title: Cognitive and Brain Profiles Associated with Current Neuroimaging Biomarkers of Preclinical Alzheimer's Disease.
abstract: Neuroimaging biomarkers, namely hippocampal volume loss, temporoparietal hypometabolism, and neocortical β-amyloid (Aβ) deposition, are included in the recent research criteria for preclinical Alzheimer's disease (AD). However, how to use these biomarkers is still being debated, especially regarding their sequence. Our aim was to characterize the cognitive and brain profiles of elders classified as positive or negative for each biomarker to further our understanding of their use in the preclinical diagnosis of AD. Fifty-four cognitively normal individuals (age = 65.8 ± 8.3 years) underwent neuropsychological tests (structural MRI, FDG-PET, and Florbetapir-PET) and were dichotomized into positive or negative independently for each neuroimaging biomarker. Demographic, neuropsychological, and neuroimaging data were compared between positive and negative subgroups. The MRI-positive subgroup had lower executive performances and mixed patterns of lower volume and metabolism in AD-characteristic regions and in the prefrontal cortex. The FDG-positive subgroup showed only hypometabolism, predominantly in AD-sensitive areas extending to the whole neocortex, compared with the FDG-negative subgroup. The amyloid-positive subgroup was older and included more APOE ε4 carriers compared with the amyloid-negative subgroup. When considering MRI and/or FDG biomarkers together (i.e., the neurodegeneration-positive), there was a trend for an inverse relationship with Aβ deposition such that those with neurodegeneration tended to show less Aβ deposition and the reverse was true as well. Our findings suggest that: (1) MRI and FDG biomarkers provide complementary rather than redundant information and (2) relatively young cognitively normal elders tend to have either neurodegeneration or Aβ deposition, but not both, suggesting additive rather than sequential/causative links between AD neuroimaging biomarkers at this age. Significance statement: Neuroimaging biomarkers are included in the recent research criteria for preclinical Alzheimer's disease (AD). However, how to use these biomarkers is still being debated, especially regarding their sequence. Our findings suggest that MRI and FDG-PET biomarkers should be used in combination, offering an additive contribution instead of reflecting the same process of neurodegeneration. Moreover, the present study also challenges the hierarchical use of the neuroimaging biomarkers in preclinical AD because it suggests that the neurodegeneration observed in this population is not due to β-amyloid deposition. Rather, our results suggest that β-amyloid- and tau-related pathological processes may interact but not necessarily appear in a systematic sequence.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité U1077, 14000 Caen, France, Université de Caen Basse-Normandie, Unité Mixte de Recherche (UMR)-S1077, 14000 Caen, France, Centre Hospitalier Universitaire de Caen, U1077, 14000 Caen, France, Department of Nuclear Medicine, Centre Hospitalier Universitaire de Caen, 14000 Caen, France.
authors.forename: Florent L
authors.initials: FL
authors.lastname: Besson
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité U1077, 14000 Caen, France, Université de Caen Basse-Normandie, Unité Mixte de Recherche (UMR)-S1077, 14000 Caen, France, Centre Hospitalier Universitaire de Caen, U1077, 14000 Caen, France, Ecole Pratique des Hautes Etudes, UMR-S1077, 14000 Caen, France.
authors.forename: Renaud
authors.initials: R
authors.lastname: La Joie
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité U1077, 14000 Caen, France, Université de Caen Basse-Normandie, Unité Mixte de Recherche (UMR)-S1077, 14000 Caen, France, Centre Hospitalier Universitaire de Caen, U1077, 14000 Caen, France, Ecole Pratique des Hautes Etudes, UMR-S1077, 14000 Caen, France.
authors.forename: Loïc
authors.initials: L
authors.lastname: Doeuvre
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité U1077, 14000 Caen, France, Université de Caen Basse-Normandie, Unité Mixte de Recherche (UMR)-S1077, 14000 Caen, France, Centre Hospitalier Universitaire de Caen, U1077, 14000 Caen, France, Ecole Pratique des Hautes Etudes, UMR-S1077, 14000 Caen, France.
authors.forename: Malo
authors.initials: M
authors.lastname: Gaubert
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité U1077, 14000 Caen, France, Université de Caen Basse-Normandie, Unité Mixte de Recherche (UMR)-S1077, 14000 Caen, France, Centre Hospitalier Universitaire de Caen, U1077, 14000 Caen, France, Ecole Pratique des Hautes Etudes, UMR-S1077, 14000 Caen, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Mézenge
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité U1077, 14000 Caen, France, Université de Caen Basse-Normandie, Unité Mixte de Recherche (UMR)-S1077, 14000 Caen, France, Centre Hospitalier Universitaire de Caen, U1077, 14000 Caen, France, Ecole Pratique des Hautes Etudes, UMR-S1077, 14000 Caen, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Egret
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité U1077, 14000 Caen, France, Université de Caen Basse-Normandie, Unité Mixte de Recherche (UMR)-S1077, 14000 Caen, France, Centre Hospitalier Universitaire de Caen, U1077, 14000 Caen, France, Ecole Pratique des Hautes Etudes, UMR-S1077, 14000 Caen, France.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Landeau
authors.affiliation: Laboratoire de Développement Méthodologique en Tomographie par Emission de Positons, UMR 6301 "Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales," Commissariat à l'Energie Atomique, Division des Sciences de la Vie/Institut d'Imagerie Biomédicale, Centre National de la Recherche Scientifique, Université de Caen Basse-Normandie, Centre d'Imagerie Cérébrale et de Recherche en Neurosciences, 14000 Caen, France, and.
authors.forename: Louisa
authors.initials: L
authors.lastname: Barré
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité U1077, 14000 Caen, France, Université de Caen Basse-Normandie, Unité Mixte de Recherche (UMR)-S1077, 14000 Caen, France, Centre Hospitalier Universitaire de Caen, U1077, 14000 Caen, France, Ecole Pratique des Hautes Etudes, UMR-S1077, 14000 Caen, France.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Abbas
authors.affiliation: Laboratoire de Développement Méthodologique en Tomographie par Emission de Positons, UMR 6301 "Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales," Commissariat à l'Energie Atomique, Division des Sciences de la Vie/Institut d'Imagerie Biomédicale, Centre National de la Recherche Scientifique, Université de Caen Basse-Normandie, Centre d'Imagerie Cérébrale et de Recherche en Neurosciences, 14000 Caen, France, and.
authors.forename: Meziane
authors.initials: M
authors.lastname: Ibazizene
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité U1077, 14000 Caen, France, Université de Caen Basse-Normandie, Unité Mixte de Recherche (UMR)-S1077, 14000 Caen, France, Centre Hospitalier Universitaire de Caen, U1077, 14000 Caen, France, Ecole Pratique des Hautes Etudes, UMR-S1077, 14000 Caen, France, Department of Neurology, Centre Hospitalier Universitaire de Caen, 14000 Caen, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: de La Sayette
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité U1077, 14000 Caen, France, Université de Caen Basse-Normandie, Unité Mixte de Recherche (UMR)-S1077, 14000 Caen, France, Centre Hospitalier Universitaire de Caen, U1077, 14000 Caen, France, Ecole Pratique des Hautes Etudes, UMR-S1077, 14000 Caen, France.
authors.forename: Béatrice
authors.initials: B
authors.lastname: Desgranges
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité U1077, 14000 Caen, France, Université de Caen Basse-Normandie, Unité Mixte de Recherche (UMR)-S1077, 14000 Caen, France, Centre Hospitalier Universitaire de Caen, U1077, 14000 Caen, France, Ecole Pratique des Hautes Etudes, UMR-S1077, 14000 Caen, France.
authors.forename: Francis
authors.initials: F
authors.lastname: Eustache
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité U1077, 14000 Caen, France, Université de Caen Basse-Normandie, Unité Mixte de Recherche (UMR)-S1077, 14000 Caen, France, Centre Hospitalier Universitaire de Caen, U1077, 14000 Caen, France, Ecole Pratique des Hautes Etudes, UMR-S1077, 14000 Caen, France, chetelat@cyceron.fr.
authors.forename: Gaël
authors.initials: G
authors.lastname: Chételat
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis*; D015415:Biomarkers / Q000032:analysis; D001921:Brain / Q000473:pathology*; D060825:Cognitive Dysfunction / Q000175:diagnosis*; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging / Q000379:methods*; D009410:Nerve Degeneration / Q000175:diagnosis; D059906:Neuroimaging / Q000379:methods; D009483:Neuropsychological Tests; D058225:Plaque, Amyloid / Q000175:diagnosis; D049268:Positron-Emission Tomography
chemical_list: D015415:Biomarkers
keywords: Alzheimer's disease; FDG; MRI; PET; amyloid; biomarkers