title: Association between CSF biomarkers, hippocampal volume and cognitive function in patients with amnestic mild cognitive impairment (MCI).
abstract: Few studies have examined the relationship between CSF and structural biomarkers, and cognitive function in MCI. We examined the relationship between cognitive function, hippocampal volume and cerebrospinal fluid (CSF) Aβ42and tau in 145 patients with MCI. Patients were assessed on cognitive tasks from the Cambridge Neuropsychological Test Automated Battery (CANTAB), the Geriatric Depression Scale and the Functional Activities Questionnaire. Hippocampal volume was measured using magnetic resonance imaging (MRI), and CSF markers of Aβ42, tau and p-tau181were also measured. Worse performance on a wide range of memory and sustained attention tasks were associated with reduced hippocampal volume, higher CSF tau and p-tau181and increased tau/Aβ42ratio. Memory tasks were also associated with lower ability to conduct functional activities of daily living, providing a link between AD biomarkers, memory performance and functional outcome. These results suggest that biomarkers of Aβ and tau are strongly related to cognitive performance as assessed by the CANTAB, and have implications for the early detection and characterization of incipient AD.
authors.affiliation: Heptares Therapeutics Ltd, Cambridge, UK; Brain Mapping Unit, Department of Psychiatry, University of Cambridge, Cambridge, UK. Electronic address: pradeep.nathan@heptares.com.
authors.forename: Pradeep J
authors.initials: PJ
authors.lastname: Nathan
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Melbourne, Victoria, Australia. Electronic address: yen.lim@florey.edu.au.
authors.forename: Yen Ying
authors.initials: YY
authors.lastname: Lim
authors.affiliation: Cambridge Cognition, Cambridge, UK.
authors.forename: Rosemary
authors.initials: R
authors.lastname: Abbott
authors.affiliation: Lab Alzheimer's Neuroimaging & Epidemiology, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.
authors.forename: Samantha
authors.initials: S
authors.lastname: Galluzzi
authors.affiliation: Lab Alzheimer's Neuroimaging & Epidemiology, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.
authors.forename: Moira
authors.initials: M
authors.lastname: Marizzoni
authors.affiliation: Department of Physiology and Pharmacology, University of Rome "La Sapienza", Rome, Italy; IRCCS San Raffaele Pisana of Rome, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Babiloni
authors.affiliation: Department of Neuroscience, Mario Negri Institute for Pharmacological Research, Milano, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Albani
authors.affiliation: Department of Psychiatry and Clinical Psychobiology, Faculty of Medicine, University of Barcelona and Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalunya, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Bartres-Faz
authors.affiliation: Aix-Marseille Université, INSERM, INS UMR_S 1106, Marseille, France; Service de Neurologie et Neuropsychologie, APHM Hôpital Timone Adultes, Marseille, France.
authors.forename: Mira
authors.initials: M
authors.lastname: Didic
authors.affiliation: Clinica Neurologica, Centro Disturbi della Memoria, Università di Perugia, Ospedale Santa Maria della Misericordia, Perugia, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Farotti
authors.affiliation: Clinica Neurologica, Centro Disturbi della Memoria, Università di Perugia, Ospedale Santa Maria della Misericordia, Perugia, Italy.
authors.forename: Lucilla
authors.initials: L
authors.lastname: Parnetti
authors.affiliation: Clinica Neurologica, Centro Disturbi della Memoria, Università di Perugia, Ospedale Santa Maria della Misericordia, Perugia, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Salvadori
authors.affiliation: Department of Psychiatry and Psychotherapy, LVR-Hospital Essen, Faculty of Medicine, University of Duisburg-Essen, Essen, Germany.
authors.forename: Bernhard W
authors.initials: BW
authors.lastname: Müller
authors.affiliation: Department of Neuroscience, Mario Negri Institute for Pharmacological Research, Milano, Italy.
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Forloni
authors.affiliation: Department of Neuroscience (DINOGMI), Clinical Neurology, University of Genoa, Genoa, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Girtler
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Leipzig, Leipzig, Germany.
authors.forename: Tilman
authors.initials: T
authors.lastname: Hensch
authors.affiliation: Center for Mind/Brain Sciences, University of Trento, Rovereto, Trento, Italy.
authors.forename: Jorge
authors.initials: J
authors.lastname: Jovicich
authors.affiliation: Department of Neurology, Alzheimer Centre, VU Medical Centre, Amsterdam, the Netherlands.
authors.forename: Annebet
authors.initials: A
authors.lastname: Leeuwis
authors.affiliation: Department of Gerontology, Neurosciences and Orthopedics, Institute of Neurology, Catholic University, Policlinic A. Gemelli Foundation, Rome, Italy.
authors.forename: Camillo
authors.initials: C
authors.lastname: Marra
authors.affiliation: Alzheimer's Disease Unit and Other Cognitive Disorders Unit, Hospital Clínic de Barcelona, and Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalunya, Spain.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Molinuevo
authors.affiliation: Department of Neuroscience (DINOGMI), Clinical Neurology, University of Genoa, Genoa, Italy.
authors.forename: Flavio
authors.initials: F
authors.lastname: Nobili
authors.affiliation: INSERM, Imagerie cérébrale et handicaps neurologiques UMR 825, Toulouse, France.
authors.forename: Jeremie
authors.initials: J
authors.lastname: Pariente
authors.affiliation: INSERM, Imagerie cérébrale et handicaps neurologiques UMR 825, Toulouse, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Payoux
authors.affiliation: Aix-Marseille Université, INSERM, INS UMR_S 1106, Marseille, France; Service de Neurologie et Neuropsychologie, APHM Hôpital Timone Adultes, Marseille, France.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Ranjeva
authors.affiliation: Lab Alzheimer's Neuroimaging & Epidemiology, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Rolandi
authors.affiliation: Department of Gerontology, Neurosciences and Orthopedics, Institute of Neurology, Catholic University, Policlinic A. Gemelli Foundation, Rome, Italy.
authors.forename: Paolo Maria
authors.initials: PM
authors.lastname: Rossini
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Leipzig, Leipzig, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Schönknecht
authors.affiliation: SDN Istituto di Ricerca Diagnostica e Nucleare, Napoli, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Soricelli
authors.affiliation: 3rd Neurologic Clinic, Medical School, G. Papanikolaou Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Magda
authors.initials: M
authors.lastname: Tsolaki
authors.affiliation: Department of Neurology, Alzheimer Centre, VU Medical Centre, Amsterdam, the Netherlands.
authors.forename: Pieter Jelle
authors.initials: PJ
authors.lastname: Visser
authors.affiliation: Department of Psychiatry and Psychotherapy, LVR-Hospital Essen, Faculty of Medicine, University of Duisburg-Essen, Essen, Germany; Department of Psychiatry and Psychotherapy, University Medical Center (UMG), Georg-August-University, Goettingen, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Wiltfang
authors.affiliation: Neurosciences Therapeutic Area, GlaxoSmithKline R&D, Stevenage, UK.
authors.forename: Jill C
authors.initials: JC
authors.lastname: Richardson
authors.affiliation: University of Lille, Inserm, CHU Lille, U1171 - Degenerative and Vascular Cognitive Disorders, Lille, France.
authors.forename: Régis
authors.initials: R
authors.lastname: Bordet
authors.affiliation: Mediterranean Institute of Cognitive Neurosciences (INCM), UMR-CNRS (6193), Aix Marseille University, Marseille, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Blin
authors.affiliation: Lab Alzheimer's Neuroimaging & Epidemiology, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy; Memory Clinic and LANVIE - Laboratory of Neuroimaging of Aging, University Hospitals and University of Geneva, Geneva, Switzerland.
authors.forename: Giovanni B
authors.initials: GB
authors.lastname: Frisoni
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D003071:Cognition / Q000502:physiology*; D060825:Cognitive Dysfunction / Q000175:diagnosis* / Q000473:pathology* / Q000523:psychology; D042241:Early Diagnosis; D005260:Female; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D059906:Neuroimaging; D009483:Neuropsychological Tests; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins
keywords: Alzheimer's disease; Amyloid; CANTAB; CSF; Cognitive assessment; Hippocampal volume; Mild cognitive impairment; Prodromal; Tau