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1. Cognitive changes of older adults with an equivocal amyloid load

Author

Bruno Vellas, Laure Saint-Aubert, Mapt, Julien Delrieu, Pierre Payoux, Kristell Pothier, Philipe de Souto Barreto, Claudie Hooper, Psychologie des âges de la vie et adaptation (PAVeA), Université de Tours (UT), Toulouse Neuro Imaging Center (ToNIC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Toulouse [Toulouse], and Université de Tours

Subjects
Male, medicine.medical_specialty, Aging, Amyloid, Neurology, Population, Disease, Neuropsychological Tests, 03 medical and health sciences, Executive Function, 0302 clinical medicine, Cognition, Neuroimaging, Memory, medicine, Humans, Cognitive Dysfunction, 030212 general & internal medicine, Cognitive decline, education, ComputingMilieux_MISCELLANEOUS, Neuroradiology, Aged, education.field_of_study, Aniline Compounds, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, Brain, Executive functions, Positron-Emission Tomography, [SCCO.PSYC]Cognitive science/Psychology, Observational study, Ethylene Glycols, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), Radiopharmaceuticals, business, 030217 neurology & neurosurgery, Clinical psychology, Follow-Up Studies
Abstract

Observational and interventional studies addressing the link between amyloid (Aβ) burden and cognitive decline are increasing, but a clear definition of amyloid positivity is still lacking. This may represent a great stake for therapeutic studies enrolling Aβ + patients only. The main objective of this study was to define a population with “equivocal” amyloid status, and evaluate their cognitive changes. Sixty-five participants over 75 years old, from the Control group of the interventional MAPT study, at risk to develop Alzheimer’s disease, were included. Participants were classified into three groups in terms of amyloid load: Aβ +, Aβ − and Equivocal participants (according to visual reading, global standardized uptake (SUVR) cut-offs, or a k-mean clustering method). The cognitive changes over time (memory, executive functions, attention and processing speed) of this Equivocal group were then compared to Aβ + and Aβ − participants. When classified by visual read, Equivocal participants’ memory scores were comparable to the Aβ- participants, and greater than in Aβ + participants over time. Secondary analyses, using SUVR cut-offs classification, showed different trajectories with Equivocal participants being comparable to the Aβ + participants, and lower than Aβ-, on executive performance over time. This original work pointed out a population that may be of great interest for interventional studies, raising the question of how amyloid status should be defined and integrated in such studies. These findings should be replicated in future studies on larger datasets, to confirm what methodological approach would be the most suitable to highlight this specific neuroimaging entity.

Published
2019
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2. Case report of Lewy body disease mimicking Creutzfeldt-Jakob disease in a 44-year-old man

Author

Katell Peoc'h, Eric Guedj, A. Vital, Fabienne Ory Magne, Michèle Puel, Suzanne Lesage, Pierre Payoux, Laure Saint-Aubert, Hervé Dumas, Christine Brefel Courbon, Jérémie Pariente, Jean-Philippe Brandel, Karolinska Institutet [Stockholm], Neurologie vasculaire, pathologie neuro-dégénérative et explorations fonctionnelles du système nerveux [Toulouse], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Imagerie cérébrale et handicaps neurologiques (ICHN), Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de neuroradiologie [CHU Toulouse], Service de Médecine Nucléaire [Toulouse], Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de pathologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), AP-HP Service de Biochimie, Fondation FondaMental, U942 Hôpital Lariboisière, Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Pharmacologie Clinique, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pôle Cardiovasculaire et Métabolique [CHU Toulouse], Service de Médecine Nucléaire - Pierre-Paul Riquet [CHU Toulouse], Pôle imagerie médicale [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service Pharmacologie Clinique [CHU Toulouse], Pôle Santé publique et médecine publique [CHU Toulouse], Imagerie cérébrale et handicaps neurologiques, Université Paul Sabatier - Toulouse 3 (UPS) - Institut National de la Santé et de la Recherche Médicale (INSERM), Service de neurologie [CHU Toulouse], Service de médecine nucléaire [CHU Toulouse], Cellule nationale de référence des maladies de Creutzfeldt-Jakob, Institut du Cerveau et de la Moëlle Epinière (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC) - Institut National de la Santé et de la Recherche Médicale (INSERM) - CHU Pitié-Salpêtrière [APHP] - Centre National de la Recherche Scientifique (CNRS), Université Bordeaux Segalen - Bordeaux 2 - CHU Bordeaux [Bordeaux] - Groupe hospitalier Pellegrin, Institut de Neurosciences de la Timone [Marseille] (INT), and Aix Marseille Université (AMU) - Assistance Publique - Hôpitaux de Marseille (APHM) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS)

Subjects
Adult, Lewy Body Disease, Male, medicine.medical_specialty, Pediatrics, Pathology, Neurology, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Diagnostico diferencial, Dementia with Lewy bodies, Clinical Neurology, Case Report, Neuroimaging, Disease, Creutzfeldt-Jakob Syndrome, Delusions, 14–3–3 protein, Imaging, Diagnosis, Differential, 03 medical and health sciences, Fatal Outcome, 0302 clinical medicine, Parkinsonian Disorders, Fluorodeoxyglucose F18, Diagnosis, medicine, Genetics, Humans, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], business.industry, Brain, General Medicine, medicine.disease, Magnetic Resonance Imaging, 030227 psychiatry, 3. Good health, 14-3-3 Proteins, Young population, Positron-Emission Tomography, Neurology (clinical), Neurosurgery, Cognition Disorders, business, Lewy body disease, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Follow-Up Studies
Abstract

Background Few patients are reported with dementia with Lewy bodies before fifty years-old, which may partly reflect the difficulty of accurate diagnosis in young population. We report the case of a 44-year-old male with pathologically confirmed sporadic dementia with Lewy bodies, who did not fulfil the revised clinical criteria for this disease. Case presentation We document this atypical case with clinical and cognitive evaluation, imaging, biochemistry, genetics and pathology investigations. Creutzfeldt-Jakob disease was first suspected in this patient with no previous medical history, who developed acute and rapid cognitive impairment, L-dopa-non-responsive parkinsonism, and delusion. Positive 14–3–3 protein was initially detected in cerebrospinal fluid and until the late stages of the disease. Severe atrophy with no diffusion hypersignal was found on structural MRI as well as an extensive hypometabolism on 18F-FDG-PET, in comparison to age-matched healthy volunteers. Genetic investigation found no alpha-synuclein gene mutation. The patient died within 5 years, and post-mortem examination found numerous Lewy bodies and Lewy neurites consistent with pure Lewy body disease. Conclusions This comprehensively described case illustrates that dementia with Lewy bodies can occur in young patients with atypical clinical presentation. Biochemistry and neuroimaging investigations can sometimes be insufficient to allow accurate diagnostic. More specific markers to support such diagnosis are needed. Electronic supplementary material The online version of this article (doi:10.1186/s12883-016-0643-y) contains supplementary material, which is available to authorized users.

Published
2016
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