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Authors: Lombardi, Gemma | Berti, Valentina | Ginestroni, Andrea | Nacmias, Benedetta | Sorbi, Sandro

Article Type: Case Report

Abstract: Amyloid-β deposition is the pathological hallmark of both cerebral amyloid angiopathy and Alzheimer’s disease dementia, clinical conditions that can share cognitive decline and positive Amyloid-PET scan. A case is reported involving an 82-year-old Italian female who presented initially a memory deficit, later transient focal neurologic episodes, and finally two symptomatic lobar intracerebral hemorrhages. In light of these events, MRI and PET imaging findings, acquired before cerebral hemorrhages, are reconsidered and discussed, highlighting the utility of Amyloid-PET in supporting an in vivo diagnosis of cerebral amyloid angiopathy.

Keywords: Alzheimer’s disease, amyloid PET, cerebral amyloid angiopathy, lobar cerebral hemorrhage, superficial siderosis, FDG-PET

DOI: 10.3233/ADR-230183

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 281-288, 2024

Authors: Lombardi, Gemma | Polito, Cristina | Berti, Valentina | Bagnoli, Silvia | Nacmias, Benedetta | Pupi, Alberto | Sorbi, Sandro

Article Type: Short Communication

Abstract: Bilingualism is an independent component of cognitive reserve that permits to delay dementia onset up to 5 years. We describe a case of a bilingual Italian man affected by mild cognitive impairment with high cognitive reserve that, despite the presence of multiple risk factors (ApoE ɛ 4/ɛ 4 genotype, older age, untreated Obstructive Sleep Apnea Syndrome, AD-like biomarker alterations) did not convert to Alzheimer’s disease up to 5 years follow-up. The present case confirms the role of bilingualism as a strong protective factor for dementia, even in the occurrence of multiple risk factors.

Keywords: Alzheimer’s disease, bilingualism, cognitive reserve, obstructive sleep apnea, prevention

DOI: 10.3233/JAD-180736

Citation: Journal of Alzheimer's Disease, vol. 66, no. 4, pp. 1389-1395, 2018

Authors: Mosconi, Lisa | Berti, Valentina | Glodzik, Lidia | Pupi, Alberto | De Santi, Susan | de Leon, Mony J.

Article Type: Review Article

Abstract: The development of prevention therapies for Alzheimer's disease (AD) would greatly benefit from biomarkers that are sensitive to subtle brain changes occurring in the preclinical stage of the disease. Early diagnostics is necessary to identify and treat at risk individuals before irreversible neuronal loss occurs. In vivo imaging has long been used to evaluate brain structural and functional abnormalities as predictors of future AD in non-demented persons. Prior to development of amyloid-β (Aβ) tracers for positron emission tomography (PET), the most widely utilized PET tracer in AD was 2-[18F]fluoro-2-Deoxy-D-glucose (FDG) PET. For over 20 years, FDG-PET has been used to …measure cerebral metabolic rates of glucose (CMRglc), a proxy for neuronal activity, in AD. Many studies have shown that CMRglc reductions occur early in AD, correlate with disease progression, and predict histopathological diagnosis. This paper reviews reports of clinical and preclinical CMRglc reductions observed in association with genetic and non-genetic risk factors for AD. We then briefly review brain Aβ PET imaging studies in AD and discuss the potential of combining symptoms-sensitive FDG-PET measures with pathology-specific Aβ-PET to improve the early detection of AD. Show more

Keywords: Amyloid-β, cerebral metabolic rate of glucose (CMRglc), normal aging, positron emission tomography, preclinical detection

DOI: 10.3233/JAD-2010-091504

Citation: Journal of Alzheimer's Disease, vol. 20, no. 3, pp. 843-854, 2010

Authors: Ferrari, Camilla | Polito, Cristina | Berti, Valentina | Lombardi, Gemma | Lucidi, Giulia | Bessi, Valentina | Bagnoli, Silvia | Piaceri, Irene | Nacmias, Benedetta | Sorbi, Sandro

Article Type: Research Article

Abstract: Background: Primary progressive aphasia (PPA) has been described as a neurodegenerative language disorder mainly affecting the left hemisphere. Few cases of right hemisphere damage in right-handed PPA subjects have been reported. This condition, named crossed aphasia in dextral (CAD), is relatively rare and probably related to an alteration during neurodevelopment of language networks. Objective: To explore the prevalence of CAD in an Italian cohort of 68 PPA patients, in order to evaluate whether right hemisphere language lateralization could be a risk factor for PPA. Methods: Clinical-demographic and cerebral [18 F]-fluorodeoxyglucose positron emission tomography ([18 F]FDG-PET) scan were analyzed, resulting in …23 logopenic variant (lvPPA) patients, 26 non-fluent variant (nfvPPA) patients, and 19 semantic variant (svPPA) patients. SPM single subject routine was performed for diagnostic purposes in order to identify the hypometabolic pattern of each patient. Based on brain metabolic profile, PPA patients were divided in right and left lvPPA, nfvPPA, and svPPA. [18 F]FDG-PET group analyses were performed with SPM two-sample t -test routine. Results: 26% of lvPPA cases were identified as CAD based on right hypometabolic pattern. CAD patients did not differ from left lvPPA regarding demographic features and general cognitive performance; however, they performed better in specific working memory tasks and showed brain hypometabolism limited to the superior, middle, and supramarginal temporal gyri. Conclusion: Atypical lateralization of language function could determine a vulnerability of the phonological language loop and in that way could be a risk factor for lvPPA. Show more

Keywords: Crossed-aphasia in dextral, dementia, language, lateralization, logopenic variant, primary progressive aphasia, risk factor

DOI: 10.3233/JAD-190677

Citation: Journal of Alzheimer's Disease, vol. 72, no. 4, pp. 1089-1096, 2019

Authors: Lombardi, Gemma | Berti, Valentina | Tedde, Andrea | Bagnoli, Silvia | Piaceri, Irene | Polito, Cristina | Lucidi, Giulia | Ferrari, Camilla | Ginestroni, Andrea | Moretti, Marco | Pupi, Alberto | Nacmias, Benedetta | Sorbi, Sandro

Article Type: Short Communication

Abstract: According to the literature, the APP Ala713Thr mutation is associated with Alzheimer’s disease and cerebral amyloid angiopathy. We describe a case of dementia clinically compatible with frontotemporal dementia in an APP Ala713Thr mutation carrier in which both [18 F]Florbetapir PET uptake and Aβ1-42 cerebrospinal fluid levels were normal. Further evidences are required to establish if this association is only incidental.

Keywords: APP Ala713Thr, familial Alzheimer’s disease, florbetapir PET, frontotemporal dementia

DOI: 10.3233/JAD-161170

Citation: Journal of Alzheimer's Disease, vol. 57, no. 3, pp. 697-703, 2017

Authors: Piaceri, Irene | Bessi, Valentina | Matà, Sabrina | Polito, Cristina | Tedde, Andrea | Berti, Valentina | Bagnoli, Silvia | Braccia, Arianna | Del Mastio, Monica | Pignone, Alberto Moggi | Pupi, Alberto | Sorbi, Sandro | Nacmias, Benedetta

Article Type: Short Communication

Abstract: A new risk gene associated with amyotrophic lateral sclerosis (ALS) has recently been identified: the Tank-binding kinase 1 (TBK1 ) gene. Up to now, 90 TBK1 variants have been described in ALS patients with or without frontotemporal dementia (FTD), thus making TBK1 the third or fourth most frequent genetic cause of ALS and FTD. A point mutation analysis in a cohort of 69 Italian ALS patients was performed in order to analyze the frequency of TBK1 mutations and the correlation with clinical phenotypes. The analysis identified the novel variant p.Tyr424Asp in a patient with a rapid progression of the disease. …Our data supports the implication of TBK1 in ALS pathogenesis in Italy. Show more

Keywords: Amyotrophic lateral sclerosis, genetics, Italy, missense mutation

DOI: 10.3233/JAD-170694

Citation: Journal of Alzheimer's Disease, vol. 61, no. 1, pp. 41-46, 2018

Authors: Ferrari, Camilla | Lombardi, Gemma | Polito, Cristina | Lucidi, Giulia | Bagnoli, Silvia | Piaceri, Irene | Nacmias, Benedetta | Berti, Valentina | Rizzuto, Debora | Fratiglioni, Laura | Sorbi, Sandro

Article Type: Research Article

Abstract: Background: Alzheimer’s disease (AD) patients present high variability in the rate of cognitive decline. Despite the wide knowledge on factors influencing dementia risk, little is known on what accounts for AD progression. Previous studies on this topic have mainly analyzed each factor separately without taking into account the interaction between genetic and non-genetic factors. Objective: The aim of the present study is to evaluate the role of demographic, clinical, therapeutic, and genetic factors and their interaction on cognitive decline among newly diagnosed AD patients. Methods: We retrospectively selected 160 AD patients diagnosed at the Neurology Unit of Careggi University Hospital …of Florence. We evaluated the occurrence of rapid cognitive changes defined as the worsening of more than four points at the Mini-Mental State Examination after 2-year follow up period. Results: Among the 160 AD patients, 50% presented rapid disease progression. Extrapyramidal signs at disease onset were predictors of worse outcome (OR 2.2), especially among Apolipoprotein E (APOE) ɛ 4 allele carriers, while the presence of family history for dementia decreased the risk of rapid progression by about 50%. Higher educated ɛ 4-carriers showed a slower AD progression. We identified the chronic use of aspirin as potential secondary preventative strategy for the non ɛ 4-carriers. Conclusion: At dementia onset, some clinical and demographic data can be predictors of future progression. The outcomes of the present study support the already hypothesized interaction between genetic and non-genetic factors during disease course and suggest genetic-based approaches. Show more

Keywords: Alzheimer’s disease, APOE, aspirin, decline, dementia, progression, risk factors

DOI: 10.3233/JAD-170665

Citation: Journal of Alzheimer's Disease, vol. 61, no. 2, pp. 785-791, 2018

Authors: Lombardi, Gemma | Pupi, Alberto | Bessi, Valentina | Polito, Cristina | Padiglioni, Sonia | Ferrari, Camilla | Lucidi, Giulia | Berti, Valentina | De Cristofaro, Maria Teresa | Piaceri, Irene | Bagnoli, Silvia | Nacmias, Benedetta | Sorbi, Sandro

Article Type: Research Article

Abstract: Background: Discordance among amyloid biomarkers is a challenge to overcome in order to increase diagnostic accuracy in dementia. Objectives: 1) To verify that cerebrospinal fluid (CSF) Aβ42 /Aβ40 ratio (AβR) better agrees with Amyloid PET (Amy-PET) results compared to CSF Aβ42 ; 2) to detect differences among concordant positive, concordant negative, and discordant cases, basing the concordance definition on the agreement between CSF AβR and Amy-PET results; 3) to define the suspected underlying pathology of discordant cases using in vivo biomarkers. Method: We retrospectively enrolled 39 cognitively impaired participants in which neuropsychological tests, apolipoprotein E genotype determination, TC/MRI, FDG-PET, Amy-PET, …and CSF analysis had been performed. In all cases, CSF analysis was repeated using the automated Lumipulse method. In discordant cases, FDG-PET scans were evaluated visually and using automated classifiers. Results: CSF AβR better agreed with Amy-PET compared to CSF Aβ42 (Cohen’s K 0.431 versus 0.05). Comparisons among groups did not show any difference in clinical characteristics except for age at symptoms onset that was higher in the 6 discordant cases with abnormal CSF AβR values and negative Amy-PET (CSF AβR+/AmyPET–). FDG-PET and all CSF markers (Aβ42 , AβR, p-Tau, t-Tau) were suggestive of Alzheimer’s disease (AD) in 5 of these 6 cases. Conclusion: 1) CSF AβR is the CSF amyloid marker that shows the better level of agreement with Amy-PET results; 2) The use of FDG-PET and CSF-Tau markers in CSFAβR+/Amy-PET–discordant cases can support AD diagnosis; 3) Disagreement between positive CSF AβR and negative Amy-PET in symptomatic aged AD patients could be due to the variability in plaques conformation and a negative Amy-PET scan cannot be always sufficient to rule out AD. Show more

Keywords: Aging, Alzheimer’s disease, amyloid, biomarkers, cerebrospinal fluid, diagnosis, PET scan

DOI: 10.3233/JAD-200119

Citation: Journal of Alzheimer's Disease, vol. 77, no. 1, pp. 203-217, 2020