compared hippocampal subfield volumes between patients with Parkinson disease (PD) with mild cognitive impairment (PD-MCI) and without cognitive impairment (PD-CN) and between patients with low and high Aβ42 levels, in addition exploring the relationship among hippocampal subfield volumes, CSF biomarkers (Aβ42, phosphorylated and total tau), neuropsychological tests, and activities of daily living.

Methods: Forty-five patients with PD without dementia underwent CSF analyses and MRI as well as comprehensive motor and neuropsychological examinations. Hippocampal segmentation was conducted using FreeSurfer image analysis suite 6.0. Regression models were used to compare hippocampal subfield volumes between groups, and partial correlations defined the association between variables while controlling for intracranial volume (ICV).

Results: Linear regressions revealed cognitive group as a statistically significant predictor of both the hippocampal-amygdaloid transition area (HATA; β = -0.23, 95% CI -0.44 to -0.02) and the cornu ammonis 1 region (CA1; β = -0.28, 95% confidence interval [CI] -0.56 to -0.02), independent of disease duration and ICV, with patients with PD-MCI showing significantly smaller volumes than PD-CN. In contrast, no subfields were predicted by Aβ42 levels. Smaller hippocampal volumes were associated with worse performance on memory, language, spatial working memory, and executive functioning tests. The subiculum was negatively correlated with total tau levels ( = -0.37, 95% CI -0.60 to -0.09).

Conclusion: Cognitive status, but not CSF Aβ42, predicted hippocampal volumes, specifically the CA1 and HATA. Hippocampal subfields were associated with various cognitive domains, as well as with tau pathology.
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http://dx.doi.org/10.1212/WNL.0000000000011224DOI Listing
February 2021

Gender-Related Vulnerability of Dopaminergic Neural Networks in Parkinson's Disease.

Brain Connect 2021 Feb 23;11(1):3-11. Epub 2020 Dec 23.

Vita-Salute San Raffaele University, Milan, Italy.

In Parkinson's disease (PD), neurodegeneration of dopaminergic systems leads to motor and non-motor abnormalities. Sex might influence the clinical PD phenotypes and progression. Previous molecular imaging data focused only on the nigro-striato-cortical dopamine system that appeared more preserved in women. There is still a lack of evidence on gender/sex differences in the mesolimbic dopaminergic system. We aimed at assessing PD gender differences in both the dopaminergic pathways, by using a brain metabolic connectivity approach. This is based on the evidence of a significant coupling between the neurotransmission and metabolic impairments. We included 34 idiopathic PD patients (Female/Male: 16/18) and 34 healthy controls for comparison. The molecular architecture of both the dopaminergic networks was estimated throughout partial correlation analyses using brain metabolism data obtained by fluorine-18-fluorodeoxyglucose positron emission tomography (threshold set at  < 0.01, corrected for Bonferroni multiple comparisons). Male patients were characterized by a widespread altered connectivity in the nigro-striato-cortical network and a sparing of the mesolimbic pathway. On the contrary, PD females showed a severe altered connectivity in the mesolimbic network and only a partial reconfiguration of the nigro-striato-cortical network. Our findings add remarkable knowledge on the neurobiology of gender differences in PD, with the identification of specific neural vulnerabilities. The gender differences here revealed might be due to the combination of both biological and sociodemographic life factors. Gender differences in PD should be considered also for treatments and the targeting of modifiable risk factors.
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http://dx.doi.org/10.1089/brain.2020.0781DOI Listing
February 2021

Clinical Correlates of Functional Motor Disorders: An Italian Multicenter Study.

Mov Disord Clin Pract 2020 Nov 22;7(8):920-929. Epub 2020 Sep 22.

Department of Systems Medicine University of Rome Tor Vergata Rome Italy.

Background: Functional motor disorders (FMDs) are abnormal movements that are significantly altered by distractive maneuvers and are incongruent with movement disorders seen in typical neurological diseases.

Objective: The objectives of this article are to (1) describe the clinical manifestations of FMDs, including nonmotor symptoms and occurrence of other functional neurological disorders (FND); and (2) to report the frequency of isolated and combined FMDs and their relationship with demographic and clinical variables.

Methods: For this multicenter, observational study, we enrolled consecutive outpatients with a definite diagnosis of FMDs attending 25 tertiary movement disorders centers in Italy. Each patient underwent a detailed clinical evaluation with a definition of the phenotype and number of FMDs (isolated, combined) and an assessment of associated neurological and psychiatric symptoms.

Results: Of 410 FMDs (71% females; mean age, 47 ± 16.1 years) the most common phenotypes were weakness and tremor. People with FMDs had higher educational levels than the general population and frequent nonmotor symptoms, especially anxiety, fatigue, and pain. Almost half of the patients with FMDs had other FNDs, such as sensory symptoms, nonepileptic seizures, and visual symptoms. Patients with combined FMDs showed a higher burden of nonmotor symptoms and more frequent FNDs. Multivariate regression analysis showed that a diagnosis of combined FMDs was more likely to be delivered by a movement disorders neurologist. Also, FMD duration, pain, insomnia, diagnosis of somatoform disease, and treatment with antipsychotics were all significantly associated with combined FMDs.

Conclusions: Our findings highlight the need for multidimensional assessments in patients with FMDs given the high frequency of nonmotor symptoms and other FNDs, especially in patients with combined FMDs.
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http://dx.doi.org/10.1002/mdc3.13077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7604660PMC
November 2020

Impaired metabolic brain networks associated with neurotransmission systems in the α-synuclein spectrum.

Parkinsonism Relat Disord 2020 12 21;81:113-122. Epub 2020 Oct 21.

School of Psychology, Vita-Salute San Raffaele University, Milan, Italy; In Vivo Human Molecular and Structural Neuroimaging Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; Nuclear Medicine Unit, San Raffaele Hospital, Milan, Italy. Electronic address:

Introduction: While the involvement of multiple neurotransmitter systems in α-synucleinopathies is reported, a comprehensive study on their metabolic connectivity reconfiguration in the preclinical and clinical disease-spectrum is lacking. We aimed to investigate shared and disease-specific neural vulnerabilities of the nigro-striato-cortical dopaminergic, noradrenergic and cholinergic networks within the α-synuclein-spectrum, by means of metabolic connectivity approach.

Methods: We collected 34 polysomnography-confirmed isolated REM sleep behaviour disorder (iRBD) subjects, 29 idiopathic Parkinson's disease (PD) patients without dementia, 30 patients with probable dementia with Lewy bodies (DLB), and 50 healthy controls for comparisons. Neurotransmission networks' analyses were performed through multivariate partial correlations based on FDG-PET brain metabolic data.

Results: We found: a) the nigro-striato-cortical dopaminergic network with a limited reconfiguration in individuals with iRBD, but moderate-to-severe alterations in patients with DLB and PD; b) an extended connectivity alteration of the noradrenergic network in all groups; c) changes within the cholinergic networks connectivity in the whole disease-spectrum, with some differences: PD with only moderate connectivity reconfiguration and DLB with the most severe alterations, some of these shared with iRBD.

Conclusions: Synucleinopathies can be considered multisystem disorders, with common and disease-specific neurotransmission networks reconfigurations. The present findings indicate dopaminergic connectivity alterations only when associated with parkinsonism, a very early involvement of noradrenergic networks, occurring in both the iRBD and in symptomatic PD/DLB patients and cholinergic alterations with disease-specific vulnerabilities shared by iRBD and DLB. The latter finding may represent an early biomarker of disease progression to dementia.
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http://dx.doi.org/10.1016/j.parkreldis.2020.10.036DOI Listing
December 2020

Phenylalanine Effects on Brain Function in Adult Phenylketonuria.

Neurology 2021 01 22;96(3):e399-e411. Epub 2020 Oct 22.

From the Neurology Unit (A. Pilotto, A. Padovani), Department of Clinical and Experimental Sciences, University of Brescia, Italy; Department of Neurodegeneration (A. Pilotto, I.L.-S., K.B., W.M., C.S., C.D., A.K.H., D.B.), Hertie Institute of Clinical Brain Research (A. Pilotto, C.M.Z., I.L.-S., K.B., W.M., C.S., C.D., A.K.H., D.B.), Department of Neurology and Stroke (C.M.Z.), Department of Biomedical Magnetic Resonance (E.L., K.S.), and German Center for Neurodegenerative Diseases (I.L.-S., K.B., C.S., C.D., A.K.H., K.S.), University of Tübingen, Germany; Parkinson's Disease Rehabilitation Centre (A. Pilotto), FERB ONLUS, S. Isidoro Hospital, Trescore Balneario, Italy; Department of Pediatrics (D.H., G.G., G.F.H., F.T.), Division for Neuropediatrics and Metabolic Medicine, University of Heidelberg; Department of Pediatrics (P.F., F.T.), Reutlingen Hospital; Department of Neurology (E.S., W.M., D.B.), University-Hospital-Schleswig-Holstein, Campus Kiel, Christian-Albrechts-University Kiel; and Division of Metabolic Diseases (F.J.v.S.), Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, the Netherlands.

Objective: To evaluate the relationship between circulating phenylalanine and brain function as well as neuropsychiatric symptoms in adults with phenylketonuria.

Methods: In this prospective cross-sectional study, early-treated patients with phenylketonuria older than 30 years and age- and sex-matched controls were included. Extensive neurologic evaluation, neuropsychological and behavioral testing, sensory and motor evoked potentials, and MRI were performed. CSF concentrations of neurodegenerative markers were evaluated in addition in a subset of 10 patients.

Results: Nineteen patients with phenylketonuria (median age 41 years) with different phenylalanine levels (median 873 μmol/L) entered the study. They showed higher prevalence of neurologic symptoms, cognitive and behavioral abnormalities, autonomic dysfunction, alterations in neurophysiologic measures, and atrophy in putamen and right thalamus compared to controls. In CSF, patients with phenylketonuria exhibited higher β-amyloid 1-42 ( = 0.003), total tau ( < 0.001), and phosphorylated tau ( = 0.032) levels compared to controls. Plasma phenylalanine levels highly correlated with the number of failed neuropsychological tests ( = 0.64, = 0.003), neuropsychiatric symptoms ( = 0.73, < 001), motor evoked potential latency ( = 0.48, = 0.030), and parietal lobe atrophy.

Conclusions: Our study provides strong evidence for a correlation between phenylalanine levels and clinical, neuropsychological, neurophysiologic, biochemical, and imaging alterations in adult patients with phenylketonuria.
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http://dx.doi.org/10.1212/WNL.0000000000011088DOI Listing
January 2021

Rivastigmine in Parkinson's Disease Dementia with Orthostatic Hypotension.

Ann Neurol 2021 01 20;89(1):91-98. Epub 2020 Oct 20.

Neuroscience Translational Medicine, Novartis Institutes for Biomedical Research, Neurology, and Neurosurgery, McGill University, Montreal, Quebec, Canada.

Objective: The purpose of this study was to evaluate if the cognitive benefit of rivastigmine is affected by the presence of orthostatic hypotension (OH) in patients with Parkinson's disease dementia (PDD).

Methods: We conducted a post hoc analysis on 1,047 patients with PDD from 2 randomized controlled trials comparing rivastigmine versus placebo at week 24 (n = 501) and rivastigmine patch versus capsule at week 76 (n = 546). A drop ≥ 20 mm Hg in systolic blood pressure (SBP) or ≥ 10 in diastolic blood pressure (DBP) upon standing classified subjects as OH positive (OH+); otherwise, OH negative (OH-). The primary end point was the Alzheimer's Disease Assessment Scale - Cognitive subscale (ADAS-Cog) at week 24 and the Mattis Dementia Rating Scale (MDRS) at week 76, using intention-to-treat with retrieved dropout at week 24 and observed cases at week 76, consistent with the original analyses.

Results: Overall safety was comparable between OH+ (n = 288, 27.5%) and OH- (n = 730, 69.7%), except for higher frequency of syncope (9.2%) in the OH+ placebo arm. The placebo-adjusted effect of rivastigmine on ADAS-Cog at week 24 was 5.6 ± 1.2 for OH+ and 1.9 ± 0.9 in OH- (p = 0.0165). Among subjects with OH, the MDRS change from baseline at week 76 was higher for rivastigmine capsules versus patch (10.6 ± 2.9 vs -1.5 ± 3.0, p = 0.031). The overall prevalence of OH was lower for rivastigmine than placebo at week 24 (28.3% vs 44.6%, p = 0.0476).

Interpretation: The cognitive benefit from rivastigmine is larger in patients with PDD with OH, possibly mediated by a direct antihypotensive effect. ANN NEUROL 2021;89:91-98.
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http://dx.doi.org/10.1002/ana.25923DOI Listing
January 2021

Looking at the burden of neurological disorders in Europe.

Lancet Public Health 2020 10;5(10):e523

Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia 25123, Italy; Parkinson's Disease Rehabilitation Centre, FERB ONLUS, S Isidoro Hospital, Trescore Balneario, Bergamo, Italy.

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http://dx.doi.org/10.1016/S2468-2667(20)30205-XDOI Listing
October 2020

Clinical Presentation and Outcomes of Severe Acute Respiratory Syndrome Coronavirus 2-Related Encephalitis: The ENCOVID Multicenter Study.

J Infect Dis 2021 01;223(1):28-37

Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.

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 in 68% of cases whereas SARS-CoV-2 RNA by reverse-transcription polymerase chain reaction resulted negative. Based on MRI, cases were classified as acute demyelinating encephalomyelitis (ADEM; n = 3), limbic encephalitis (LE; n = 2), encephalitis with normal imaging (n = 13), and encephalitis with MRI alterations (n = 7). ADEM and LE cases showed a delayed onset compared to the other encephalitis cases (P = .001) and were associated with previous, more severe COVID-19 respiratory involvement. Patients with MRI alterations exhibited worse response to treatment and final outcomes compared to those with other encephalitis.

Conclusions: SARS-CoV-2 infection is associated with a wide spectrum of encephalitis characterized by different clinical presentation, response to treatment, and outcomes.
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http://dx.doi.org/10.1093/infdis/jiaa609DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7543535PMC
January 2021

Reply to the Letter "COVID-19-Associated Encephalopathy and Cytokine-Mediated Neuroinflammation".

Ann Neurol 2020 10 14;88(4):861-862. Epub 2020 Aug 14.

Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.

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http://dx.doi.org/10.1002/ana.25856DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7436670PMC
October 2020

Implementation of Mobile Health Technologies in Clinical Trials of Movement Disorders: Underutilized Potential.

Neurotherapeutics 2020 10;17(4):1736-1746

Gardner Family Center for Parkinson's disease and Movement Disorders, Department of Neurology, University of Cincinnati Academic Health Center, 260 Stetson St., Suite 2300, Cincinnati, OH, 45267-0525, USA.

Mobile health technologies (mHealth) are patient-worn or portable devices aimed at increasing the granularity and relevance of clinical measurements. The implementation of mHealth has the potential to decrease sample size, duration, and cost of clinical trials. We performed a review of the ClinicalTrials.gov database using a standardized approach to identify adoption in and usefulness of mHealth in movement disorders interventional clinical trials. Trial phase, geographical area, availability of data captured, constructs of interest, and outcome priority were collected. Eligible trials underwent quality appraisal using an ad hoc 5-point checklist to assess mHealth feasibility, acceptability, correlation with patient-centered outcome measures, and clinical meaningfulness. A total of 29% (n = 54/184) registered trials were using mHealth, mainly in Parkinson's disease and essential tremor (59.3% and 27.8%). In most cases, mHealth were used in phase 2 trials (83.3%) as secondary outcome measures (59.3%). Only five phase 3 trials, representing 9.3% of the total, used mHealth (1 as primary outcome measure, 3 as secondary, and 1 as tertiary). Only 3.7% (n = 2/54) of all trials used mHealth for measuring both motor and non-motor symptoms, and 23.1% (n = 12/52) used mHealth for unsupervised, ecologic outcomes. Our findings suggest that mHealth remain underutilized and largely relegated to phase 2 trials for secondary or tertiary outcome measures. Efforts toward greater alignment of mHealth with patient-centered outcomes and development of a universal, common-language platform to synchronize data from one or more devices will assist future efforts toward the integration of mHealth into clinical trials.
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http://dx.doi.org/10.1007/s13311-020-00901-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851293PMC
October 2020

The combined effect of amyloid-β and tau biomarkers on brain atrophy in dementia with Lewy bodies.

Neuroimage Clin 2020 2;27:102333. Epub 2020 Jul 2.

Centre for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway; Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.

Background: Alzheimer's disease (AD)-related pathology is frequently found in patients with dementia with Lewy bodies (DLB). However, it is unknown how amyloid-β and tau-related pathologies influence neurodegeneration in DLB. Understanding the mechanisms underlying brain atrophy in DLB can improve our knowledge about disease progression, differential diagnosis, drug development and testing of anti-amyloid and anti-tau therapies in DLB.

Objectives: We aimed at investigating the combined effect of CSF amyloid-β42, phosphorylated tau and total tau on regional brain atrophy in DLB in the European DLB (E-DLB) cohort.

Methods: 86 probable DLB patients from the E-DLB cohort with CSF and MRI data were included. Random forest was used to analyze the association of CSF biomarkers (predictors) with visual rating scales for medial temporal lobe atrophy (MTA), posterior atrophy (PA) and global cortical atrophy scale-frontal subscale (GCA-F) (outcomes), including age, sex, education and disease duration as extra predictors.

Results: DLB patients with abnormal MTA scores had abnormal CSF Aβ42, shorter disease duration and older age. DLB patients with abnormal PA scores had abnormal levels of CSF Aβ42 and p-tau, older age, lower education and shorter disease duration. Abnormal GCA-F scores were associated with lower education, male sex, and older age, but not with any AD-related CSF biomarker.

Conclusions: This study shows preliminary data on the potential combined effect of amyloid-β and tau-related pathologies on the integrity of posterior brain cortices in DLB patients, whereas only amyloid-β seems to be related to MTA. Future availability of α-synuclein biomarkers will help us to understand the effect of α-synuclein and AD-related pathologies on brain integrity in DLB.
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http://dx.doi.org/10.1016/j.nicl.2020.102333DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7363702PMC
July 2020

The effect of age and gender on anti-saccade performance: Results from a large cohort of healthy aging individuals.

Eur J Neurosci 2020 11 5;52(9):4165-4184. Epub 2020 Jul 5.

Department of Cognitive Neurology, Hertie Institute for Clinical Brain Research (HIH), University of Tübingen, Tübingen, Germany.

By 2050, the global population of people aged 65 years or older will triple. While this is accompanied with an increasing burden of age-associated diseases, it also emphasizes the need to understand the effects of healthy aging on cognitive processes. One such effect is a general slowing of processing speed, which is well documented in many domains. The execution of anti-saccades depends on a well-established brain-wide network ranging from various cortical areas and basal ganglia through the superior colliculus down to the brainstem saccade generators. To clarify the consequences of healthy aging as well as gender on the execution of reflexive and voluntary saccades, we measured a large sample of healthy, non-demented individuals (n = 731, aged 51-84 years) in the anti-saccade task. Age affected various aspects of saccade performance: The number of valid trials decreased with age. Error rate, saccadic reaction times (SRTs), and variability in saccade accuracy increased with age, whereas anti-saccade costs, accuracy, and peak velocity of anti-saccades and direction errors were not affected by age. Gender affected SRTs independent of age and saccade type with male participants having overall shorter SRTs. Our rigid and solid statistical testing using linear mixed-effect models provide evidence for a uniform slowing of processing speed independent of the actually performed eye movement. Our data do not support the assumption of a specific deterioration of frontal lobe functions with aging.
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http://dx.doi.org/10.1111/ejn.14878DOI Listing
November 2020

Benign versus malignant Parkinson disease: the unexpected silver lining of motor complications.

J Neurol 2020 Oct 2;267(10):2949-2960. Epub 2020 Jun 2.

Department of Neurology, Gardner Family Center for Parkinson's Disease and Movement Disorders, University of Cincinnati, Cincinnati, OH, USA.

Objective: We sought to evaluate demographic, clinical, and habits/occupational variables between phenotypic extremes in Parkinson's disease (PD).

Methods: Databases from nine movement disorders centers across seven countries were retrospectively searched for subjects meeting criteria for very slowly progressive, benign, PD (bPD) and rapidly progressive, malignant, PD (mPD). bPD was defined as Hoehn and Yahr (H&Y) stage ≤ 3, normal cognitive function, and Schwab and England (S&E) score ≥ 70 after ≥ 20 years of PD (≥ 10 years if older than 60 at PD onset); mPD as H&Y > 3, S&E score < 70, and cognitive impairment within 10 years from PD onset. We performed between-group analysis of demographic, habits/occupational, and clinical features at baseline and follow-up and unsupervised data-driven analysis of the clinical homogeneity of bPD and mPD.

Results: At onset, bPD subjects (n = 210) were younger, had a single limb affected, lower severity and greater asymmetry of symptoms, and lower prevalence of depression than mPD (n = 155). bPD was associated with active smoking and physical activity, mPD with agricultural occupation. At follow-up, mPD showed higher prevalence of depression, hallucinations, dysautonomia, and REM behaviour disorder. Interestingly, the odds of mPD were significantly reduced by the presence of dyskinesia and wearing-off. Data-driven analysis confirmed the independent clustering of bPD and mPD, with age at onset emerging as a critical discriminant between the two groups (< 46-year-old vs. > 68-year-old).

Conclusions: Phenotypic PD extremes showed distinct demographic, clinical, and habits/occupational factors. Motor complications may be conceived as markers of therapeutic success given their attenuating effects on the odds of mPD.
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http://dx.doi.org/10.1007/s00415-020-09954-6DOI Listing
October 2020

Anterior EEG slowing in dementia with Lewy bodies: a multicenter European cohort study.

Neurobiol Aging 2020 09 29;93:55-60. Epub 2020 Apr 29.

Department of Neuroscience, Imaging and Clinical Science, and Aging Research Centre, G. d'Annunzio University of Chieti-Pescara, Chieti, Italy. Electronic address:

Electroencephalography (EEG) slowing with prealpha dominant frequency (DF) in posterior derivations is a biomarker for dementia with Lewy bodies (DLB) diagnosis, in contrast with Alzheimer's disease (AD). However, an intrasubject re-evaluation of the original data, which contributed to the identification of EEG DLB biomarker, showed that DF was slower in anterior than posterior derivations. We suppose this anterior-posterior gradient of DF slowing could arise in DLB from a thalamocortical dysrhythmia, differently involving the anterior and posterior cortical areas, and correlating with cognitive impairment (Mini-Mental State Examination). EEG was recorded in 144 DLB, 116 AD, and 65 controls from 7 Centers of the European DLB Consortium. Spectra were divided into delta, theta, prealpha, alpha frequency bands. In DLB, mean DF was prealpha both anteriorly and posteriorly, but lower anteriorly (p < 0.001). In 14% of DLB, DF was prealpha anteriorly, whereas alpha posteriorly. In AD and controls, DF was constantly alpha. EEG slowing in DLB correlated with cognitive impairment. Thalamocortical dysrhythmia gives rise to prealpha rhythm with an anterior-posterior gradient and correlates with impaired cognition.
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http://dx.doi.org/10.1016/j.neurobiolaging.2020.04.023DOI Listing
September 2020