Publications by authors named "Elisabetta Cottini"

11 Publications

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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

Clinical characteristics and outcomes of inpatients with neurologic disease and COVID-19 in Brescia, Lombardy, Italy.

Neurology 2020 08 22;95(7):e910-e920. Epub 2020 May 22.

From the Neurology Unit (A.B., A. Pilotto, I.L., M.G., E.B., S.B., M.C., S.C.P., V.C., A.I., M. Locatelli, S.M., B.R., L.R., A.S., F.S.d.C., N.Z., B.B., A. Pezzini, A. Padovani), Department of Clinical and Experimental Sciences, University of Brescia; Neurology Unit (A.B., A. Pilotto, C.A., A.A., S.C., E.C., M.F., S. Gipponi, P.L., L.P., R.R., L.R., I.V., B.B., A. Pezzini, A. Padovani), Vascular Neurology Unit (E.P., A.C., I.D., M.G., N.G., R.S., V.V., M.M.), and Neurophysiology Unit (S. Gazzina, U.L.), Department of Neurological and Vision Sciences, ASST Spedali Civili, Brescia; Neurology Unit (M.B.), University of Bologna; Department of Neuroimmunology and Neuromuscular Diseases (L.B.) and Neurology (M. Leonardi), Public Health and Disability Unit, Foundation IRCCS Neurological Institute Carlo Besta, Milan; and Neurology Unit (P.I.), Fondazione Poliambulanza Hospital, Brescia, Italy.

Objective: To report clinical and laboratory characteristics, treatment, and clinical outcomes of patients admitted for neurologic diseases with and without coronavirus disease 2019 (COVID-19).

Methods: In this retrospective, single-center cohort study, we included all adult inpatients with confirmed COVID-19 admitted to a neuro-COVID unit beginning February 21, 2020, who had been discharged or died by April 5, 2020. Demographic, clinical, treatment, and laboratory data were extracted from medical records and compared (false discovery rate corrected) to those of neurologic patients without COVID-19 admitted in the same period.

Results: One hundred seventy-three patients were included in this study, of whom 56 were positive and 117 were negative for COVID-19. Patients with COVID-19 were older (77.0 years, interquartile range [IQR] 67.0-83.8 years vs 70.1 years, IQR 52.9-78.6 years, = 0.006), had a different distribution regarding admission diagnoses, including cerebrovascular disorders (n = 43, 76.8% vs n = 68, 58.1%), and had a higher quick Sequential Organ Failure Assessment (qSOFA) score on admission (0.9, IQR 0.7-1.1 vs 0.5, IQR 0.4-0.6, = 0.006). In-hospital mortality rates (n = 21, 37.5% vs n = 5, 4.3%, < 0.001) and incident delirium (n = 15, 26.8% vs n = 9, 7.7%, = 0.003) were significantly higher in the COVID-19 group. Patients with COVID-19 and without COVID with stroke had similar baseline characteristics, but patients with COVID-19 had higher modified Rankin Scale scores at discharge (5.0, IQR 2.0-6.0 vs 2.0, IQR 1.0-3.0, < 0.001), with a significantly lower number of patients with a good outcome (n = 11, 25.6% vs n = 48, 70.6%, < 0.001). In patients with COVID-19, multivariable regressions showed increasing odds of in-hospital death associated with higher qSOFA scores (odds ratio [OR] 4.47, 95% confidence interval [CI] 1.21-16.5, = 0.025), lower platelet count (OR 0.98, 95% CI 0.97-0.99, = 0.005), and higher lactate dehydrogenase (OR 1.01, 95% CI 1.00-1.03, = 0.009) on admission.

Conclusions: Patients with COVID-19 admitted with neurologic disease, including stroke, have a significantly higher in-hospital mortality and incident delirium and higher disability than patients without COVID-19.
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http://dx.doi.org/10.1212/WNL.0000000000009848DOI Listing
August 2020

Extrastriatal dopaminergic and serotonergic pathways in Parkinson's disease and in dementia with Lewy bodies: a I-FP-CIT SPECT study.

Eur J Nucl Med Mol Imaging 2019 Jul 16;46(8):1642-1651. Epub 2019 May 16.

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

Purpose: The aim of the study was to evaluate extrastriatal dopaminergic and serotonergic pathways in patients with Parkinson's disease (PD) and dementia with Lewy bodies (DLB) using I-FP-CIT SPECT imaging.

Methods: The study groups comprised 56 PD patients without dementia, 41 DLB patients and 54 controls. Each patient underwent a standardized neurological examination and I-FP-CIT SPECT. Binding in nigrostriatal and extrastriatal regions of interest was calculated in each patient from spatially normalized images. The occipital-adjusted specific to nondisplaceable binding ratio (SBR) in the different regions was compared among the PD patients, DLB patients and controls adjusting for the effects of age, sex, disease duration and serotonergic/dopaminergic treatment. Covariance analysis was used to determine the correlates of local and long-distance regions with extrastriatal I-FP-CIT deficits.

Results: Both PD and DLB patients showed lower I-FP-CIT SPECT SBR in several regions beyond the nigrostriatal system, especially the insula, cingulate and thalamus. DLB patients showed significantly lower I-FP-CIT SBR in the thalamus than controls and PD patients. Thalamic and cingulate I-FP-CIT SBR deficits were correlated, respectively, with limbic serotonergic and widespread cortical monoaminergic projections only in DLB patients but exhibited only local correlations in PD patients and controls.

Conclusion: PD and DLB patients both showed insular dopamine deficits, whereas impairment of thalamic serotonergic pathways was specifically associated with DLB. Longitudinal studies are necessary to determine the clinical value of the assessment of extrastriatal I-FP-CIT SPECT.
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http://dx.doi.org/10.1007/s00259-019-04324-5DOI Listing
July 2019

Vascular Risk Factors and Cognition in Parkinson's Disease.

J Alzheimers Dis 2016 ;51(2):563-70

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

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, and motor function were significantly different between PDNC, PD-MCI, and PDD. Heart disease was the only vascular factor significantly more prevalent in PDD compared with PDNC in adjusted analyses. Performance of tests assessing executive and attention functions were significantly worse in patients with hypertension, heart disease, and/or diabetes (p <  0.05). Heart disease is associated with dementia in PD, suggesting a potential window of intervention. Vascular risk factors act especially on attention and executive functions in PD. Vascular risk stratification may be useful in order to identify PD patients with a greater risk of developing dementia. These findings need to be verified in longitudinal studies.
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http://dx.doi.org/10.3233/JAD-150610DOI Listing
December 2016

Structural and functional imaging study in dementia with Lewy bodies and Parkinson's disease dementia.

Parkinsonism Relat Disord 2015 Sep 16;21(9):1049-55. Epub 2015 Jun 16.

Centre for Ageing Brain and Neurodegenerative Disorders, Neurology Unit, University of Brescia, Italy.

Introduction: Dementia with Lewy Bodies (DLB) and Parkinson's disease with Dementia (PDD) are neurodegenerative disorders with complex clinical picture (parkinsonism, cognitive decline and neuropsychiatric disturbances). The conundrum of whether DLB and PDD represent the same or different entities is still under debate. Advanced neuroimaging techniques may represent a point of view to assess brain correlates in DLB and PDD. The study aimed at evaluating whether DLB and PDD may be labelled under the same disease entity or be considered distinctive pathologies. We compared DLB and PDD patients by assessing structural and functional brain imaging and including PD patients.

Methods: Patients with diagnosis of PD, PDD, DLB and a group of healthy controls for neuroimaging comparisons were recruited and changes in structural and resting-state functional MR (Regional Homogeneity, ReHo) were studied.

Results: No significant atrophy in VBM analysis was evident in PD. Conversely, PDD showed a significant bilateral frontal atrophy, whereas DLB was characterized by a predominant parietal, occipital atrophy; a similar involvement of subcortical regions in PDD and DLB was observed. ReHo demonstrated reduced local coherence of frontal regions in PD and in PDD, whereas DLB patients presented a reduced local connectivity in posterior regions.

Conclusion: Different brain areas are specifically involved in PDD and DLB. In the former group, greater atrophy of frontal regions with concomitant functional connectivity impairment was evident; conversely, structural and functional damage in the posterior regions characterized DLB. Despite an overlapping clinical spectrum, DLB and PDD have different networks involved and different underlying pathogenic pathways.
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http://dx.doi.org/10.1016/j.parkreldis.2015.06.013DOI Listing
September 2015

Structural and functional imaging study in dementia with Lewy bodies and Parkinson's disease dementia.

Parkinsonism Relat Disord 2015 Sep 16;21(9):1049-55. Epub 2015 Jun 16.

Centre for Ageing Brain and Neurodegenerative Disorders, Neurology Unit, University of Brescia, Italy.

Introduction: Dementia with Lewy Bodies (DLB) and Parkinson's disease with Dementia (PDD) are neurodegenerative disorders with complex clinical picture (parkinsonism, cognitive decline and neuropsychiatric disturbances). The conundrum of whether DLB and PDD represent the same or different entities is still under debate. Advanced neuroimaging techniques may represent a point of view to assess brain correlates in DLB and PDD. The study aimed at evaluating whether DLB and PDD may be labelled under the same disease entity or be considered distinctive pathologies. We compared DLB and PDD patients by assessing structural and functional brain imaging and including PD patients.

Methods: Patients with diagnosis of PD, PDD, DLB and a group of healthy controls for neuroimaging comparisons were recruited and changes in structural and resting-state functional MR (Regional Homogeneity, ReHo) were studied.

Results: No significant atrophy in VBM analysis was evident in PD. Conversely, PDD showed a significant bilateral frontal atrophy, whereas DLB was characterized by a predominant parietal, occipital atrophy; a similar involvement of subcortical regions in PDD and DLB was observed. ReHo demonstrated reduced local coherence of frontal regions in PD and in PDD, whereas DLB patients presented a reduced local connectivity in posterior regions.

Conclusion: Different brain areas are specifically involved in PDD and DLB. In the former group, greater atrophy of frontal regions with concomitant functional connectivity impairment was evident; conversely, structural and functional damage in the posterior regions characterized DLB. Despite an overlapping clinical spectrum, DLB and PDD have different networks involved and different underlying pathogenic pathways.
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http://dx.doi.org/10.1016/j.parkreldis.2015.06.013DOI Listing
September 2015

Headache: Prevalence and relationship with office or ambulatory blood pressure in a general population sample (the Vobarno Study).

Blood Press 2006 ;15(1):14-9

Internal Medicine, Department of Medical and Surgical Sciences, University of Brescia, Brescia, Italy.

Unlabelled: The association of headache and arterial hypertension is still controversial, although headache is usually considered a symptom of hypertension. The aim of this study is to evaluate the prevalence of headache in a general population sample and the relationship with arterial hypertension, as diagnosed by office measurements and ambulatory monitoring of blood pressure (BP).

Patients And Methods: In the randomized sample of the Vobarno population, 301 subjects (126 males, 175 females, age range 35-50 years) underwent a structured standardized headache questionnaire, office and 24-h ambulatory BP monitoring.

Results: Prevalence of lifetime headache and of migraine was greater in females than in males. Office and 24-h BP values did not differ between subjects without headache and subjects with headache. No differences in headache prevalence (58% vs 55%), migraine prevalence (32% vs 28%) and use of analgesic drugs in the presence of headache (82% vs 78%) were observed between hypertensive patients (93.5% newly diagnosed, 6.5% treated) and normotensive subjects.

Conclusions: In a general population sample, hypertension (diagnosed by office and/or 24-h BP) is not associated with headache.
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http://dx.doi.org/10.1080/08037050500436089DOI Listing
June 2006

Is transient global amnesia a risk factor for amnestic mild cognitive impairment?

J Neurol 2004 Sep;251(9):1125-7

Dipto. Scienze Mediche e Chirurgiche, Clinica Neurologica-Università degli Studi di Brescia, Piazza Spedali Civili 1, 25100, Brescia, Italy.

Transient Global Amnesia (TGA) is a common condition of unknown aetiology characterised by the abrupt onset of severe anterograde amnesia, which lasts less than 24 hours. Some authors have suggested that subclinical impairment of memory functions may persist for much longer, but neuropsychological assessment lasting years after TGA attack has not been performed so far. The aim of this study was to evaluate longterm cognitive functions in patients with a previous TGA episode. Fifty-five patients underwent a standardised neuropsychological assessment after at least one-year from the TGA attack, and were compared with 80 age-matched controls. TGA patients showed worse performances on tests evaluating verbal and nonverbal long-term memory and attention, with comparable global cognitive functions. By applying current criteria for amnestic Mild Cognitive Impairment (MCI-a) on TGA subjects, a group consisting of 18/55 (32.7%) MCI-a subjects was identified. There was no association between the presence of MCI-a and demographic variables, vascular risk factors, years since the TGA episode, or ApoE genotype. This study demonstrates that TGA appears to be a relatively benign syndrome although objective memory deficits fulfilling MCI-a criteria persist over time, as detected by multidimensional neuropsychological tasks performed at long-term follow-up.
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http://dx.doi.org/10.1007/s00415-004-0497-xDOI Listing
September 2004

Is mild vascular cognitive impairment reversible? Evidence from a study on the effect of carotid endarterectomy.

Neurol Res 2004 Jul;26(5):594-7

Department of Medical Sciences, Neurological Clinic, University of Brescia, Italy.

Mild vascular cognitive impairment (mVCI) is a broader term that is intended to detect cognitive loss before the development of dementia. The identification of preventable risk factors as well as therapeutic strategies of intervention is still unclear. It has been suggested that carotid endarterectomy (CEA) improves cognitive functions, beyond the well-known preventive effect upon future stroke events. In the present study, we evaluated the beneficial effect of CEA in restoring mVCI. Among a large sample of subjects, who underwent CEA for severe carotid stenosis, two groups were identified according to the absence (CON) or the presence of cognitive impairment (mVCI). A multidimensional neuropsychological and behavioural assessment was performed in the week prior, and at a 3-month follow-up after CEA. The incidence of mVCI in this sample was 38%. Seventy-eight patients completed the follow-up (48 CON, 30 mVCI). Both groups showed a clinical improvement after CEA, although the effect was significantly higher in the mVCI group in regard to verbal memory (short story, p < 0.05), and attention (digit span, p < 0.05) scores. At follow-up, 60% of mVCI subjects were classified as having normal cognitive functions. Index of disease severity and peripheral arterial disease were found to be the predictors of improvement. These findings support that mVCI represents a heterogeneous, in some cases reversible condition. CEA might be considered a therapeutic option to treat and prevent cognitive decline in mVCI patients.
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http://dx.doi.org/10.1179/016164104225016245DOI Listing
July 2004

Abnormalities in the pattern of platelet amyloid precursor protein forms in patients with mild cognitive impairment and Alzheimer disease.

Arch Neurol 2002 Jan;59(1):71-5

Department of Neurology, University of Brescia, Piazza Ospedale 1, 25125, Brescia, Italy.

Context: Patients affected by sporadic Alzheimer disease (AD) show a significant alteration of amyloid precursor protein (APP) forms in platelets when compared with patients with dementia but without AD and age-matched controls.

Objective: To evaluate the ratio of platelet APP forms (APPr) in early-stage AD and mild cognitive impairment (MCI) and its potential as a biomarker for the early identification of AD.

Setting: Community population-based sample of patients admitted to 4 AD centers for investigation of cognitive disturbances.

Design And Methods: Thirty-five patients with mild AD (mAD), 21 patients with very mild AD (vmAD), 30 subjects with MCI, and 25 age-matched controls were included. The APPr was evaluated by Western blot analysis in platelet homogenate.

Results: Compared with controls (mean +/- SD, 0.93 +/- 0.3), the mean APPr was decreased in patients with mAD (0.44 +/- 0.24; P<.001) and patients with vmAD (0.49 +/- 0.3; P<.001). Regarding the MCI group, a significant decrease in APPr was found compared with controls (0.62 +/- 0.33; P<.001). Fixing a cutoff score of 0.6, sensitivity was 88.6% (31/35) for patients with mAD and 85.7% (18/21) for patients with vmAD, whereas specificity was 88% (22/25) for controls. Among patients with MCI, 18 (60%) of 30 individuals displayed APPr values below the cutoff.

Conclusions: Alteration of platelet APP forms is an early event in AD, and the measurement of APPr may be useful for the identification of preclinical AD in patients with MCI.
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http://dx.doi.org/10.1001/archneur.59.1.71DOI Listing
January 2002