Genetic Counseling and Testing for Alzheimer’s Disease and Frontotemporal Lobar Degeneration: An Italian Consensus Protocol

Article type: Research Article

Authors: Bocchetta, Martina^{a; b} | Mega, Anna^a | Bernardi, Livia^c | Di Maria, Emilio^d | Benussi, Luisa^e | Binetti, Giuliano^f | Borroni, Barbara^g | Colao, Rosanna^c | Di Fede, Giuseppe^h | Fostinelli, Silvia^e | Galimberti, Danielaⁱ | Gennarelli, Massimo^j | Ghidoni, Roberta^e | Piaceri, Irene^k | Pievani, Michela^a | Porteri, Corinna^l | Redaelli, Veronica^h | Rossi, Giacomina^h | Suardi, Silvia^h | Babiloni, Claudio^m | Scarpini, Elioⁱ | Tagliavini, Fabrizio^h | Padovani, Alessandro^g | Nacmias, Benedetta^k | Sorbi, Sandro^k | Frisoni, Giovanni B.^{a; n} | Bruni, Amalia C.^{c; *} | SINdem

Collaborators: Bozzali, Marco^o | Parnetti, Lucilla^p | Ferrarese, Carlo^q | Cappa, Stefano F.^r | Marra, Camillo^s | Masullo, Carlo^t | Rainero, Innocenzo^u | Silani, Vincenzo^v | Sorrentino, Giuseppe^w | Bruno, Giuseppe^x | Cagnin, Annachiara^y

Affiliations: [a] Laboratory of Alzheimer’s Neuroimaging and Epidemiology, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy | [b] Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy | [c] Centro Regionale di Neurogenetica, ASP Catanzaro, Lamezia terme (CZ) Italy | [d] Department of Health Sciences, University of Genova and Division of Medical Genetics, Galliera Hospital, Genova, Italy | [e] Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy | [f] IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy | [g] University of Brescia and Centre for Ageing Brain and Neurodegenerative Disorders, Neurology Unit, Brescia, Brescia, Italy | [h] IRCCS Fondazione Istituto Neurologico Carlo Besta, Milan, Italy | [i] University of Milan, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy | [j] Genetic Unit, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy | [k] Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy | [l] Bioethics Unit, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy | [m] Departiment of Physiology and Pharmacology, University of Rome “La Sapienza”, Rome, Italy; IRCCS San Raffaele Pisana of Rome, Italy | [n] Memory Clinic and LANVIE - Laboratory of Neuroimaging of Aging, University Hospitals and University of Geneva, Geneva, Switzerland | [o] Neuroimaging Laboratory, IRCCS Santa Lucia Foundation, Rome, Italy | [p] Section of Neurology, Department of Medicine, Centre for Memory Disturbances, University of Perugia, Perugia, Italy | [q] School of Medicine and Surgery, Milan Center for Neuroscience (NeuroMI), University of Milano Bicocca, Italy; Neurology Unit, San Gerardo Hospital, Monza, Italy | [r] NeTS Center-Istituto Universitario di Studi Superiori (IUSS), Pavia, Italy | [s] Institute of Neurology and Center for Neuropsychological Research of the Policlinico Gemelli, Catholic University of Rome, Italy | [t] Department of Neuroscience, Institutes of Neurology, Catholic University of the Sacred Heart, Rome, Italy | [u] Neurology I - Headache Center, Department of Neuroscience “Rita Levi Montalcini, University of Torino, Torino, Italy | [v] Department of Neurology-Stroke Unit and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, “Dino Ferrari” Centre, Department of Pathophysiology and Transplantation, Universita’ degli Studi di Milano, Milan, Italy | [w] University of Naples Parthenope, Naples, Italy | [x] Memory Clinic, Department of Neurology and Psychiatry, University of Rome “Sapienza”, Italy | [y] Department of Neurosciences (DNS), University of Padova, Padua; IRCCS, San Camillo Hospital Foundation, Venice, Italy

Correspondence: [*] Correspondence to: Amalia Cecilia Bruni, MD; Centro Regionale di Neurogenetica, Viale Arturo Perugini, 88046 Lamezia Terme, Italy; Tel.: +39 0968 208080; Fax: +39 0968 208032; E-mail: [email protected].

Abstract: Background:Genetic testing of familial Alzheimer’s disease (AD) and frontotemporal lobar degeneration (FTLD) is attracting interest thanks to innovative primary prevention clinical trials and increased request for information by at-risk individuals. However, ethical, social, and psychological implications are paramount and genetic testing must be supported by structured genetic counseling. In Italy, practice parameters and guidelines for genetic counseling in dementia are not available. Objective:To develop a nationally harmonized protocol for genetic counseling and testing of familial AD and FTLD. Methods:Activities were carried out in the context of the Italian Dominantly Inherited Alzheimer’s and Frontotemporal Network (IT-DIAfN) project, a national network of centers of excellence with expertise in managing patients with familial AD and FTLD. A survey of the literature on genetic counseling protocols and guidelines was conducted. Local protocols for genetic counseling were surveyed. Differences and commonalities among protocols were identified and discussed among project partners. Consensus was reached following implicit aggregation methods. Results:Consensus was reached on a protocol for patients with clinically diagnosed familial AD or FTLD and a distinct protocol for their at-risk relatives. Genetic counseling should be provided by a multidisciplinary team including a geneticist, a neurologist/geriatrician, and a psychologist/psychiatrist, according to the following schedule: (i) initial consultation with tailored information on the genetics of the dementias; (ii) clinical, psychological, and cognitive assessment; if deemed appropriate (iii) genetic testing following a structured decision tree for gene mutation search; (iv) genetic testing result disclosure; (v) psychological support follow-up. Conclusion:This genetic counseling protocol provides Italian centers with a line of shared practice for dealing with the requests for genetic testing for familial AD and FTLD from patients and at-risk relatives, who may also be eligible participants for novel prevention clinical trials.

Keywords: Alzheimer’s disease, frontotemporal degeneration, genetic counseling, genetic testing

DOI: 10.3233/JAD-150849

Journal: Journal of Alzheimer's Disease, vol. 51, no. 1, pp. 277-291, 2016