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1. Applicability of in vivo staging of regional amyloid burden in a cognitively normal cohort with subjective memory complaints: the INSIGHT-preAD study.

Author

Sakr FA, Grothe MJ, Cavedo E, Jelistratova I, Habert MO, Dyrba M, Gonzalez-Escamilla G, Bertin H, Locatelli M, Lehericy S, Teipel S, Dubois B, and Hampel H

Subjects
Aged, Aged, 80 and over, Alzheimer Disease metabolism, Alzheimer Disease psychology, Cognitive Dysfunction metabolism, Cognitive Dysfunction psychology, Cohort Studies, Female, Follow-Up Studies, Humans, Male, Mental Status and Dementia Tests, Alzheimer Disease diagnostic imaging, Amyloid metabolism, Cognition physiology, Cognitive Dysfunction diagnostic imaging, Diagnostic Self Evaluation, Memory physiology
Abstract

Background: Current methods of amyloid PET interpretation based on the binary classification of global amyloid signal fail to identify early phases of amyloid deposition. A recent analysis of 18F-florbetapir PET data from the Alzheimer's disease Neuroimaging Initiative cohort suggested a hierarchical four-stage model of regional amyloid deposition that resembles neuropathologic estimates and can be used to stage an individual's amyloid burden in vivo. Here, we evaluated the validity of this in vivo amyloid staging model in an independent cohort of older people with subjective memory complaints (SMC). We further examined its potential association with subtle cognitive impairments in this population at elevated risk for Alzheimer's disease (AD)., Methods: The monocentric INSIGHT-preAD cohort includes 318 cognitively intact older individuals with SMC. All individuals underwent 18F-florbetapir PET scanning and extensive neuropsychological testing. We projected the regional amyloid uptake signal into the previously proposed hierarchical staging model of in vivo amyloid progression. We determined the adherence to this model across all cases and tested the association between increasing in vivo amyloid stage and cognitive performance using ANCOVA models., Results: In total, 156 participants (49%) showed evidence of regional amyloid deposition, and all but 2 of these (99%) adhered to the hierarchical regional pattern implied by the in vivo amyloid progression model. According to a conventional binary classification based on global signal (SUVR Cereb  = 1.10), individuals in stages III and IV were classified as amyloid-positive (except one in stage III), but 99% of individuals in stage I and even 28% of individuals in stage II were classified as amyloid-negative. Neither in vivo amyloid stage nor conventional binary amyloid status was significantly associated with cognitive performance in this preclinical cohort., Conclusions: The proposed hierarchical staging scheme of PET-evidenced amyloid deposition generalizes well to data from an independent cohort of older people at elevated risk for AD. Future studies will determine the prognostic value of the staging approach for predicting longitudinal cognitive decline in older individuals at increased risk for AD.

Published
2019
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2. Evaluation of amyloid status in a cohort of elderly individuals with memory complaints: validation of the method of quantification and determination of positivity thresholds.

Author

Habert MO, Bertin H, Labit M, Diallo M, Marie S, Martineau K, Kas A, Causse-Lemercier V, Bakardjian H, Epelbaum S, Chételat G, Houot M, Hampel H, Dubois B, and Mangin JF

Subjects
Aged, Aniline Compounds, Cognition, Ethylene Glycols, Female, Humans, Image Processing, Computer-Assisted, Male, Reference Values, Software, Amyloid metabolism, Memory, Positron-Emission Tomography methods, Positron-Emission Tomography standards
Abstract

Objective: Our aim is to validate the process steps implemented by the French CATI platform to assess amyloid status, obtained from 18F-Florbetapir PET scans, in a cohort of 318 cognitively normal subjects participating in the INSIGHT-preAD study. Our objective was to develop a method with partial volume effect correction (PVEC) on untransformed PET images, using an automated pipeline ("RACHEL") adapted to large series of patients and including quality checks of results., Methods: We compared RACHEL using different options (with and without PVEC, different sets of regions of interest), to two other methods validated in the literature, referred as the "AVID" and "CAEN" methods. A standard uptake value ratio (SUVR) was obtained with the different methods for participants to another French study, IMAP, including 26 normal elderly controls (NEC), 11 patients with mild cognitive impairment (MCI) and 16 patients with Alzheimer's disease (AD). We determined two cutoffs for RACHEL method by linear correlation with the other methods and applied them to the INSIGHT-preAD subjects., Results: RACHEL including PVEC and a combination of the whole cerebellum and the pons as a reference region allowed the best discrimination between NEC and AD participants. A strong linear correlation was found between RACHEL and the other two methods and yielded the two cutoffs of 0.79 and 0.88. According to the more conservative threshold, 19.8% of the INSIGHT-preAD subjects would be considered amyloid positive, and 27.7% according to the more liberal threshold., Conclusions: With our method, we clearly discriminated between NEC with negative amyloid status and patients with clinical AD. Using a linear correlation with other validated cutoffs, we could infer our own positivity thresholds and apply them to an independent population. This method might be useful to the community, especially when the optimal cutoff could not be obtained from a population of healthy young adults or from correlation with post-mortem results.

Published
2018
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3. MiRNA-15b and miRNA-125b are associated with regional Aβ-PET and FDG-PET uptake in cognitively normal individuals with subjective memory complaints

Author

Vergallo, Andrea, Lista, Simone, group, INSIGHT-preAD study, Lucía, Alejandro, Mango, Dalila, Mapstone, Mark, Neri, Christian, Nisticò, Robert, O'Bryant, Sid E, Palermo, Giovanni, Perry, George, Ritchie, Craig, Rossi, Simone, Initiative, Alzheimer Precision Medicine, Saidi, Amira, Santarnecchi, Emiliano, Schneider, Lon S, Sporns, Olaf, Toschi, Nicola, Valenzuela, Pedro L, Vellas, Bruno, Verdooner, Steven R, Villain, Nicolas, Giudici, Kelly Virecoulon, Bakardjian, Hovagim, Watling, Mark, Welikovitch, Lindsay A, Woodcock, Janet, Younesi, Erfan, Zugaza, José L, Benali, Habib, Bertin, Hugo, Bonheur, Joel, Boukadida, Laurie, Boukerrou, Nadia, Cavedo, Enrica, Chiesa, Patrizia, Zhao, Yuhai, Colliot, Olivier, Dubois, Bruno, Dubois, Marion, Epelbaum, Stéphane, Gagliardi, Geoffroy, Genthon, Remy, Habert, Marie-Odile, Hampel, Harald, Houot, Marion, Kas, Aurélie, Lemercier, Pablo, Lamari, Foudil, Levy, Marcel, Metzinger, Christiane, Mochel, Fanny, Nyasse, Francis, Poisson, Catherine, Potier, Marie-Claude, Revillon, Marie, Santos, Antonio, Teipel, Stefan J, Andrade, Katia Santos, Sole, Marine, Surtee, Mohmed, de Schotten, Michel Thiebaut, Younsi, Nadjia, Afshar, Mohammad, Aguilar, Lisi Flores, Akman-Anderson, Leyla, Arenas, Joaquín, Ávila, Jesús, Babiloni, Claudio, Baldacci, Filippo, Batrla, Richard, Benda, Norbert, Black, Keith L, Bokde, Arun L W, Bonuccelli, Ubaldo, Broich, Karl, Cacciola, Francesco, Caraci, Filippo, Caruso, Giuseppe, Castrillo, Juan, Ceravolo, Roberto, Chiesa, Patrizia A, Corbo, Massimo, Corvol, Jean-Christophe, Cuello, Augusto Claudio, Cummings, Jeffrey L, Depypere, Herman, Duggento, Andrea, Emanuele, Enzo, Escott-Price, Valentina, Federoff, Howard, Ferretti, Maria Teresa, Fiandaca, Massimo, Frank, Richard A, Garaci, Francesco, Lukiw, Walter J, Geerts, Hugo, Giacobini, Ezio, Giorgi, Filippo S, Goetzl, Edward J, Graziani, Manuela, Haberkamp, Marion, Hänisch, Britta, Herholz, Karl, Hernandez, Felix, Imbimbo, Bruno P, Kapogiannis, Dimitrios, Karran, Eric, Kiddle, Steven J, Kim, Seung H, Koronyo, Yosef, Koronyo-Hamaoui, Maya, Langevin, Todd, Lehéricy, Stéphane, Llavero, Francisco, Lorenceau, Jean, Ministre de l'Enseignement Supérieur, de la Recherche et de l'Innovation (France), Sorbonne Université, AXA Research Fund, Fondation partenariale, Fondation pour la Recherche sur Alzheimer, Investissement d’Avenir French program, Vergallo, Andrea [0000-0002-0208-6384], Apollo - University of Cambridge Repository, Alzheimer Precision Medicine [CHU Pitié-Salpétriêre] (GRC 21 AMP), 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), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-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)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de la Mémoire et de la Maladie d'Alzheimer [Paris] (IM2A), Sorbonne Université (SU), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Louisiana State University (LSU), University of Rostock, Laboratoire d'Imagerie Biomédicale (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CATI Multicenter Neuroimaging Platform (CATI), Service de médecine nucléaire [CHU Pitié-Salpétrière], Observatoire Midi-Pyrénées (OMP), Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD), Department of Psychiatry, Psychosomatic Medicine and Psychotherapy [Goethe Universität], Goethe-Universität Frankfurt am Main, HAL-SU, Gestionnaire, Alzheimer Precision Medicine [CHU Pitié-Salpétriêre] (GRC 21 APM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de la Mémoire et de la Maladie d'Alzheimer [CHU Pitié-Salpétriêre] (IM2A), Service de Médecine nucléaire [CHU Pitié-Salpétrière], Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France, Groupe de recherche clinique Alzheimer Precision Medicine (GRC 21 - APM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire d'Imagerie Biomédicale [Paris] (LIB), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de neurologie 1 [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)

Subjects
Apolipoprotein E, Aging, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Disease, miRNAs plasma concentrations, Alzheimer's Disease, amyloid-β (Aβ)-positron emission tomography (Aβ-PET), Prognostic markers, 0302 clinical medicine, Medicine, Psychology, Aetiology, education.field_of_study, MicroARNs, Settore FIS/07, amyloid, Brain, Pathophysiology, ALZHEIMERS-DISEASE, Psychiatry and Mental health, Alzheimer's disease (AD), Public Health and Health Services, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], MiRNA, medicine.medical_specialty, 18F-fluorodeoxyglucose-PET (18F-FDG-PET), BIOMARKERS, Neurociencias, Clinical Sciences, Molecular neuroscience, Predictive markers, Article, VESICLES, lcsh:RC321-571, 03 medical and health sciences, Memory, Clinical Research, Alzheimer Disease, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], microRNA, Genetics, Humans, education, Biological Psychiatry, Prevention, Memory, MiRNA, Alzheimer, biological markers, amyloid, 030104 developmental biology, Endocrinology, Cross-Sectional Studies, Positron-Emission Tomography, CELLS, Dementia, diagnostic imaging [Alzheimer Disease], INSIGHT-preAD study group, 030217 neurology & neurosurgery, [SDV.NEU.SC] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, 0301 basic medicine, genetics [Alzheimer Disease], Pilot Projects, Neurodegenerative, Medicine and Health Sciences, 2.1 Biological and endogenous factors, genetics [MicroRNAs], MIR-125B, screening and diagnosis, PLASMA, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Detection, Real-time polymerase chain reaction, Neurological, medicine.symptom, biological markers, Biotechnology, EXPRESSION, Population, metabolism [Amyloid beta-Peptides], Asymptomatic, Salud mental, Cellular and Molecular Neuroscience, ADULT, Fluorodeoxyglucose F18, Internal medicine, Acquired Cognitive Impairment, ddc:610, Allele, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, diagnostic imaging [Brain], Psiquiatría, Amyloid beta-Peptides, Enfermedad de alzheimer, business.industry, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Neurosciences, Alzheimer Precision Medicine Initiative, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Brain Disorders, 4.1 Discovery and preclinical testing of markers and technologies, MicroRNAs, metabolism [Brain], Alzheimer, business, Psychiatric disorders
Abstract

There is substantial experimental evidence for dysregulation of several microRNA (miRNA) expression levels in Alzheimer’s disease (AD). MiRNAs modulate critical brain intracellular signaling pathways and are associated with AD core pathophysiological mechanisms. First, we conducted a real-time quantitative PCR-based pilot study to identify a set of brain-enriched miRNAs in a monocentric cohort of cognitively normal individuals with subjective memory complaints, a condition associated with increased risk of AD. Second, we investigated the impact of age, sex, and the Apolipoprotein E ε4 (APOE ε4) allele, on the identified miRNA plasma concentrations. In addition, we explored the cross-sectional and longitudinal association of the miRNAs plasma concentrations with regional brain metabolic uptake using amyloid-β (Aβ)-positron emission tomography (Aβ-PET) and F-fluorodeoxyglucose-PET (F-FDG-PET). We identified a set of six brain-enriched miRNAs—miRNA-125b, miRNA-146a, miRNA-15b, miRNA-148a, miRNA-26b, and miRNA-100. Age, sex, and APOE ε4 allele were not associated with individual miRNA abundance. MiRNA-15b concentrations were significantly lower in the Aβ-PET-positive compared to Aβ-PET-negative individuals. Furthermore, we found a positive effect of the miRNA-15b*time interaction on regional metabolic F-FDG-PET uptake in the left hippocampus. Plasma miRNA-125b concentrations, as well as the miRNA-125b*time interaction (over a 2-year follow-up), were negatively associated with regional Aβ-PET standard uptake value ratio in the right anterior cingulate cortex. At baseline, we found a significantly negative association between plasma miRNA-125b concentrations and F-FDG-PET uptake in specific brain regions. In an asymptomatic at-risk population for AD, we show significant associations between plasma concentrations of miRNA-125b and miRNA-15b with core neuroimaging biomarkers of AD pathophysiology. Our results, coupled with existing experimental evidence, suggest a potential protective anti-Aβ effect of miRNA-15b and a biological link between miRNA-125b and Aβ-independent neurotoxic pathways., “Investissement d’Avenir” (ANR-10-AIHU-06) French program. The study was promoted in collaboration with the “CHU de Bordeaux” (coordination CIC EC7), the promoter of Memento cohort, funded by the Foundation Plan-Alzheimer. The study was further supported by AVID/Lilly. CATI is a French neuroimaging platform funded by the French Plan Alzheimer (available at http://cati-neuroimaging.com). A.V. is an employee of Eisai Inc. This work has been performed during his previous position at Sorbonne University, Paris, France. H.H. is an employee of Eisai Inc. This work has been performed during his previous position at Sorbonne University, Paris, France. At Sorbonne University he was supported by the AXA Research Fund, the “Fondation partenariale Sorbonne Université” and the “Fondation pour la Recherche sur Alzheimer

Published
2021
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4. Sex differences in functional and molecular neuroimaging biomarkers of Alzheimer's disease in cognitively normal older adults with subjective memory complaints

Author

Cavedo, Enrica, Chiesa, Patrizia A., Houot, Marion, Ferretti, Maria Teresa, Grothe, Michel J., Teipel, Stefan J., Lista, Simone, Habert, Marie-Odile, Potier, Marie-Claude, Dubois, Bruno, Hampel, Harald, Bakardjian, Hovagim, Benali, Habib, Bertin, Hugo, Bonheur, Joel, Boukadida, Laurie, Boukerrou, Nadia, Chiesa, Patrizia, Colliot, Olivier, Dubois, Marion, Epelbaum, Stéphane, Gagliardi, Geoffroy, Genthon, Remy, Kas, Aurélie, Lamari, Foudil, Levy, Marcel, Metzinger, Christiane, Mochel, Fanny, Nyasse, Francis, Poisson, Catherine, Revillon, Marie, Santos, Antonio, Andrade, Katia Santos, Sole, Marine, Surtee, Mohmed, de Schotten, Michel Thiebaud, Vergallo, Andrea, Younsi, Nadjia, Aguilar, Lisi Flores, Babiloni, Claudio, Baldacci, Filippo, Benda, Norbert, Black, Keith L., Bokde, Arun L. W., Bonuccelli, Ubaldo, Broich, Karl, Bun, René S., Cacciola, Francesco, Castrillo, Juan, Ceravolo, Roberto, Coman, Cristina-Maria, Corvol, Jean-Christophe, Cuello, Augusto Claudio, Cummings, Jeffrey L., Depypere, Herman, Duggento, Andrea, Durrleman, Stanley, Escott-Price, Valentina, Federoff, Howard, Fiandaca, Massimo, Frank, Richard A., Garaci, Francesco, George, Nathalie, Giorgi, Filippo S., Graziani, Manuela, Haberkamp, Marion, Herholz, Karl, Karran, Eric, Kim, Seung H., Koronyo, Yosef, Koronyo-Hamaoui, Maya, Langevin, Todd, Lehéricy, Stéphane, Lorenceau, Jean, Mapstone, Mark, Neri, Christian, Nisticò, Robert, Nyasse-Messene, Francis, O'Bryant, Sid E., Perry, George, Ritchie, Craig, Rojkova, Katrine, Rossi, Simone, Saidi, Amira, Santarnecchi, Emiliano, Schneider, Lon S., Sporns, Olaf, Toschi, Nicola, Verdooner, Steven R., Villain, Nicolas, Welikovitch, Lindsay A., Woodcock, Janet, and Younesi, Erfan

Subjects
Male, 0301 basic medicine, Apolipoprotein E, Oncology, Aging, aging, Alzheimer's disease, amyloid, APOE, basal forebrain, cognitively intact older individuals, cortical thickness, FDG-PET, hippocampus, metabolism, sex, epidemiology, health policy, developmental neuroscience, neurology (clinical), geriatrics and gerontology, cellular and molecular neuroscience, psychiatry and mental health, Epidemiology, Cognitively intact older individuals, Precuneus, Hippocampus, genetics [Alzheimer Disease], physiopathology [Brain], Cohort Studies, 0302 clinical medicine, genetics [Memory Disorders], Risk Factors, Neural Pathways, Medicine, Aged, 80 and over, Sex Characteristics, Health Policy, Settore FIS/07, Neurodegeneration, Brain, Human brain, Magnetic Resonance Imaging, diagnostic imaging [Neural Pathways], Psychiatry and Mental health, metabolism [Glucose], medicine.anatomical_structure, Female, Sex, Amyloid, medicine.medical_specialty, Rest, diagnostic imaging [Memory Disorders], physiopathology [Alzheimer Disease], Cortical thickness, Basal forebrain, Diagnostic Self Evaluation, 03 medical and health sciences, Cellular and Molecular Neuroscience, Apolipoproteins E, Sex Factors, Developmental Neuroscience, Alzheimer Disease, Internal medicine, physiopathology [Memory Disorders], Humans, ddc:610, diagnostic imaging [Brain], Metabolism, Anterior cingulate cortex, metabolism [Amyloid], Aged, Memory Disorders, Resting state fMRI, business.industry, physiopathology [Neural Pathways], medicine.disease, Glucose, 030104 developmental biology, psychology [Memory Disorders], Positron-Emission Tomography, Posterior cingulate, genetics [Apolipoproteins E], Neurology (clinical), Geriatrics and Gerontology, business, diagnostic imaging [Alzheimer Disease], 030217 neurology & neurosurgery
Abstract

Observational multimodal neuroimaging studies indicate sex differences in Alzheimer's disease pathophysiological markers.Positron emission tomography brain amyloid load, neurodegeneration (hippocampus and basal forebrain volumes adjusted to total intracranial volume, cortical thickness, and 2-deoxy-2-[fluorine-18]fluoro-D-glucose-positron emission tomography metabolism), and brain resting-state functional connectivity were analyzed in 318 cognitively intact older adults from the INSIGHT-preAD cohort (female n = 201, male n = 117). A linear mixed-effects model was performed to investigate sex effects and sex∗apolipoprotein E genotype interaction on each marker as well as sex∗amyloid group interaction for non-amyloid markers.Men compared with women showed higher anterior cingulate cortex amyloid load (P = .009), glucose hypometabolism in the precuneus (P = .027), posterior cingulate (P .001) and inferior parietal (P = .043) cortices, and lower resting-state functional connectivity in the default mode network (P = .024). No brain volumetric markers showed differences between men and women. Sex∗apolipoprotein E genotype and sex∗amyloid status interactions were not significant.Our findings suggest that cognitively intact older men compared with women have higher resilience to pathophysiological processes of Alzheimer's disease.

Published
2018
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5. Multimorbidity Is Associated with Preclinical Alzheimer’s Disease Neuroimaging Biomarkers.

Author

Mendes, Aline, Levy, Marcel, Dubois, Bruno, Epelbaum, Stéphane, Tezenas du Montcel, Sophie, Bertrand, Anne, Habert, Marie-Odile, and Bertin, Hugo

Subjects
ALZHEIMER'S disease diagnosis, ALZHEIMER'S disease risk factors, HIPPOCAMPUS physiology, AFFECTIVE disorders, AUTOMATION, BIOMARKERS, COGNITION, DEOXY sugars, ALCOHOL drinking, LONGITUDINAL method, NEUROPSYCHOLOGICAL tests, NEURORADIOLOGY, OBESITY, RADIOPHARMACEUTICALS, REGRESSION analysis, SLEEP apnea syndromes, POSITRON emission tomography, COMORBIDITY, CROSS-sectional method
Abstract

Background: Identifying comorbidities that influence preclinical Alzheimer’s disease (AD) can give some insight into the AD early stages trajectories to allow new treatment venues and to guide public health systems to prevent subsequent dementia. Objective: To examine the association of multimorbidity with AD neuroimaging markers in cognitively normal older adults. Methods: This study had a cross-sectional design. Data regarding 14 comorbidities were obtained for all 318 adults aged 70–85 years, recruited from the community to an ongoing prospective monocentric cohort. They underwent standardized neuropsychological and neuroimaging assessment with automated methods that measured hippocampal volumes, white matter hyperintensity volumes, fluorodeoxyglucose positron emission tomography (FDG-PET) standardized uptake values (SUV) in AD signature regions, and amyloid positron emission tomography (amyloid-PET) SUV ratios. Linear regression was used to assess the association of multimorbidity with AD neuroimaging biomarkers. Results: Multimorbidity is signif icantly associated with lower hippocampal volumes (–0.03 ± 0.01; p = 0.012; R2 = 0.017) and lower FDG-PET SUV (–0.027 ± 0.009; p = 0.005; R2 = 0.022), with no association with amyloid deposition (0.001 ± 0.007; p = 0.884; R2 = 0.0001). Taken individually, obesity and excessive alcohol use are associated with lower FDG-PET values, whereas obstructive sleep apnea and mood disorders are related to lower amyloid-PET SUV ratios. Conclusion: Multimorbidity is associated with preclinical AD imaging markers of neurodegeneration, but not with amyloid. [ABSTRACT FROM AUTHOR]

Published
2018
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6. Correction: Applicability of in vivo staging of regional amyloid burden in a cognitively normal cohort with subjective memory complaints: the INSIGHT-preAD study.

Author

Sakr, Fatemah A., Grothe, Michel J., Cavedo, Enrica, Jelistratova, Irina, Habert, Marie-Odile, Dyrba, Martin, Gonzalez-Escamilla, Gabriel, Bertin, Hugo, Locatelli, Maxime, Lehericy, Stephane, Teipel, Stefan, Dubois, Bruno, Hampel, Harald, for the INSIGHT-preAD study group, Bakardjian, Hovagim, Benali, Habib, Bonheur, Joel, Boukadida, Laurie, Boukerrou, Nadia, and Chiesa, Patrizia

Subjects
AMYLOID, MEMORY, INDIVIDUALIZED medicine
Abstract

Fatemah A. Sakr and Michel J. Grothe contributed equally to this work. B Correction: Alz Res Therapy 11, 15 (2019) b B https://doi.org/10.1186/s13195-019-0466-3 b Following the publication of the original article [[1]] the authors reported that members of "Alzheimer Precision Medicine Initiative (APMI)" are not visible in the collaborator list indexed. [Extracted from the article]

Published
2022
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7. Cortical amyloid accumulation is associated with alterations of structural integrity in older people with subjective memory complaints.

Author

Teipel, Stefan J., Cavedo, Enrica, Weschke, Sarah, Grothe, Michel J., Rojkova, Katrine, Fontaine, Gaëlle, Dauphinot, Luce, Gonzalez-Escamilla, Gabriel, Potier, Marie-Claude, Bertin, Hugo, Habert, Marie-Odile, Dubois, Bruno, and Hampel, Harald

Subjects
*MAGNETIC resonance imaging, *AMYLOID, *COGNITION disorders treatment, *COGNITIVE load, *PREFRONTAL cortex, *THERAPEUTICS
Abstract

We determined the effect of cortical amyloid load using 18 F-florbetapir PET on cognitive performance and gray matter structural integrity derived from MRI in 318 cognitively normally performing older people with subjective memory impairment from the INSIGHT-preAD cohort using multivariate partial least squares regression. Amyloid uptake was associated with reduced gray matter structural integrity in hippocampus, entorhinal and cingulate cortex, middle temporal gyrus, prefrontal cortex, and lentiform nucleus ( p < 0.01, permutation test). Higher amyloid load was associated with poorer global cognitive performance, delayed recall and attention ( p < 0.05), independently of its effects on gray matter connectivity. These findings agree with the assumption of a two-stage effect of amyloid on cognition, (1) an early direct effect in the preclinical stages of Alzheimer's disease and (2) a delayed effect mediated by downstream effects of amyloid accumulation, such as gray matter connectivity decline. [ABSTRACT FROM AUTHOR]

Published
2017
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