A1 Refereed original research article in a scientific journal

Associations of lifestyle factors with amyloid pathology in persons without dementia



Authors: Oomens, Julie E.; Vos, Stephanie J. B.; Maserejian, Nancy N.; Boada, Mercè; Didic, Mira; Engelborghs, Sebastiaan; Fladby, Tormod; van der Flier, Wiesje M.; Frisoni, Giovanni B.; Fröhlich, Lutz; Gill, Kiran Dip; Grimmer, Timo; Hort, Jakub; Itoh, Yoshiaki; Iwatsubo, Takeshi; Klimkowicz-Mrowiec, Aleksandra; Landau, Susan M.; Lee, Dong Young; Lleó, Alberto; Martinez-Lage, Pablo; de Mendonça, Alexandre; Meyer, Philipp T.; Parchi, Piero; Pardini, Matteo; Parnetti, Lucilla; Popp, Julius; Rami, Lorena; Reiman, Eric M.; Rinne, Juha O.; Rodrigue, Karen M.; Sánchez-Juan, Pascual; Santana, Isabel; Scarmeas, Nikolaos; Scheltens, Philip; Skoog, Ingmar; Sperling, Reisa A.; Stern, Yaakov; Villeneuve, Sylvia; Waldemar, Gunhild; Wiltfang, Jens; Zetterberg, Henrik; Alcolea, Daniel; Allegri, Ricardo F.; Altomare, Daniele; Bateman, Randall J.; Baiardi, Simone; Baldeiras, Ines; Blennow, Kaj; den Braber, Anouk; van Buchem, Mark A.; Byun, Min Soo; Cerman, Jiří; Chen, Kewei; Chipi, Elena; Day, Gregory S.; Drzezga, Alexander; Ekblad, Laura L.; Förster, Stefan; Fortea, Juan; Freund-Levi, Yvonne; Frings, Lars; Guedj, Eric; Habeck, Christian G.; Handels, Ron; Hausner, Lucrezia; Hellwig, Sabine; Jiménez-Bonilla, Julio F.; Juaristi, Ane Iriondo; Kandimalla, Ramesh; Kern, Silke; Bordewick Kirsebom, Bjørn-Eivind S.; Kornhuber, Johannes; Legdeur, Nienke; Levin, Johannes; Maier, Wolfgang; Marquié, Marta; Minatani, Shinobu; Morbelli, Silvia Daniela; Mroczko, Barbara; Ntanasi, Eva; de Oliveira, Catarina Resende; Orellana, Adelina; Peters, Oliver; Prabhakar, Sudesh; Ramakers, Inez H.; Rodríguez-Rodriguez, Eloy; Ruiz, Agustín; Rüther, Eckart; Sakhardande, Jayant; Selnes, Per; Silva, Dina; Soininen, Hilkka; Spiru, Luiza; Takeda, Akitoshi; Teunissen, Charlotte E.; Tijms, Betty M.; Vermunt, Lisa; Wallin, Åsa K.; Wiels, Wietse; Yannakoulia, Mary; Yi, Dahyun; Zettergren, Anna; Alzheimer's Disease Neuroimaging Initiative (ADNI); A4 Study group; Dominantly Inherited Alzheimer Network (DIAN); European Prevention of Alzheimer's Dementia (EPAD) consortium, Fundació ACE Healthy Brain Initiative (FACEHBI); Japan Alzheimer's Disease Neuroimaging Initiative (J-ADNI), Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease (KBASE); Presymptomatic Evaluation of Experimental or Novel Treatments for Alzheimer's Disease (PREVENT-AD) research group; Ossenkoppele, Rik; Verhey, Frans R. J.; Visser, Pieter Jelle; Jansen, Willemijn J.

Publisher: SAGE Publications

Publication year: 2025

Journal: Journal of Alzheimer's Disease

Article number: 13872877251379083

Volume: 108

Issue: 3

First page : 1043

Last page: 1059

ISSN: 1387-2877

eISSN: 1875-8908

DOI: https://doi.org/10.1177/13872877251379083

Publication's open availability at the time of reporting: Open Access

Publication channel's open availability : Open Access publication channel

Web address : https://doi.org/10.1177/13872877251379083

Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/505396026


Abstract
Background

The association between lifestyle factors and Alzheimer's disease (AD) pathophysiology remains incompletely understood.

Objective

The aim of this study was to assess the association of alcohol consumption, smoking behavior, sleep quality and physical, cognitive, and social activity with cerebral amyloid pathology.

Methods

For this cross-sectional study, we selected participants from the Amyloid Biomarker Study data pooling initiative. We used generalized estimating equations to assess associations of dichotomized lifestyle measures with amyloid pathology.

Results

We included 9171 participants with normal cognition (NC) and 2555 participants with mild cognitive impairment (MCI) from the Amyloid Biomarker Study. Of participants with NC, 58% were women, 34% were APOE ε4 carrier, and 27% had amyloid pathology. Of participants with MCI, 48% were women, 47% were APOE ε4 carrier, and 57% had amyloid pathology. In NC, cognitively active participants were less likely to have amyloid pathology (OR = 0.77, 95%CI 0.66–0.89, p < 0.001). In MCI, participants who had ever smoked or had sleep problems were less likely to have amyloid pathology (OR = 0.85, 95%CI 0.73–0.99, p = 0.029; OR = 0.62, 95%CI 0.45–0.86, p = 0.004).

Conclusions

In NC, cognitive activity was associated with a lower frequency of amyloid pathology. In MCI, favorable lifestyle behaviors were not associated with a lower frequency of amyloid pathology. The results of the current study contribute to the broader evidence base on lifestyle and AD by further characterizing the role of lifestyle behaviors in AD pathology across different clinical stages.


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Funding information in the publication: 
Data used in preparation of the present article were obtained from the ADNI database (adni.loni.usc.edu). As such, ADNI investigators provided and contributed to the design and implementation of the ADNI data but did not participate in the analysis or writing of this article. A complete listing of ADNI investigators can be found at http://adni.loni.usc.edu/wp-content/ uploads/how_to_apply/ADNI_Acknowledgement_ List.pdf. The ADNI was launched in 2003 as a public-private partnership, led by principal investigator Michael W. Weiner, MD. The primary goal of ADNI is to test whether serial magnetic resonance imaging, PET, other biological markers, and clinical and neuropsychological assessment can be combined to measure the progression of mild cognitive impairment and early Alzheimer disease. Data collection and sharing for this project was funded by grant U01 AG024904 from the NIH and award W81XWH-12–2-0012 from the US Department of Defense. 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, 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.
The A4 and Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) studies are led by Dr Sperling at Brigham and Women's Hospital, Harvard Medical School, and by Dr Paul Aisen at the ATRI. The A4 and LEARN studies are coordinated by the ATRI, and the data are made available through the Laboratory for Neuroimaging. The participants screening for the A4 Study provided permission to share their deidentified data to advance the objective to find a successful treatment for Alzheimer disease. The A4 Study is a secondary prevention trial in preclinical Alzheimer disease that aims to slow cognitive decline associated with brain amyloid accumulation in clinically normal older individuals.
A proportion of the data used in preparation of this article was obtained from the following: LEARN study, which was performed within the framework of the Center for Translational Molecular Medicine, a Dutch public-private partnership (project LEARN; grant 02 N-101 from Center for Translational Molecular Medicine); DIAN (grant UF01AG032438 from NIA), which was funded by the NIA, German Center for Neurodegenerative Diseases, Raul Carrea Institute for Neurological Research, and partially by the research and development grants for dementia from Japan Agency for Medical Research and Development and Korea Health Technology Research and Development Project through the Korea Health Industry Development Institute; and PREVENT-AD program (https://douglas.research. mcgill.ca/stop-ad-centre; data release 5.0, November 30, 2017), which provided and contributed to the design and implementation of PREVENT-AD data but did not participate in the analysis or writing of this article. A complete listing of PREVENT-AD research group investigators can be found at http://preventad.loris.ca/ acknowledgements/acknowledgements.php?date = [2020 = 04–01].
Data collection and sharing for this project was supported by The Dominantly Inherited Alzheimer Network (DIAN, U19AG032438) funded by the National Institute on Aging (NIA),the Alzheimer's Association (SG-20-690363-DIAN), the German Center for Neurodegenerative Diseases (DZNE), Raul Carrea Institute for Neurological Research (FLENI), Partial support by the Research and Development Grants for Dementia from Japan Agency for Medical Research and Development, AMED, and the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), Spanish Institute of Health Carlos III (ISCIII), Canadian Institutes of Health Research (CIHR), Canadian Consortium of Neurodegeneration and Aging, Brain Canada Foundation, and Fonds de Recherche du Québec—Santé. This manuscript has been reviewed by DIAN Study investigators for scientific content and consistency of data interpretation with previous DIAN Study publications. We acknowledge the altruism of the participants and their families and contributions of the DIAN research and support staff at each of the participating sites for their contributions to this study.
The FACEHBI study was supported by funds from Fundació ACE Institut Català de Neurociències Aplicades, Grifols, Life Molecular Imaging, Araclon Biotech, Alkahest, Laboratorio de Análisis Echevarne and IrsiCaixa.
The KBASE cohort was funded by the Ministry of Health & Welfare, South Korea (HI18C0630 & HI19C0149), the Ministry of Science and ICT (NRF-2014M3C7A1046042), and the NIA, United States (U01AG072177). The overview of the study can be found at http://kbase.kr/.
Part of the present study was supported by the European Medical Information Framework Alzheimer's Disease (EMIF- AD), which received support from the Innovative Medicines Initiative Joint Undertaking under EMIF-AD grant agreement 115372 that comprised financial contribution from the EU's Seventh Framework Program (FP7/2007-2013) and in kind contribution from EFPIA companies. Research of Alzheimer Centre Amsterdam was part of the neurodegeneration research program of Amsterdam Neuroscience. Alzheimer Centre Amsterdam was supported by Stichting Alzheimer Nederland and Stichting VUmc Fonds. The SCIENCe project was supported by research grants from Gieskes-Strijbis Fonds and Stichting Dioraphte. PET scans in the Amsterdam Dementia Cohort were obtained with research grants from GE Healthcare, Life Molecular Imaging, AVID, and ZonMW- Memorabel, the research and innovation program for dementia.
The Czech Brain Aging Study was supported by project No. LX22NPO5107)—Funded by the European Union—Next Generation EU. Research of Alzheimer center Amsterdam is part of the neurodegeneration research program of Amsterdam Neuroscience. Alzheimer Center Amsterdam is supported by Stichting Alzheimer Nederland and Stichting Steun Alzheimercentrum Amsterdam. The chair, Wiesje van der Flier, is supported by the Pasman stichting.
The Sant Pau Memory Unit received funding from CIBERNED, ISCIII, which is jointly funded by FEDER, EU, Una manera de hacer Europa; Generalitat de Catalunya; Fundació La Marató TV3 Fundació Bancària Obra Social La Caixa; Fundación BBVA; Fundación Española para el Fomento de la Investigación de la Esclerosis Lateral Amiotrófica; Global Brain Health Institute; Fundació Catalana Síndrome de Down; and Fundació Víctor Grífols i Lucas.
The Phoenix Arizona APOE Cohort was funded by grant R01 AG031581 from the NIA. The Imabio3 and Shatau7-Imataustudies (Sarazin,Paris)were supported by grants PHRC-0054-N 2010 and PHRC-2013-0919 from the French Health Ministry, the Institut Roche de Recherche et Medecine Translationelle (Imabio3), Service Hospitalier Frédéric Joliot, Fondation pour la Recherchesur Alzheimer, Institut de Recherches Internationales Servier, and France-Alzheimer (Shatau7-Imatau).
The Nijmegen cohort was supported by the BIONIC project (grant 733050822 from ZonMW- Memorabel as part of the Dutch National Deltaplan for Dementia [zonmw.nl/dementiaresearch]), the CAFÉ project (grant 5R01NS104147-02 from the NIH), and the Selfridges Group Foundation (grant NR170024). The BIONIC project is a consortium of Radboudumc, LUMC, ADX Neurosciences, and Rhode Island University.
A part data used for this research was originally obtained from the Japanese ADNI database. Japanese ADNI is led by Prof Iwatsubo and the databse is available at the website of the NBDC Human Database (https://biosciencedbc.jp/en/) of the Japan Science and Technology Agency (JST).
This work is supported by the Indian Council of Medical Research (ICMR), 52/3/2003, New Delhi, India. Ramesh Kandimalla is a senior research fellow (SRF) from ICMR, New Delhi, India.
HZ is a Wallenberg Scholar and a Distinguished Professor at the Swedish Research Council supported by grants from the Swedish Research Council (#2023-00356; #2022-01018 and #2019-02397), the European Union's Horizon Europe research and innovation programme under grant agreement No 101053962, Swedish State Support for Clinical Research (#ALFGBG-71320), the Alzheimer Drug Discovery Foundation (ADDF), USA (#201809-2016862), the AD Strategic Fund and the Alzheimer's Association (#ADSF-21-831376-C, #ADSF-21-831381-C, #ADSF-21-831377-C, and #ADSF-24-1284328-C), the Bluefield Project, Cure Alzheimer's Fund, the Olav Thon Foundation, the Erling-Persson Family Foundation, Stiftelsen för Gamla Tjänarinnor, Hjärnfonden, Sweden (#FO2022-0270), the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 860197 (MIRIADE), the European Union Joint Programme—Neurodegenerative Disease Research (JPND2021-00694), the National Institute for Health and Care Research University College London Hospitals Biomedical Research Centre, and the UK Dementia Research Institute at UCL (UKDRI-1003).


Last updated on 2025-26-11 at 15:39