ORCID Profile
0000-0003-0729-5246
Current Organisations
Karolinska Institute
,
Azienda Ospedaliera di Perugia
,
Karolinska Institutet
,
Università degli studi di Perugia
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Publisher: Springer Science and Business Media LLC
Date: 27-10-2013
DOI: 10.1038/NG.2802
Publisher: Springer Science and Business Media LLC
Date: 02-2016
DOI: 10.1038/NN.4228
Publisher: Springer Science and Business Media LLC
Date: 03-10-2016
DOI: 10.1038/NN.4398
Publisher: Springer Science and Business Media LLC
Date: 17-07-2017
DOI: 10.1038/NG.3916
Publisher: Elsevier BV
Date: 02-2014
Publisher: Public Library of Science (PLoS)
Date: 12-06-2014
Publisher: Springer Science and Business Media LLC
Date: 18-01-2017
DOI: 10.1038/NCOMMS13624
Abstract: The hippoc al formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippoc al volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippoc al structure here we perform a genome-wide association study (GWAS) of 33,536 in iduals and discover six independent loci significantly associated with hippoc al volume, four of them novel. Of the novel loci, three lie within genes ( ASTN2 , DPP4 and MAST4 ) and one is found 200 kb upstream of SHH . A hippoc al subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippoc al volume are also associated with increased risk for Alzheimer’s disease ( r g =−0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippoc al volume and risk for neuropsychiatric illness.
Publisher: Springer Science and Business Media LLC
Date: 05-11-2014
Publisher: Wiley
Date: 19-10-2017
DOI: 10.1016/J.JALZ.2017.09.007
Abstract: Progress in understanding and management of vascular cognitive impairment (VCI) has been h ered by lack of consensus on diagnosis, reflecting the use of multiple different assessment protocols. A large multinational group of clinicians and researchers participated in a two-phase Vascular Impairment of Cognition Classification Consensus Study (VICCCS) to agree on principles (VICCCS-1) and protocols (VICCCS-2) for diagnosis of VCI. We present VICCCS-2. We used VICCCS-1 principles and published diagnostic guidelines as points of reference for an online Delphi survey aimed at achieving consensus on clinical diagnosis of VCI. Six survey rounds comprising 65-79 participants agreed guidelines for diagnosis of VICCCS-revised mild and major forms of VCI and endorsed the National Institute of Neurological Disorders-Canadian Stroke Network neuropsychological assessment protocols and recommendations for imaging. The VICCCS-2 suggests standardized use of the National Institute of Neurological Disorders-Canadian Stroke Network recommendations on neuropsychological and imaging assessment for diagnosis of VCI so as to promote research collaboration.
Publisher: Elsevier BV
Date: 12-2014
DOI: 10.1016/J.NEUROBIOLAGING.2014.07.023
Abstract: Although epidemiological studies suggest that type 2 diabetes mellitus (T2DM) increases the risk of late-onset Alzheimer's disease (LOAD), the biological basis of this relationship is not well understood. The aim of this study was to examine the genetic comorbidity between the 2 disorders and to investigate whether genetic liability to T2DM, estimated by a genotype risk scores based on T2DM associated loci, is associated with increased risk of LOAD. This study was performed in 2 stages. In stage 1, we combined genotypes for the top 15 T2DM-associated polymorphisms drawn from approximately 3000 in iduals (1349 cases and 1351 control subjects) with extracted and/or imputed data from 6 genome-wide studies (>10,000 in iduals 4507 cases, 2183 controls, 4989 population controls) to form a genotype risk score and examined if this was associated with increased LOAD risk in a combined meta-analysis. In stage 2, we investigated the association of LOAD with an expanded T2DM score made of 45 well-established variants drawn from the 6 genome-wide studies. Results were combined in a meta-analysis. Both stage 1 and stage 2 T2DM risk scores were not associated with LOAD risk (odds ratio = 0.988 95% confidence interval, 0.972-1.004 p = 0.144 and odds ratio = 0.993 95% confidence interval, 0.983-1.003 p = 0.149 per allele, respectively). Contrary to expectation, genotype risk scores based on established T2DM candidates were not associated with increased risk of LOAD. The observed epidemiological associations between T2DM and LOAD could therefore be a consequence of secondary disease processes, pleiotropic mechanisms, and/or common environmental risk factors. Future work should focus on well-characterized longitudinal cohorts with extensive phenotypic and genetic data relevant to both LOAD and T2DM.
Publisher: Wiley
Date: 19-12-2014
Publisher: Wiley
Date: 30-03-2016
DOI: 10.1002/ANA.24621
Publisher: Elsevier BV
Date: 08-2012
DOI: 10.1016/J.NEUROBIOLAGING.2011.12.036
Abstract: Alzheimer's disease (AD) and age-related macular degeneration (AMD) are both neurodegenerative disorders which share common pathological and biochemical features of the complement pathway. The aim of this study was to investigate whether there is an association between well replicated AMD genetic risk factors and AD. A large cohort of AD (n = 3898) patients and controls were genotyped for single nucleotide polymorphisms (SNPs) in the complement factor H (CFH), the Age-related maculopathy susceptibility protein 2 (ARMS2) the complement component 2 (C2), the complement factor B (CFB), and the complement component 3 (C3) genes. While significant but modest associations were identified between the complement factor H, the age-related maculopathy susceptibility protein 2, and the complement component 3 single nucleotide polymorphisms and AD, these were different in direction or genetic model to that observed in AMD. In addition the multilocus genetic model that predicts around a half of the sibling risk for AMD does not predict risk for AD. Our study provides further support to the hypothesis that while activation of the alternative complement pathway is central to AMD pathogenesis, it is less involved in AD.
Publisher: Springer Science and Business Media LLC
Date: 21-01-2015
DOI: 10.1038/NATURE14101
Publisher: Elsevier BV
Date: 04-2016
Publisher: Wiley
Date: 10-12-2016
DOI: 10.1016/J.JALZ.2016.10.007
Abstract: Numerous diagnostic criteria have tried to tackle the variability in clinical manifestations and problematic diagnosis of vascular cognitive impairment (VCI) but none have been universally accepted. These criteria have not been readily comparable, impacting on clinical diagnosis rates and in turn prevalence estimates, research, and treatment. The Vascular Impairment of Cognition Classification Consensus Study (VICCCS) involved participants (81% academic researchers) from 27 countries in an online Delphi consensus study. Participants reviewed previously proposed concepts to develop new guidelines. VICCCS had a mean of 122 (98-153) respondents across the study and a 67% threshold to represent consensus. VICCCS redefined VCI including classification of mild and major forms of VCI and subtypes. It proposes new standardized VCI-associated terminology and future research priorities to address gaps in current knowledge. VICCCS proposes a consensus-based updated conceptualization of VCI intended to facilitate standardization in research.
Publisher: Wiley
Date: 28-09-2016
DOI: 10.1016/J.JALZ.2016.08.003
Abstract: The aim of this study was to (1) replicate previous associations between six blood lipids and Alzheimer's disease (AD) (Proitsi et al 2015) and (2) identify novel associations between lipids, clinical AD diagnosis, disease progression and brain atrophy (left/right hippoc us/entorhinal cortex). We performed untargeted lipidomic analysis on 148 AD and 152 elderly control plasma s les and used univariate and multivariate analysis methods. We replicated our previous lipids associations and reported novel associations between lipids molecules and all phenotypes. A combination of 24 molecules classified AD patients with >70% accuracy in a test and a validation data set, and we identified lipid signatures that predicted disease progression (R Blood lipids are promising AD biomarkers that may lead to new treatment strategies.
Publisher: Springer Science and Business Media LLC
Date: 13-01-2015
DOI: 10.1038/TP.2014.127
Abstract: There is an urgent need for the identification of Alzheimer’s disease (AD) biomarkers. Studies have now suggested the promising use of associations with blood metabolites as functional intermediate phenotypes in biomedical and pharmaceutical research. The aim of this study was to use lipidomics to identify a battery of plasma metabolite molecules that could predict AD patients from controls. We performed a comprehensive untargeted lipidomic analysis, using ultra-performance liquid chromatography/mass spectrometry on plasma s les from 35 AD patients, 40 elderly controls and 48 in iduals with mild cognitive impairment (MCI) and used multivariate analysis methods to identify metabolites associated with AD status. A combination of 10 metabolites could discriminate AD patients from controls with 79.2% accuracy (81.8% sensitivity, 76.9% specificity and an area under curve of 0.792) in a novel test set. Six of the metabolites were identified as long chain cholesteryl esters (ChEs) and were reduced in AD (ChE 32:0, odds ratio (OR)=0.237, 95% confidence interval (CI)=0.10–0.48, P =4.19E−04 ChE 34:0, OR=0.152, 95% CI=0.05–0.37, P =2.90E−04 ChE 34:6, OR=0.126, 95% CI=0.03–0.35, P =5.40E−04 ChE 32:4, OR=0.056, 95% CI=0.01–0.24, P =6.56E−04 and ChE 33:6, OR=0.205, 95% CI=0.06–0.50, P =2.21E−03, per (log2) metabolite unit). The levels of these metabolites followed the trend control MCI AD. We, additionally, found no association between cholesterol, the precursor of ChE and AD. This study identified new ChE molecules, involved in cholesterol metabolism, implicated in AD, which may help identify new therapeutic targets although, these findings need to be replicated in larger well-phenotyped cohorts.
Publisher: S. Karger AG
Date: 2011
DOI: 10.1159/000334657
Abstract: i Aims: /i The main aims of the study were the translation and the subsequent validation in Italian of the Addenbrooke’s Cognitive Examination Revised (ACE-R), and the evaluation of its usefulness in discriminating cognitively normal subjects from patients with mild dementia in an elderly population. i Methods: /i The ACE-R was translated and adapted into Italian. The Italian ACE-R was administered to a group of 179 elderly subjects (72 cognitively healthy and 107 subjects with mild dementia, mean age 75.4 ± 6.4 years). The group was stratified into two subs les according to age, i.e. a young-old ( years) and an old-old (≧75 years) group, in order to evaluate the sensitivity and specificity of the test in detecting dementia in different age strata of elderly subjects. i Results: /i The reliability of the Italian ACE-R was extremely good (α-coefficient = 0.85). Two different cutoffs were identified for young-old (cutoff 79 sensitivity 90% and specificity 80%) and old-old subjects (cutoff 60 sensitivity 82% and specificity 100%). i Conclusions: /i The Italian ACE-R is a valid screening tool to detect dementia, especially in the old-old population, which represents not only the fastest growing age group but also the group at the highest risk of dementia in Western countries.
No related grants have been discovered for Patrizia Mecocci.