The impact of automated hippocampal volumetry on diagnostic confidence in patients with suspected Alzheimer's disease: A European Alzheimer's Disease Consortium study

Paolo Bosco; Alberto Redolfi; Martina Bocchetta; Clarissa Ferrari; Anna Mega; Samantha Galluzzi; Mark Austin; Andrea Chincarini; D Louis Collins; Simon Duchesne; Bénédicte Maréchal; Alexis Roche; Francesco Sensi; Robin Wolz; Montserrat Alegret; Frederic Assal; Mircea Balasa; Christine Bastin; Anastasia Bougea; Derya Durusu Emek-Savaş; Sebastiaan Engelborghs; Timo Grimmer; Galina Grosu; Milica G Kramberger; Brian Lawlor; Gorana Mandic Stojmenovic; Mihaela Marinescu; Patrizia Mecocci; José Luis Molinuevo; Ricardo Morais; Ellis Niemantsverdriet; Flavio Nobili; Konstantinos Ntovas; Sarah O'Dwyer; George P Paraskevas; Luca Pelini; Agnese Picco; Eric Salmon; Isabel Santana; Oscar Sotolongo-Grau; Luiza Spiru; Elka Stefanova; Katarina Surlan Popovic; Magda Tsolaki; Görsev G Yener; Dina Zekry; Giovanni B Frisoni

doi:10.1016/j.jalz.2017.01.019

The impact of automated hippocampal volumetry on diagnostic confidence in patients with suspected Alzheimer's disease: A European Alzheimer's Disease Consortium study

Alzheimers Dement. 2017 Sep;13(9):1013-1023. doi: 10.1016/j.jalz.2017.01.019. Epub 2017 Mar 3.

Authors

Paolo Bosco¹, Alberto Redolfi¹, Martina Bocchetta², Clarissa Ferrari³, Anna Mega¹, Samantha Galluzzi¹, Mark Austin⁴, Andrea Chincarini⁵, D Louis Collins⁶, Simon Duchesne⁷, Bénédicte Maréchal⁸, Alexis Roche⁸, Francesco Sensi⁵, Robin Wolz⁴, Montserrat Alegret⁹, Frederic Assal¹⁰, Mircea Balasa¹¹, Christine Bastin¹², Anastasia Bougea¹³, Derya Durusu Emek-Savaş¹⁴, Sebastiaan Engelborghs¹⁵, Timo Grimmer¹⁶, Galina Grosu¹⁷, Milica G Kramberger¹⁸, Brian Lawlor¹⁹, Gorana Mandic Stojmenovic²⁰, Mihaela Marinescu²¹, Patrizia Mecocci²², José Luis Molinuevo¹¹, Ricardo Morais²³, Ellis Niemantsverdriet²⁴, Flavio Nobili²⁵, Konstantinos Ntovas²⁶, Sarah O'Dwyer¹⁹, George P Paraskevas¹³, Luca Pelini²², Agnese Picco²⁷, Eric Salmon¹², Isabel Santana²⁸, Oscar Sotolongo-Grau⁹, Luiza Spiru²⁹, Elka Stefanova³⁰, Katarina Surlan Popovic³¹, Magda Tsolaki²⁶, Görsev G Yener³², Dina Zekry³³, Giovanni B Frisoni³⁴

Affiliations

¹ Laboratory of Alzheimer's Neuroimaging and Epidemiology, IRCCS Istituto Centro S. Giovanni di Dio Fatebenefratelli, Brescia, Italy.
² Department of Neurodegenerative Disease, Dementia Research Centre, UCL Institute of Neurology, London, UK.
³ IRCCS Istituto Centro S. Giovanni di Dio Fatebenefratelli, Brescia, Italy.
⁴ IXICO Plc, London, UK.
⁵ INFN, Genova, Italy.
⁶ McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada; True Positive Medical Devices Inc., Quebec City, Quebec, Canada.
⁷ True Positive Medical Devices Inc., Quebec City, Quebec, Canada.
⁸ Advanced Clinical Imaging Technology (HC CMEA SUI DI BM PI), Siemens Healthcare AG, Lausanne, Switzerland; Department of Radiology, University Hospital (CHUV), Lausanne, Switzerland; LTS5, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
⁹ Alzheimer Research Center and Memory Clinic, Fundació ACE, Institut Català de Neurociències Aplicades, Barcelona, Spain.
¹⁰ University Hospitals and University of Geneva, Geneva, Switzerland.
¹¹ Alzheimer's and Other Cognitive Disorder Unit, Hospital Clinic, Barcelona, Spain.
¹² GIGA-CRC In vivo Imaging and Memory Clinic, University of Liège, Liège, Belgium.
¹³ First Department of Neurology, Eginition Hospital Kapodistrian University, Medical School of Athens, Athens, Greece.
¹⁴ Department of Psychology, Dokuz Eylül University, Izmir, Turkey; Izmir International Biomedicine and Genome Center, Dokuz Eylul University, Izmir, Turkey.
¹⁵ Reference Center for Biological Markers of Dementia (BIODEM), University of Antwerp, Antwerp, Belgium; Memory Clinic and Department of Neurology, Hospital Network Antwerp (ZNA) Hoge Beuken and Middelheim, Antwerp, Belgium.
¹⁶ Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
¹⁷ Radiology and Medical Imagery, Elias University Clinical Hospital, Bucharest, Romania.
¹⁸ Department of Neurology, Centre for Cognitive Impairments, University Medical Center Ljubljana, Ljubljana, Slovenia.
¹⁹ Mercer's Institute for Successful Ageing, St. James's Hospital, Dublin, Ireland.
²⁰ Institute of Neurology, CCS, Belgrade, Serbia.
²¹ Department of Geriatrics-Gerontology and Old Age Psychiatry, Elias University Clinic, Bucharest, Romania.
²² Istituto di Gerontologia e Geriatria, Università degli Studi di Perugia, Perugia, Italy.
²³ Medical Imaging Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.
²⁴ Reference Center for Biological Markers of Dementia (BIODEM), University of Antwerp, Antwerp, Belgium.
²⁵ Clinical Neurology (DINOGMI), University of Genoa and IRCCS AOU San Martino-IST, Genoa, Italy.
²⁶ 3rd Department of Neurology, Aristotle University of Thessaloniki, Thessaloniki, Greece.
²⁷ Clinical Neurology (DINOGMI), University of Genoa and IRCCS AOU San Martino-IST, Genoa, Italy; Memory Clinic and LANVIE-Laboratory of Neuroimaging of Aging, University Hospitals and University of Geneva, Geneva, Switzerland.
²⁸ Neurology Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.
²⁹ Carol Davila University of Medicine, Bucharest, Romania; Ana Aslan Intl Foundation-Memory Clinic, Bucharest, Romania.
³⁰ Institute of Neurology, CCS, Belgrade, Serbia; Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
³¹ Clinical Institute of Radiology, University Medical Center Ljubljana, Slovenia.
³² Izmir International Biomedicine and Genome Center, Dokuz Eylul University, Izmir, Turkey; Department of Neurology, Dokuz Eylül University, Izmir, Turkey; Brain Dynamics Multidisciplinary Research Center, Dokuz Eylül University, Izmir, Turkey.
³³ Department of Internal Medicine, Rehabilitation and Geriatrics, University Hospitals and University of Geneva, Geneva, Switzerland.
³⁴ Laboratory of Alzheimer's Neuroimaging and Epidemiology, IRCCS Istituto Centro S. Giovanni di Dio Fatebenefratelli, Brescia, Italy; Memory Clinic and LANVIE-Laboratory of Neuroimaging of Aging, University Hospitals and University of Geneva, Geneva, Switzerland. Electronic address: gfrisoni@fatebenefratelli.eu.

PMID: 28263741
DOI: 10.1016/j.jalz.2017.01.019

Abstract

Introduction: Hippocampal volume is a core biomarker of Alzheimer's disease (AD). However, its contribution over the standard diagnostic workup is unclear.

Methods: Three hundred fifty-six patients, under clinical evaluation for cognitive impairment, with suspected AD and Mini-Mental State Examination ≥20, were recruited across 17 European memory clinics. After the traditional diagnostic workup, diagnostic confidence of AD pathology (DCAD) was estimated by the physicians in charge. The latter were provided with the results of automated hippocampal volumetry in standardized format and DCAD was reassessed.

Results: An increment of one interquartile range in hippocampal volume was associated with a mean change of DCAD of -8.0% (95% credible interval: [-11.5, -5.0]). Automated hippocampal volumetry showed a statistically significant impact on DCAD beyond the contributions of neuropsychology, ¹⁸F-fluorodeoxyglucose positron emission tomography/single-photon emission computed tomography, and cerebrospinal fluid markers (-8.5, CrI: [-11.5, -5.6]; -14.1, CrI: [-19.3, -8.8]; -10.6, CrI: [-14.6, -6.1], respectively).

Discussion: There is a measurable effect of hippocampal volume on DCAD even when used on top of the traditional diagnostic workup.

Keywords: Alzheimer's disease; Biomarkers; Diagnostic confidence of AD; Hippocampal volume; Medial temporal lobe atrophy.

Publication types

Multicenter Study

MeSH terms

Alzheimer Disease / cerebrospinal fluid
Alzheimer Disease / complications
Alzheimer Disease / diagnosis*
Alzheimer Disease / pathology*
Amyloid beta-Peptides / cerebrospinal fluid
Cognition Disorders / diagnostic imaging
Cognition Disorders / etiology*
Diagnosis, Computer-Assisted*
Diagnosis, Differential
Disease Progression
Europe
Female
Fluorodeoxyglucose F18 / metabolism
Hippocampus / pathology*
Humans
Male
Neuropsychological Tests
Peptide Fragments / cerebrospinal fluid
Positron-Emission Tomography
Tomography, Emission-Computed, Single-Photon
tau Proteins / cerebrospinal fluid

Substances

Amyloid beta-Peptides
Peptide Fragments
amyloid beta-protein (1-42)
tau Proteins
Fluorodeoxyglucose F18