TY - JOUR
T1 - Biomarkers and phenotypic expression in Alzheimer’s disease
T2 - exploring the contribution of frailty in the Alzheimer’s Disease Neuroimaging Initiative
AU - for the Alzheimer’s Disease Neuroimaging Initiative
AU - Canevelli, Marco
AU - Arisi, Ivan
AU - Bacigalupo, Ilaria
AU - Arighi, Andrea
AU - Galimberti, Daniela
AU - Vanacore, Nicola
AU - D’Onofrio, Mara
AU - Cesari, Matteo
AU - Bruno, Giuseppe
N1 - Funding Information:
Open access funding provided by Università degli Studi di Roma La Sapienza within the CRUI-CARE Agreement. This study was partially supported by the grant POR (Operative Program Lazio Region, Italy) FESR (European Program Regional Development) 2014 - 2020. Public Notice “LIFE 2020”, MODIAG Project. This work was also supported (in part) by Fondo Ordinario Enti (FOE D.M 865/2019) funds in the framework of a collaboration agreement between the Italian National Research Council and EBRI (2019-2021).
Funding Information:
The authors have no conflicts of interest to disclose for the present study. Marco Canevelli is supported by a research grant of the Italian Ministry of Health (GR-2016-02364975) for the project “Dementia in immigrants and ethnic minorities living in Italy: clinical-epidemiological aspects and public health perspectives” (ImmiDem). Matteo Cesari has received honoraria for presentations at scientific meetings and/or research funding from Nestlé and Pfizer. He is involved in the coordination of an Innovative Medicines Initiative–funded project (including partners from the European Federation Pharmaceutical Industries and Associates [Sanofi, Novartis, Servier, GSK, Lilly]).
Funding Information:
Data collection and sharing for this project was funded by the Alzheimer’s Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, by the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie, Alzheimer’s Association; Alzheimer’s Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health ( www.fnih.org ). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer’s Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California.
Publisher Copyright:
© 2020, The Author(s).
PY - 2021/4
Y1 - 2021/4
N2 - The present study aimed at investigating if the main biomarkers of Alzheimer’s disease (AD) neuropathology and their association with cognitive disturbances and dementia are modified by the individual’s frailty status. We performed a cross-sectional analysis of data from participants with normal cognition, mild cognitive impairment (MCI), and AD dementia enrolled in the Alzheimer’s Disease Neuroimaging Initiative 2 (ADNI2) study. Frailty was operationalized by computing a 40-item Frailty Index (FI). The following AD biomarkers were considered and analyzed according to the participants’ frailty status: CSF Aβ1-42, 181P-tau, and T-tau; MRI-based hippocampus volume; cortical glucose metabolism at the FDG PET imaging; amyloid deposition at the 18F-AV-45 PET imaging. Logistic regression models, adjusted for age, sex, and education, were performed to explore the association of biomarkers with cognitive status at different FI levels. Subjects with higher FI scores had lower CSF levels of Aβ1-42, hippocampus volumes at the MRI, and glucose metabolism at the FDG PET imaging, and a higher amyloid deposition at the 18F-AV-45 PET. No significant differences were observed among the two frailty groups concerning ApoE genotype, CSF T-tau, and P-tau. Increasing frailty levels were associated with a weakened relationship between dementia and 18F-AV-45 uptake and hippocampus volume and with a stronger relationship of dementia with FDG PET. Frailty contributes to the discrepancies between AD pathology and clinical manifestations and influences the association of AD pathological modifications with cognitive changes. AD and dementia should increasingly be conceived as “complex diseases of aging,” determined by multiple, simultaneous, and interacting pathophysiological processes.
AB - The present study aimed at investigating if the main biomarkers of Alzheimer’s disease (AD) neuropathology and their association with cognitive disturbances and dementia are modified by the individual’s frailty status. We performed a cross-sectional analysis of data from participants with normal cognition, mild cognitive impairment (MCI), and AD dementia enrolled in the Alzheimer’s Disease Neuroimaging Initiative 2 (ADNI2) study. Frailty was operationalized by computing a 40-item Frailty Index (FI). The following AD biomarkers were considered and analyzed according to the participants’ frailty status: CSF Aβ1-42, 181P-tau, and T-tau; MRI-based hippocampus volume; cortical glucose metabolism at the FDG PET imaging; amyloid deposition at the 18F-AV-45 PET imaging. Logistic regression models, adjusted for age, sex, and education, were performed to explore the association of biomarkers with cognitive status at different FI levels. Subjects with higher FI scores had lower CSF levels of Aβ1-42, hippocampus volumes at the MRI, and glucose metabolism at the FDG PET imaging, and a higher amyloid deposition at the 18F-AV-45 PET. No significant differences were observed among the two frailty groups concerning ApoE genotype, CSF T-tau, and P-tau. Increasing frailty levels were associated with a weakened relationship between dementia and 18F-AV-45 uptake and hippocampus volume and with a stronger relationship of dementia with FDG PET. Frailty contributes to the discrepancies between AD pathology and clinical manifestations and influences the association of AD pathological modifications with cognitive changes. AD and dementia should increasingly be conceived as “complex diseases of aging,” determined by multiple, simultaneous, and interacting pathophysiological processes.
KW - Aging
KW - Alzheimer’s disease
KW - Biomarkers
KW - Dementia
KW - Frailty
UR - http://www.scopus.com/inward/record.url?scp=85096293852&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85096293852&partnerID=8YFLogxK
U2 - 10.1007/s11357-020-00293-y
DO - 10.1007/s11357-020-00293-y
M3 - Article
C2 - 33210215
AN - SCOPUS:85096293852
VL - 43
SP - 1039
EP - 1051
JO - GeroScience
JF - GeroScience
SN - 2509-2715
IS - 2
ER -