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Articles by Giovanni B. Frisoni
Total Records ( 6 ) for Giovanni B. Frisoni
  Giovanni B. Frisoni , Annapaola Prestia , Giovanni B. Frisoni , Samantha Galluzzi , Melissa Romano , Maria Cotelli , Massimo Gennarelli , Giuliano Binetti , Luisella Bocchio , Barbara Paghera , Giovanni Amicucci , Matteo Bonetti , Luisa Benussi , Roberta Ghidoni and Cristina Geroldi
  Background New marker-based criteria for the diagnosis of Alzheimer's disease (AD) were recently proposed. We describe their operational translation in 144 consecutive patients referred to our Memory Clinic. Methods Visual ratings of hippocampal atrophy and of cortical glucose hypometabolism in magnetic resonance imaging and positron emission tomography, and concentrations of total tau and Aβ1-42 in cerebrospinal fluid were assessed in 12 patients with subjective memory complaints (SMCs) (Mini-Mental State Examination [MMSE] score, 28.0 ± 1.1 [mean ± SD]), 37 with mild cognitive impairment (MCI) (MMSE, 25.1 ± 3.6), 55 with AD (MMSE, 21.1 ± 3.5), and 40 with non-AD dementia (MMSE, 21.6 ± 5.5). Results The sensitivity for AD of each individual biomarker was higher (65% to 87%) than for MCI (18% to 50%). Each biomarker's specificity for SMC and non-AD dementias was good to moderate (83% and 53%). Positivity for at least one marker increased the probability 38 times of belonging to the AD group (P < 0.0001). Conclusion The new diagnostic criteria can be operationalized in clinical routines, but longitudinal studies of MCI patients will need to assess the criteria's prognostic value.
  Giovanni B. Frisoni and Clifford R. Jack
  Hippocampal atrophy is a marker of disease state and progression in Alzheimer‘s disease. The gold standard to measure hippocampal volume is through manual segmentation. A number of protocols to measure hippocampal volume through manual segmentation have been developed, but the marked heterogeneity of anatomical landmarks has given rise to wide variability of volume estimates. With the aim of fostering the use of hippocampal volume in routine clinical settings, an international task force is currently working on developing a harmonized protocol that will resolve and reduce the present heterogeneity. The task force will then validate the harmonized protocol, develop harmonized probabilistic hippocampal maps, and develop illustrative and educational material on the use of the harmonized protocol and maps.
  Niklas Mattsson , Ulf Andreasson , Staffan Persson , Hiroyuki Arai , Sat Dev Batish , Sergio Bernardini , Luisella Bocchio- Chiavetto , Marinus A. Blankenstein , Maria C. Carrillo , Sonia Chalbot , Els Coart , Davide Chiasserini , Neal Cutler , Gunilla Dahlfors , Stefan Duller , Anne M. Fagan , Orestes Forlenza , Giovanni B. Frisoni , Douglas Galasko , Daniela Galimberti , Harald Hampel , Aase Handberg , Michael T. Heneka , Adrianna Z. Herskovits , Sanna-Kaisa Herukka , David M. Holtzman , Christian Humpel , Bradley T. Hyman , Khalid Iqbal , Khalid Iqbal , Stephan A. Kaeser , Elmar Kaiser , Elisabeth Kapaki , Daniel Kidd , Peter Klivenyi , Cindy S. Knudsen , Markus P. Kummer , James Lui , Albert Llado , Piotr Lewczuk , Qiao-Xin Li , Ralph Martins , Colin Masters , John McAuliffe , Marc Mercken , Abhay Moghekar , Jose Luis Molinuevo , Thomas J. Montine , William Nowatzke , Richard O’Brien , Markus Otto , George P. Paraskevas , Lucilla Parnetti , Ronald C. Petersen , David Prvulovic , Herman P.M. de Reus , Robert A. Rissman , Elio Scarpini , Alessandro Stefani , Hilkka Soininen , Johannes Schroder , Leslie M. Shaw , Anders Skinningsrud , Brith Skrogstad and Annette Spreer
  Background The cerebrospinal fluid (CSF) biomarkers amyloid β (Aβ)-42, total-tau (T-tau), and phosphorylated-tau (P-tau) demonstrate good diagnostic accuracy for Alzheimer‘s disease (AD). However, there are large variations in biomarker measurements between studies, and between and within laboratories. The Alzheimer‘s Association has initiated a global quality control program to estimate and monitor variability of measurements, quantify batch-to-batch assay variations, and identify sources of variability. In this article, we present the results from the first two rounds of the program. Methods The program is open for laboratories using commercially available kits for Aβ, T-tau, or P-tau. CSF samples (aliquots of pooled CSF) are sent for analysis several times a year from the Clinical Neurochemistry Laboratory at the Molndal campus of the University of Gothenburg, Sweden. Each round consists of three quality control samples. Results Forty laboratories participated. Twenty-six used INNOTEST enzyme-linked immunosorbent assay kits, 14 used Luminex xMAP with the INNO-BIA AlzBio3 kit (both measure Aβ-(1-42), P-tau(181P), and T-tau), and 5 used Meso Scale Discovery with the Aβ triplex (AβN-42, AβN-40, and AβN-38) or T-tau kits. The total coefficients of variation between the laboratories were 13% to 36%. Five laboratories analyzed the samples six times on different occasions. Within-laboratory precisions differed considerably between biomarkers within individual laboratories. Conclusions Measurements of CSF AD biomarkers show large between-laboratory variability, likely caused by factors related to analytical procedures and the analytical kits. Standardization of laboratory procedures and efforts by kit vendors to increase kit performance might lower variability, and will likely increase the usefulness of CSF AD biomarkers.
  Clifford R. Jack , Frederik Barkhof , Matt A. Bernstein , Marc Cantillon , Patricia E. Cole , Charles DeCarli , Bruno Dubois , Simon Duchesne , Nick C. Fox , Giovanni B. Frisoni , Harald Hampel , Derek L.G. Hill , Keith Johnson , Jean-Francois Mangin , Philip Scheltens , Adam J. Schwarz , Reisa Sperling , Joyce Suhy , Paul M. Thompson , Michael Weiner and Norman L. Foster
  Background The promise of Alzheimer‘s disease biomarkers has led to their incorporation in new diagnostic criteria and in therapeutic trials; however, significant barriers exist to widespread use. Chief among these is the lack of internationally accepted standards for quantitative metrics. Hippocampal volumetry is the most widely studied quantitative magnetic resonance imaging measure in Alzheimer‘s disease and thus represents the most rational target for an initial effort at standardization. Methods and Results The authors of this position paper propose a path toward this goal. The steps include the following: (1) Establish and empower an oversight board to manage and assess the effort, (2) adopt the standardized definition of anatomic hippocampal boundaries on magnetic resonance imaging arising from the European Alzheimer‘s Disease Centers–Alzheimer‘s Disease Neuroimaging Initiative hippocampal harmonization effort as a reference standard, (3) establish a scientifically appropriate, publicly available reference standard data set based on manual delineation of the hippocampus in an appropriate sample of subjects (Alzheimer‘s Disease Neuroimaging Initiative), and (4) define minimum technical and prognostic performance metrics for validation of new measurement techniques using the reference standard data set as a benchmark. Conclusions Although manual delineation of the hippocampus is the best available reference standard, practical application of hippocampal volumetry will require automated methods. Our intent was to establish a mechanism for credentialing automated software applications to achieve internationally recognized accuracy and prognostic performance standards that lead to the systematic evaluation and then widespread acceptance and use of hippocampal volumetry. The standardization and assay validation process outlined for hippocampal volumetry was envisioned as a template that could be applied to other imaging biomarkers.
  Maria C. Carrillo , Lisa J. Bain , Giovanni B. Frisoni and Michael W. Weiner
  The Alzheimer‘s Disease Neuroimaging Initiative (ADNI) was launched in 2003 to speed drug development by validating imaging and blood/cerebrospinal fluid biomarkers for Alzheimer‘s disease clinical treatment trials. ADNI is a naturalistic (nontreatment) multisite longitudinal study. A true public–private partnership, the first phase of ADNI (ADNI 1) set a new standard for data sharing without embargo. In addition, it has been extended to 2017 by additional funding (North American-ADNI Grand Opportunities and ADNI 2) as well as multiple projects around the world, collectively known as Worldwide ADNI (WW-ADNI). The goal of WW-ADNI is to harmonize projects and results across different geographical sites and to encourage and harmonize data management and availability to investigators around the world. WW-ADNI projects are currently underway in North America, Europe, Japan, Australia, Korea, Taiwan, and Argentina, with a nascent program in China and a possible future program in Brazil.
  Donata Paternico , Samantha Galluzzi , Valeria Drago , Luisella Bocchio- Chiavetto , Roberta Zanardini , Laura Pedrini , Manuela Baronio , Giovanni Amicucci and Giovanni B. Frisoni
  Background Low amyloid β42 (Aβ42) and high total tau and phosphorylated tau (p-tau) concentrations in the cerebrospinal fluid (CSF) are biomarkers of Alzheimer‘s disease (AD), reflecting brain deposition of amyloid plaques and tangles. Age and apolipoprotein E allele E4 are two strong risk factors for AD, but few data are still available on their effect on CSF markers in normal aging. Objective To study the effect of age on CSF Aβ42, total tau, and p-tau levels in a well-characterized group of cognitively normal subjects. Methods CSF Aβ42 levels of 81 subjects (27% female, 53 ± 15.3 years, range: 21–88) were determined with sandwich enzyme-linked immunosorbent assay; of these, total tau and p-tau levels were measured in 61 (75%) and 42 (52%) cases, respectively. A linear regression analysis between age and CSF markers was carried out on the whole sample and separately in apolipoprotein E allele ɛ4 carriers and noncarriers. Results The median levels of all markers were significantly different between young (<65 years) and old (≥65 years) subjects (Aβ42: P = .03; tau: P = .02; p-tau: P = .002; tau/Aβ42: P = .004; p-tau/Aβ42: P = .03). The association of marker levels with age was confirmed in linear regression models, where a positive relationship with age was observed for total tau (B = 2.3; 95% confidence interval [CI]: 0.89 to 3.7; P = .002), p-tau (B = 0.5; 95% CI: 0.1 to 0.9; P = .02), and tau/Aβ42 ratio (B = 0.006; 95% CI: 0.002 to 0.01; P = .002). No subjects showed abnormal tau, whereas 19% showed abnormal CSF Aβ42 concentrations. Conclusion In cognitively normal subjects, the concentrations of CSF biomarkers of AD are associated with age. Further longitudinal studies could clarify whether Aβ42 low levels represent a preclinical AD biomarker.
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