Associations of lifestyle factors with amyloid pathology in persons without dementia

Julie E Oomens¹, Stephanie Jb Vos¹, Nancy N Maserejian², Mercè Boada^{3

4}, Mira Didic^{5

6}, Sebastiaan Engelborghs^{7

8}, Tormod Fladby⁹, Wiesje M van der Flier^{10

11}, Giovanni B Frisoni¹², Lutz Fröhlich¹³, Kiran Dip Gill¹⁴, Timo Grimmer¹⁵, Jakub Hort¹⁶, Yoshiaki Itoh¹⁷, Takeshi Iwatsubo¹⁸, Aleksandra Klimkowicz-Mrowiec¹⁹, Susan M Landau²⁰, Dong Young Lee²¹, Alberto Lleó^{4

22}, Pablo Martinez-Lage²³, Alexandre de Mendonça²⁴, Philipp T Meyer²⁵, Piero Parchi^{26

27}, Matteo Pardini²⁸, Lucilla Parnetti²⁹, Julius Popp^{30

31}, Lorena Rami³², Eric M Reiman³³, Juha O Rinne³⁴, Karen M Rodrigue³⁵, Pascual Sánchez-Juan^{4

36}, Isabel Santana^{37

38

39}, Nikolaos Scarmeas^{40

41}, Philip Scheltens¹⁰, Ingmar Skoog⁴², Reisa A Sperling^{43

44}, Yaakov Stern⁴⁵, Sylvia Villeneuve^{46

47

48}, Gunhild Waldemar^{49

50}, Jens Wiltfang^{51

52}, Henrik Zetterberg^{53

54

55

56

57

58}, Daniel Alcolea^{4

22}, Ricardo F Allegri⁵⁹, Daniele Altomare⁶⁰, Randall J Bateman⁶¹, Simone Baiardi²⁷, Ines Baldeiras^{37

38

39}, Kaj Blennow⁵⁴, Anouk den Braber¹⁰, Mark A van Buchem⁶², Min Soo Byun²¹, Jiří Cerman¹⁶, Kewei Chen³³, Elena Chipi²⁹, Gregory S Day⁶³, Alexander Drzezga⁶⁴, Laura L Ekblad^{34

65}, Stefan Förster^{66

67}, Juan Fortea^{4

22}, Yvonne Freund-Levi^{68

69

70}, Lars Frings²⁵, Eric Guedj⁷¹, Christian G Habeck⁷², Ron Handels¹, Lucrezia Hausner¹³, Sabine Hellwig⁷³, Julio F Jiménez-Bonilla⁷⁴, Ane Iriondo Juaristi²³, Ramesh Kandimalla^{75

76

77}, Silke Kern^{53

78}, Bjørn-Eivind S Bordewick Kirsebom^{79

80}, Johannes Kornhuber⁸¹, Nienke Legdeur¹⁰, Johannes Levin^{82

83

84}, Wolfgang Maier⁸⁵, Marta Marquié^{3

4}, Shinobu Minatani¹⁷, Silvia Daniela Morbelli^{86

87}, Barbara Mroczko^{88

89}, Eva Ntanasi⁹⁰, Catarina Resende de Oliveira³⁸, Adelina Orellana^{3

4}, Oliver Peters⁹¹, Sudesh Prabhakar⁹², Inez H Ramakers¹, Eloy Rodríguez-Rodriguez⁹³, Agustín Ruiz^{3

4}, Eckart Rüther⁹⁴, Jayant Sakhardande⁴⁵, Per Selnes⁹, Dina Silva²⁴, Hilkka Soininen^{95

96}, Luiza Spiru^{97

98}, Akitoshi Takeda¹⁷, Charlotte E Teunissen⁹⁹, Betty M Tijms¹⁰, Lisa Vermunt¹⁰, Åsa K Wallin¹⁰⁰, Wietse Wiels^{101

102}, Mary Yannakoulia⁹⁰, Dahyun Yi¹⁰³, Anna Zettergren⁵³; Alzheimer's Disease Neuroimaging Initiative (ADNI)¹⁰⁴; A4 Study group¹⁰⁴; Dominantly Inherited Alzheimer Network (DIAN)¹⁰⁴; European Prevention of Alzheimer's Dementia (EPAD) consortium, Fundació ACE Healthy Brain Initiative (FACEHBI)¹⁰⁴; Japan Alzheimer's Disease Neuroimaging Initiative (J-ADNI), Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease (KBASE)¹⁰⁴; Presymptomatic Evaluation of Experimental or Novel Treatments for Alzheimer's Disease (PREVENT-AD) research group¹⁰⁴; Rik Ossenkoppele^{10

100}, Frans Rj Verhey¹, Pieter Jelle Visser^{1

10

105}, Willemijn J Jansen^{1

33}

Affiliations

¹ Alzheimer Center Limburg, Department of Psychiatry & Neuropsychology, Mental Health and Neuroscience Research Institute, Maastricht University, Maastricht, the Netherlands.
² Department of Epidemiology, Biogen, Cambridge, MA, USA.
³ Ace Alzheimer Center Barcelona - Universitat Internacional de Catalunya, Barcelona, Spain.
⁴ CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain.
⁵ APHM, Timone, Service de Neurologie et Neuropsychologie, Hôpital Timone Adultes, Marseille, France.
⁶ Aix Marseille Univ, INSERM, INS, Inst Neurosci Syst, Jardin du Pharo, Marseille, France.
⁷ Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.
⁸ NEUR Research Group, Center for Neurosciences, Vrije Universiteit Brussel, Brussels, Belgium.
⁹ Department of Neurology, Akershus University Hospital, Lorenskog, Norway.
¹⁰ Department of Neurology, Alzheimer Centre Amsterdam, Amsterdam Neuroscience, Amsterdam UMC location VUmc, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
¹¹ Epidemiology and Data Science, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc, Amsterdam, the Netherlands.
¹² Memory Clinic, University Hospitals and University of Geneva, Geneva, Switzerland.
¹³ Department of Geriatric Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
¹⁴ Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
¹⁵ Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, Technical University of Munich (TUM), School of Medicine and Health, Munich, Germany.
¹⁶ Department of Neurology, Second Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic.
¹⁷ Department of Neurology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan.
¹⁸ Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Tokyo, Japan.
¹⁹ Department of Internal Medicine and Gerontology, Faculty of Medicine, Jagiellonian University Medical College, Krakow, Poland.
²⁰ Helen Wills Neuroscience Institute, University of California, Berkeley, CA, USA.
²¹ Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea.
²² Memory Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
²³ Center for Research and Advanced Therapies, CITA-Alzheimer Foundation, Donostia-San Sebastian, Spain.
²⁴ Faculty of Medicine, University of Lisbon, Lisboa, Portugal.
²⁵ Department of Nuclear Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
²⁶ Istituto delle Scienze Neurologiche di Bologna, IRCCS, Padiglione G, Bologna, Italy.
²⁷ Department of Biomedical and Neuromotor Sciences (DiBiNeM), University of Bologna, Bologna, Italy.
²⁸ DINOGMI, University of Genoa, Genoa, Italy.
²⁹ Centro Disturbi della Memoria, Laboratorio di Neurochimica Clinica, Clinica Neurologica, Università di Perugia, Perugia, Italy.
³⁰ Department of Geriatric Psychiatry, University Hospital of Psychiatry Zürich and University of Zürich, Zürich, Switzerland.
³¹ Old Age Psychiatry, Department of Psychiatry, University Hospital of Lausanne and University of Lausanne, Lausanne, Switzerland.
³² Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic of Barcelona, IDIBAPS, Barcelona, Spain.
³³ Banner Alzheimer's Institute, Phoenix, AZ, USA.
³⁴ Turku PET Centre, University of Turku, Turku, Finland.
³⁵ Center for Vital Longevity, School of Behavioral and Brain Sciences, The University of Texas at Dallas, Richardson, TX, USA.
³⁶ Alzheimer's Centre Reina Sofia-CIEN Foundation-ISCIII, Madrid, Spain.
³⁷ Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
³⁸ Center for Neuroscience and Cell Biology - CIBB, University of Coimbra, Coimbra, Portugal.
³⁹ Neurology Department and Laboratory of Neurochemistry, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.
⁴⁰ 1st Department of Neurology, Aiginition Hospital, National and Kapodistrian University of Athens, Medical School, Athens, Greece.
⁴¹ Department of Neurology, Columbia University, New York City, NY, USA.
⁴² Neuropsychiatric Epidemiology Unit, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
⁴³ Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
⁴⁴ Harvard Aging Brain Study, Department of Neurology, Harvard Medical School, Boston, MA, USA.
⁴⁵ Cognitive Neuroscience Division, Department of Neurology and the Taub Institute, Columbia, New York City, NY, USA.
⁴⁶ McConnell Brain Imaging Centre, Montreal Neurological Institute, Montreal, Quebec, Canada.
⁴⁷ Department of Psychiatry, Faculty of Medicine, McGill University, Montreal, Quebec, Canada.
⁴⁸ Douglas Mental Health University Institute, Montreal, Quebec, Canada.
⁴⁹ Danish Dementia Research Center, Department of Neurology, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.
⁵⁰ Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
⁵¹ Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Göttingen, Germany.
⁵² Center of Neurology, Department of Neurodegeneration and Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
⁵³ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
⁵⁴ Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
⁵⁵ Department of Neurodegenerative Disease, University College London Queen Square Institute of Neurology, London, UK.
⁵⁶ UK Dementia Research Institute, London, UK.
⁵⁷ Hong Kong Center for Neurodegenerative Diseases, Hongkong, China.
⁵⁸ Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.
⁵⁹ Department of Cognitive Neurology, Instituto Neurológico Fleni, Buenos Aires, Argentina.
⁶⁰ Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
⁶¹ Department of Neurology and the Alzheimer's Disease Research Center, Washington University School of Medicine, St Louis, MO, USA.
⁶² Department of Radiology, University Medical Center Leiden is the institution, Leiden, the Netherlands.
⁶³ Department of Neurology, Mayo Clinic in Florida, Jacksonville, FL, USA.
⁶⁴ Department of Nuclear Medicine, University Hospital of Cologne, Cologne, Germany.
⁶⁵ Department of Geriatrics, Turku University Hospital, Wellbeing services county of Southwestern Finland, Turku, Finland.
⁶⁶ Department of Nuclear Medicine, Klinikum rechts der Isar, Technical University of Munich (TUM), Munich, Germany.
⁶⁷ Department of Nuclear Medicine, Klinikum Bayreuth, Bayreuth, Germany.
⁶⁸ School of Medical Sciences, Örebro University, Örebro, Sweden.
⁶⁹ Department of Neurobiology, Care Sciences and Society, Division of Clinical Geriatrics, Karolinska Institutet Center for Alzheimer Research, Stockholm, Sweden.
⁷⁰ Department of Old Age Psychiatry, Psychology and Neuroscience, King's College, London, UK.
⁷¹ Nuclear Medicine Department, Aix Marseille University, AP-HM, CNRS, Centrale Marseille, Institut Fresnel, Timone Hospital, Centre Européen de Recherche en Imagerie Médicale (CERIMED), Marseille, France.
⁷² Department of Neurology, Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Irving Medical Center, New York, NY, USA.
⁷³ Department of Psychiatry and Psychotherapy Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
⁷⁴ Department of Nuclear Medicine, Marqués de Valdecilla University Hospital and IDIVAL, Santander, Spain.
⁷⁵ Department of Radiation Oncology, Emory University, Atlanta, GA, USA.
⁷⁶ Applied Biology, Council of Scientific and Industrial Research (CSIR)-Indian Institute of Chemical Technology, Hyderabad, Telangana State, India.
⁷⁷ Department of Biochemistry, Kakatiya Medical College/Mahatma Gandhi Memorial Hospital, Warangal, Telangana State, India.
⁷⁸ Department of Psychiatry, Cognition and Old Age Psychiatry, Sahlgrenska University Hospital, Västra Götalandsregion, Sweden.
⁷⁹ Department of Neurology, University Hospital of North Norway, Tromsø, Norway.
⁸⁰ Department of Psychology, The Arctic University of Norway, Tromsø, Norway.
⁸¹ Department of Psychiatry and Psychotherapy, University Hospital, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany.
⁸² Department of Neurology, LMU University Hospital, LMU Munich, Munich, Germany.
⁸³ German Center for Neurodegenerative Diseases, site Munich, Munich, Germany.
⁸⁴ Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
⁸⁵ Department of Neurodegenerative Diseases and Geriatric Psychiatry, University of Bonn, Bonn, Germany.
⁸⁶ Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy.
⁸⁷ Ospedale Policlinico San Martino, IRCCS, Genoa, Italy.
⁸⁸ Department of Neurodegeneration Diagnostics, Medical University of Białystok, Białystok, Poland.
⁸⁹ Department of Biochemical Diagnostics, University Hospital of Białystok, Białystok, Poland.
⁹⁰ Department of Nutrition and Diatetics, Harokopio University, Kallithea, Athens, Greece.
⁹¹ Charité Universitätsmedizin Berlin-CBF, Berlin, Germany.
⁹² Department of Neurology, Nehru Hospital, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
⁹³ Neurology Department, Hospital Universitario Marqués de Valdecilla and IDIVAL, University of Cantabria, Santander, CIBERNED, Madrid, Santander, Spain.
⁹⁴ Department of Psychiatry and Psychotherapy, University Medical Center, Georg-August University, Göttingen, Germany.
⁹⁵ Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.
⁹⁶ Neurocenter, Department of Neurology, Kuopio University Hospital, Kuopia, Finland.
⁹⁷ Geriatrics, Gerontology, Old Age Psychiatry, Geroscience, Gerontechnology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.
⁹⁸ Excellence Center for Memory Diseases, Brain Health and Longevity Medicine - Ana Aslan International Foundation, Bucharest, Romania.
⁹⁹ Neurochemistry Lab, Department of Laboratory Medicine, Amsterdam Neuroscience, Amsterdam UMC location VUmc, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
¹⁰⁰ Cognitive disorder research unit, Department of Clinical Sciences, Lund University, Malmö, Sweden.
¹⁰¹ Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Brussels, Belgium.
¹⁰² Department of Neurology, OLV Hospital, Aalst, Belgium.
¹⁰³ Institute of Human Behavioral Medicine, Medical Research Center Seoul National University, Seoul, Republic of Korea.
¹⁰⁴ Membership detailed in online Appendix 1.
¹⁰⁵ Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.

PMID: 41234025
PMCID: PMC12647378
DOI: 10.1177/13872877251379083

Associations of lifestyle factors with amyloid pathology in persons without dementia

Julie E Oomens et al. J Alzheimers Dis. 2025 Dec.

. 2025 Dec;108(3):1043-1059.

doi: 10.1177/13872877251379083. Epub 2025 Nov 13.

Authors

Affiliations

¹ Alzheimer Center Limburg, Department of Psychiatry & Neuropsychology, Mental Health and Neuroscience Research Institute, Maastricht University, Maastricht, the Netherlands.
² Department of Epidemiology, Biogen, Cambridge, MA, USA.
³ Ace Alzheimer Center Barcelona - Universitat Internacional de Catalunya, Barcelona, Spain.
⁴ CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain.
⁵ APHM, Timone, Service de Neurologie et Neuropsychologie, Hôpital Timone Adultes, Marseille, France.
⁶ Aix Marseille Univ, INSERM, INS, Inst Neurosci Syst, Jardin du Pharo, Marseille, France.
⁷ Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.
⁸ NEUR Research Group, Center for Neurosciences, Vrije Universiteit Brussel, Brussels, Belgium.
⁹ Department of Neurology, Akershus University Hospital, Lorenskog, Norway.
¹⁰ Department of Neurology, Alzheimer Centre Amsterdam, Amsterdam Neuroscience, Amsterdam UMC location VUmc, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
¹¹ Epidemiology and Data Science, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc, Amsterdam, the Netherlands.
¹² Memory Clinic, University Hospitals and University of Geneva, Geneva, Switzerland.
¹³ Department of Geriatric Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
¹⁴ Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
¹⁵ Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, Technical University of Munich (TUM), School of Medicine and Health, Munich, Germany.
¹⁶ Department of Neurology, Second Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic.
¹⁷ Department of Neurology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan.
¹⁸ Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Tokyo, Japan.
¹⁹ Department of Internal Medicine and Gerontology, Faculty of Medicine, Jagiellonian University Medical College, Krakow, Poland.
²⁰ Helen Wills Neuroscience Institute, University of California, Berkeley, CA, USA.
²¹ Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea.
²² Memory Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
²³ Center for Research and Advanced Therapies, CITA-Alzheimer Foundation, Donostia-San Sebastian, Spain.
²⁴ Faculty of Medicine, University of Lisbon, Lisboa, Portugal.
²⁵ Department of Nuclear Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
²⁶ Istituto delle Scienze Neurologiche di Bologna, IRCCS, Padiglione G, Bologna, Italy.
²⁷ Department of Biomedical and Neuromotor Sciences (DiBiNeM), University of Bologna, Bologna, Italy.
²⁸ DINOGMI, University of Genoa, Genoa, Italy.
²⁹ Centro Disturbi della Memoria, Laboratorio di Neurochimica Clinica, Clinica Neurologica, Università di Perugia, Perugia, Italy.
³⁰ Department of Geriatric Psychiatry, University Hospital of Psychiatry Zürich and University of Zürich, Zürich, Switzerland.
³¹ Old Age Psychiatry, Department of Psychiatry, University Hospital of Lausanne and University of Lausanne, Lausanne, Switzerland.
³² Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic of Barcelona, IDIBAPS, Barcelona, Spain.
³³ Banner Alzheimer's Institute, Phoenix, AZ, USA.
³⁴ Turku PET Centre, University of Turku, Turku, Finland.
³⁵ Center for Vital Longevity, School of Behavioral and Brain Sciences, The University of Texas at Dallas, Richardson, TX, USA.
³⁶ Alzheimer's Centre Reina Sofia-CIEN Foundation-ISCIII, Madrid, Spain.
³⁷ Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
³⁸ Center for Neuroscience and Cell Biology - CIBB, University of Coimbra, Coimbra, Portugal.
³⁹ Neurology Department and Laboratory of Neurochemistry, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.
⁴⁰ 1st Department of Neurology, Aiginition Hospital, National and Kapodistrian University of Athens, Medical School, Athens, Greece.
⁴¹ Department of Neurology, Columbia University, New York City, NY, USA.
⁴² Neuropsychiatric Epidemiology Unit, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
⁴³ Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
⁴⁴ Harvard Aging Brain Study, Department of Neurology, Harvard Medical School, Boston, MA, USA.
⁴⁵ Cognitive Neuroscience Division, Department of Neurology and the Taub Institute, Columbia, New York City, NY, USA.
⁴⁶ McConnell Brain Imaging Centre, Montreal Neurological Institute, Montreal, Quebec, Canada.
⁴⁷ Department of Psychiatry, Faculty of Medicine, McGill University, Montreal, Quebec, Canada.
⁴⁸ Douglas Mental Health University Institute, Montreal, Quebec, Canada.
⁴⁹ Danish Dementia Research Center, Department of Neurology, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.
⁵⁰ Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
⁵¹ Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Göttingen, Germany.
⁵² Center of Neurology, Department of Neurodegeneration and Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
⁵³ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
⁵⁴ Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
⁵⁵ Department of Neurodegenerative Disease, University College London Queen Square Institute of Neurology, London, UK.
⁵⁶ UK Dementia Research Institute, London, UK.
⁵⁷ Hong Kong Center for Neurodegenerative Diseases, Hongkong, China.
⁵⁸ Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.
⁵⁹ Department of Cognitive Neurology, Instituto Neurológico Fleni, Buenos Aires, Argentina.
⁶⁰ Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
⁶¹ Department of Neurology and the Alzheimer's Disease Research Center, Washington University School of Medicine, St Louis, MO, USA.
⁶² Department of Radiology, University Medical Center Leiden is the institution, Leiden, the Netherlands.
⁶³ Department of Neurology, Mayo Clinic in Florida, Jacksonville, FL, USA.
⁶⁴ Department of Nuclear Medicine, University Hospital of Cologne, Cologne, Germany.
⁶⁵ Department of Geriatrics, Turku University Hospital, Wellbeing services county of Southwestern Finland, Turku, Finland.
⁶⁶ Department of Nuclear Medicine, Klinikum rechts der Isar, Technical University of Munich (TUM), Munich, Germany.
⁶⁷ Department of Nuclear Medicine, Klinikum Bayreuth, Bayreuth, Germany.
⁶⁸ School of Medical Sciences, Örebro University, Örebro, Sweden.
⁶⁹ Department of Neurobiology, Care Sciences and Society, Division of Clinical Geriatrics, Karolinska Institutet Center for Alzheimer Research, Stockholm, Sweden.
⁷⁰ Department of Old Age Psychiatry, Psychology and Neuroscience, King's College, London, UK.
⁷¹ Nuclear Medicine Department, Aix Marseille University, AP-HM, CNRS, Centrale Marseille, Institut Fresnel, Timone Hospital, Centre Européen de Recherche en Imagerie Médicale (CERIMED), Marseille, France.
⁷² Department of Neurology, Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Irving Medical Center, New York, NY, USA.
⁷³ Department of Psychiatry and Psychotherapy Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
⁷⁴ Department of Nuclear Medicine, Marqués de Valdecilla University Hospital and IDIVAL, Santander, Spain.
⁷⁵ Department of Radiation Oncology, Emory University, Atlanta, GA, USA.
⁷⁶ Applied Biology, Council of Scientific and Industrial Research (CSIR)-Indian Institute of Chemical Technology, Hyderabad, Telangana State, India.
⁷⁷ Department of Biochemistry, Kakatiya Medical College/Mahatma Gandhi Memorial Hospital, Warangal, Telangana State, India.
⁷⁸ Department of Psychiatry, Cognition and Old Age Psychiatry, Sahlgrenska University Hospital, Västra Götalandsregion, Sweden.
⁷⁹ Department of Neurology, University Hospital of North Norway, Tromsø, Norway.
⁸⁰ Department of Psychology, The Arctic University of Norway, Tromsø, Norway.
⁸¹ Department of Psychiatry and Psychotherapy, University Hospital, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany.
⁸² Department of Neurology, LMU University Hospital, LMU Munich, Munich, Germany.
⁸³ German Center for Neurodegenerative Diseases, site Munich, Munich, Germany.
⁸⁴ Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
⁸⁵ Department of Neurodegenerative Diseases and Geriatric Psychiatry, University of Bonn, Bonn, Germany.
⁸⁶ Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy.
⁸⁷ Ospedale Policlinico San Martino, IRCCS, Genoa, Italy.
⁸⁸ Department of Neurodegeneration Diagnostics, Medical University of Białystok, Białystok, Poland.
⁸⁹ Department of Biochemical Diagnostics, University Hospital of Białystok, Białystok, Poland.
⁹⁰ Department of Nutrition and Diatetics, Harokopio University, Kallithea, Athens, Greece.
⁹¹ Charité Universitätsmedizin Berlin-CBF, Berlin, Germany.
⁹² Department of Neurology, Nehru Hospital, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
⁹³ Neurology Department, Hospital Universitario Marqués de Valdecilla and IDIVAL, University of Cantabria, Santander, CIBERNED, Madrid, Santander, Spain.
⁹⁴ Department of Psychiatry and Psychotherapy, University Medical Center, Georg-August University, Göttingen, Germany.
⁹⁵ Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.
⁹⁶ Neurocenter, Department of Neurology, Kuopio University Hospital, Kuopia, Finland.
⁹⁷ Geriatrics, Gerontology, Old Age Psychiatry, Geroscience, Gerontechnology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.
⁹⁸ Excellence Center for Memory Diseases, Brain Health and Longevity Medicine - Ana Aslan International Foundation, Bucharest, Romania.
⁹⁹ Neurochemistry Lab, Department of Laboratory Medicine, Amsterdam Neuroscience, Amsterdam UMC location VUmc, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
¹⁰⁰ Cognitive disorder research unit, Department of Clinical Sciences, Lund University, Malmö, Sweden.
¹⁰¹ Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Brussels, Belgium.
¹⁰² Department of Neurology, OLV Hospital, Aalst, Belgium.
¹⁰³ Institute of Human Behavioral Medicine, Medical Research Center Seoul National University, Seoul, Republic of Korea.
¹⁰⁴ Membership detailed in online Appendix 1.
¹⁰⁵ Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.

PMID: 41234025
PMCID: PMC12647378
DOI: 10.1177/13872877251379083

Abstract

BackgroundThe association between lifestyle factors and Alzheimer's disease (AD) pathophysiology remains incompletely understood.ObjectiveThe 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.MethodsFor 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.ResultsWe 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).ConclusionsIn 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.

Keywords: Alzheimer's disease; amyloid; amyloid biomarker study; cerebrospinal fluid; lifestyle; positron emission tomography.

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Conflict of interest statement

Declaration of conflicting interestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr Alcolea reported participating in advisory boards from Fujirebio-Europe and Roche Diagnostics; receiving speaker honoraria from Fujirebio-Europe, Roche Diagnostics, Nutricia, Krka Farmacéutica SL, Zambon SAU, and Esteve Pharmaceuticals SA; and filing a patent application (WO2019175379 A1 Markers of Synaptopathy in Neurodegenerative Disease).Dr Altomare received funding by the Fondation Recherche Alzheimer, and the Swiss National Science Foundation (project CRSK-3_196354 / 1).Dr Boada reported funding from the Instituto de Salud Carlos III (ISCIII) Acción Estratégica en Salud, integrated in the Spanish National RCDCI Plan and financed by ISCIII-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER—Una manera de hacer Europa) grant PI17/01474; consulting for for Araclon, Avid, Grifols, Lilly, Nutricia, Roche, Eisai and Servier, receiving fees from lectures and funds for research from Araclon, Biogen, Grifols, Nutricia, Roche and Servier and grants/research funding from Abbvie, Araclon, Biogen Research Limited, Bioiberica, Grifols, Lilly, S.A, Merck Sharp & Dohme, Kyowa Hakko Kirin, Laboratorios Servier, Nutricia SRL, Oryzon Genomics, Piramal Imaging Limited, Roche Pharma SA, and Schwabe Farma Iberica SLU.Dr Engelborghs reported participating in consultancy or on advisory boards of Biogen, Danone, Eisai Inc, Icometrix, Pfizer, Novartis, and Roche, and receiving unrestricted research grants (paid to institution) from ADx Neurosciences and Janssen Pharmaceutica.Dr van der Flier reports research programs have been funded by ZonMW, NWO, EU-JPND, Alzheimer Nederland, Hersenstichting CardioVascular Onderzoek Nederland, Health∼Holland, Topsector Life Sciences & Health, stichting Dioraphte, Gieskes-Strijbis fonds, stichting Equilibrio, Edwin Bouw fonds, Pasman stichting, stichting Alzheimer & Neuropsychiatrie Foundation, Philips, Biogen MA Inc, Novartis-NL, Life-MI, AVID, Roche BV, Fujifilm, Eisai, Combinostics. WF holds the Pasman chair. She is recipient of ABOARD, which is a public-private partnership receiving funding from ZonMW (#73305095007) and Health∼Holland, Topsector Life Sciences & Health (PPP-allowance; #LSHM20106). All funding is paid to her institution. She has been an invited speaker at Biogen MA Inc, Danone, Eisai, WebMD Neurology (Medscape), NovoNordisk, Springer Healthcare, NovoNordisk, European Brain Council. All funding is paid to her institution. She is consultant to Oxford Health Policy Forum CIC, Roche, Biogen MA Inc, and Eisai. All funding is paid to her institution. She participated in advisory boards of Biogen MA Inc, Roche, and Eli Lilly. All funding is paid to her institution. She is a member of the steering committee of PAVE, and Think Brain Health. She was associate editor of Alzheimer, Research & Therapy in 2020/2021. WF is associate editor at Brain.Dr Grimmer reported receiving consulting fees from AbbVie, Alector, Anavex, Biogen, BMS; Cogthera, Eli Lilly, Functional Neuromodulation, Grifols, Iqvia, Janssen, Noselab, Novo Nordisk, NuiCare, Orphanzyme, Roche Diagnostics, Roche Pharma, UCB, and Vivoryon; lecture fees from Biogen, Eisai, Grifols, Medical Tribune, Novo Nordisk, Roche Pharma, Schwabe, and Synlab; and has received grants to his institution from Biogen, Eisai, and Roche Diagnostics.Dr Guedj reported having a scientific collaboration on amyloid positron emission tomography (PET) imaging with Life Molecular Imaging before 2018, and honorarium from General Electric and Life Molecular Imaging for expertise and training in the last 3 years.Dr Hort has consulted Eisai, Biogen, Eli Lilly, Roche and Neurona lab and holds stock options in Alzheon company.Dr Jiménez-Bonilla reports receiving the Investigative IDIVAL grant: INNVAL-21-15.Dr Kern reported honorarium for consulting for Geras Solutions and Biogen and Bioarctic.Dr Levin reports speaker fees from Bayer Vital, Biogen, EISAI, TEVA, Zambon, Esteve, Merck and Roche, consulting fees from Axon Neuroscience, EISAI and Biogen, author fees from Thieme medical publishers and W. Kohlhammer GmbH medical publishers and is inventor in a patent “Oral Phenylbutyrate for Treatment of Human 4-Repeat Tauopathies” (PCT/EP2024/053388) filed by LMU Munich. In addition, he reports compensation for serving as chief medical officer for MODAG GmbH, is beneficiary of the phantom share program of MODAG GmbH and is inventor in a patent “Pharmaceutical Composition and Methods of Use” (EP 22 159 408.8) filed by MODAG GmbH, all activities outside the submitted work.Dr Marquié reported funding from the Instituto de Salud Carlos III (ISCIII) Acción Estratégica en Salud, integrated in the Spanish National RCDCI Plan and financed by ISCIII-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER—Una manera de hacer Europa) grant PI19/00335, consulting for F. Hoffmann-La Roche Ltd and participating in advisory boards from Araclon Biotech-Grifols.Dr Maserejian is an employee and shareholder of Biogen, Inc.Dr Mroczko has received consultation and/or lecture honoraria from Abbott, Wiener, Roche, Cormay, Biameditek, and TK Biotech companies.Dr Nobili reported receiving fees for teaching courses from GE Healthcare and Biogen, for advisory board participation from Roche and Biogen, and for consultation from Bial.Dr Ossenkoppele has received research funding from European Research Council, ZonMw, NWO, National Institute of Health, Alzheimer Association, Alzheimer Nederland, Stichting Dioraphte, Cure Alzheimer's fund, Health Holland, ERA PerMed, Alzheimerfonden, Hjarnfonden (all paid to the institutions).R.O. has received research support from Avid Radiopharmaceuticals, Janssen Research & Development, Roche, Quanterix and Optina Diagnostics, and has given lectures in symposia sponsored by GE Healthcare. He is an advisory board member for Asceneuron and Bristol Myers Squibb. All the aforementioned has been paid to the institutions. He is an editorial board member of Alzheimer's Research & Therapy and the European Journal of Nuclear Medicine and Molecular Imaging.Dr Popp reported receiving consultation and speaker honoraria from Nestle Institute of Health Sciences, Innovation Campus, EPFL, Ono Pharma, OM Pharma Suisse, and Fujirebio Europe.Dr Rami reported funding from the Instituto de Salud Carlos III (ISCIII) Acción Estratégica en Salud, integrated in the Spanish National RCDCI Plan and financed by ISCIII-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER—Una manera de hacer Europa) grant PI19/00745.Dr Ruiz reported receiving support from Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III (ISCIII); the EU/European Federation of Pharmaceutical Industries and Associations (EFPIA) Innovative Medicines Initiative Joint Undertaking; grants from the EXIT (Exosomes Isolation Tool with Nanofluidic Concentration Device) project, EU Euronanomed3 Program, and PREADAPT project; grant from the Joint Program for Neurodegenerative Diseases; and research funding from ISCIII Acción Estratégica en Salud, which was integrated in the Spanish National RCDCI Plan and financed by a grant from ISCIII-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER; Una manera de hacer Europa) by Fundación Bancaria La Caixa and Grífols SA (GR@ACE project).Dr Scarmeas reported being a local recruiting site PI for an industry (NovoNordisc) funded multinational, multicenter industry sponsored phase III treatment trial for Alzheimer's disease—funding to institution.Dr Snyder reported being a consultant to Alzheon Inc, AlzeCure Pharma, and AlzPATH Inc outside the submitted work.Dr Soininen reported receiving personal consultation fees from AC Immune and Novo Nordisk outside the submitted work.Dr Sperling reported receiving honorarium for consulting from AC Immune, Acumen, Alnylam, Cytox, Genentech, Janssen, JOMDD, Oligomerix, Neuraly, Neurocentria, Renew, Prothena, and Shionogi; reported receiving research funding from the National Institute on Aging (NIA), Alzheimer's Association, Eisai Inc, Eli Lilly and Company, and Janssen; and reported the following financial relationships for her spouse (Dr Keith Johnson): Cerveau, Janssen, AC Immune, and Novartis.Dr Teunissen reported receiving research support from the European Commission (Marie Curie International Training Network and Joint Program for Neurodegenerative Diseases grants), Health Holland, the Dutch Research Council (ZonMW), Alzheimer Drug Discovery Foundation, The Selfridges Group Foundation, Alzheimer Netherlands, Alzheimer Association, and ABOARD (A Personalized Medicine Approach for Alzheimer's Disease), which is a public-private partnership supported by ZonMW, Alzheimer Nederland, Health Holland, Gieskes-Strijbisfonds, and Edwin Bouw Fonds; having a collaboration contract with ADx Neurosciences, Quanterix, and Eli Lilly and Company; performing contract research or receiving grants from AC Immune, Axon Neurosciences, Biogen, Brainstorm Therapeutics, Celgene, EIP Pharma, Eisai Inc, PeopleBio, Roche, Toyama, and Vivoryon; serving on editorial boards of Medidact Neurologie/ Springer, Alzheimer Research and Therapy, and Neurology: Neuroimmunology & Neuroinflammation; and being editor of a neuromethods book from Springer.Dr Zetterberg reported having served at scientific advisory boards and/or as a consultant for Abbvie, Acumen, Alector, Alzinova, ALZPath, Annexon, Apellis, Artery Therapeutics, AZTherapies, Cognito Therapeutics, CogRx, Denali, Eisai, Nervgen, Novo Nordisk, Optoceutics, Passage Bio, Pinteon Therapeutics, Prothena, Red Abbey Labs, reMYND, Roche, Samumed, Siemens Healthineers, Triplet Therapeutics, and Wave, has given lectures in symposia sponsored by Alzecure, Biogen, Cellectricon, Fujirebio, Lilly, and Roche, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (outside submitted work).Dr Scheltens is a full-time employee of EQT Life Sciences (formerly LSP) and Professor Emeritus at Amsterdam University Medical Centers. He has received consultancy fees (paid to the university) from Alzheon, Brainstorm Cell and Green Valley. Within his university affiliation he was global PI of the phase 1b study of AC Immune, Phase 2b study with FUJI-film/Toyama and phase 2 study of UCB. He is past chair of the EU steering committee of the phase 2b program of Vivoryon and the phase 2b study of Novartis Cardiology and presently co-chair of the phase 3 study with NOVO-Nordisk.Sebastiaan Engelborghs, Matteo Pardini, Yaakov Stern, Henrik Zetterberg, and Ines Baldeiras are Editorial Board Members of this journal but were not involved in the peer-review process of this article nor had access to any information regarding its peer-review.The remaining authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Dr Jansen reported funding from ZonMw, Alzheimer Nederland, St. Rinsum-Ponssen and research support from Biogen (paid to institution).

Figures

**Figure 1.**
Odds ratios for amyloid pathology by cognitive group and lifestyle factor (top: NC, bottom: MCI).

**Figure 2.**
Association between smoking units per week and amyloid pathology in participants with NC.

See this image and copyright information in PMC

References

1. Livingston G, Huntley J, Liu KY, et al. Dementia prevention, intervention, and care: 2024 report of the lancet standing commission. Lancet 2024; 404: 572–628. - PubMed
1. Carvalho DZ, Louis S, Knopman EK, , et al. Association of excessive daytime sleepiness with longitudinal beta-amyloid accumulation in elderly persons without dementia. JAMA Neurol 2018; 75: 672–680. - PMC - PubMed
1. Choe YM, Byun MS, Yi D, et al. Sleep experiences during different lifetime periods and in vivo Alzheimer pathologies. Alzheimers Res Ther 2019; 11: 79. - PMC - PubMed
1. Sprecher KE, Bendlin BB, Racine AM, et al. Amyloid burden is associated with self-reported sleep in nondemented late middle-aged adults. Neurobiol Aging 2015; 36: 2568–2576. - PMC - PubMed
1. Reijs BLR, Vos SJB, Soininen H, et al. Association between later life lifestyle factors and Alzheimer's disease biomarkers in non-demented individuals: a longitudinal descriptive cohort study. J Alzheimers Dis 2017; 60: 1387–1395. - PubMed

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Associations of lifestyle factors with amyloid pathology in persons without dementia

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Associations of lifestyle factors with amyloid pathology in persons without dementia

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