Relationship between physical activity, cognition, and Alzheimer pathology in autosomal dominant Alzheimer's disease

Stephan Müller; Oliver Preische; Hamid R Sohrabi; Susanne Gräber; Mathias Jucker; John M Ringman; Ralph N Martins; Eric McDade; Peter R Schofield; Bernardino Ghetti; Martin Rossor; Nick N Fox; Neill R Graff-Radford; Johannes Levin; Adrian Danek; Jonathan Vöglein; Stephen Salloway; Chengjie Xiong; Tammie Benzinger; Virginia Buckles; Colin L Masters; Reisa Sperling; Randall J Bateman; John C Morris; Christoph Laske; Dominantly Inherited Alzheimer Network (DIAN)

doi:10.1016/j.jalz.2018.06.3059

Relationship between physical activity, cognition, and Alzheimer pathology in autosomal dominant Alzheimer's disease

Alzheimers Dement. 2018 Nov;14(11):1427-1437. doi: 10.1016/j.jalz.2018.06.3059. Epub 2018 Sep 25.

Authors

Stephan Müller¹, Oliver Preische², Hamid R Sohrabi³, Susanne Gräber⁴, Mathias Jucker⁵, John M Ringman⁶, Ralph N Martins³, Eric McDade⁷, Peter R Schofield⁸, Bernardino Ghetti⁹, Martin Rossor¹⁰, Nick N Fox¹⁰, Neill R Graff-Radford¹¹, Johannes Levin¹², Adrian Danek¹², Jonathan Vöglein¹², Stephen Salloway¹³, Chengjie Xiong¹⁴, Tammie Benzinger¹⁵, Virginia Buckles¹⁵, Colin L Masters¹⁶, Reisa Sperling¹⁷, Randall J Bateman¹⁵, John C Morris¹⁵, Christoph Laske⁴; Dominantly Inherited Alzheimer Network (DIAN)

Affiliations

¹ Section for Dementia Research, Department of Cellular Neurology, Hertie Institute for Clinical Brain Research and Department of Psychiatry and Psychotherapy, University of Tübingen, Tübingen, Germany. Electronic address: stephan.mueller@med.uni-tuebingen.de.
² Department of Psychiatry and Psychotherapy, University of Tübingen, Tübingen, Germany; German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
³ Centre of Excellence for Alzheimer's Disease Research and Care, School of Medical and Health Sciences, Edith Cowan University, Perth, Australia; Department of Biomedical Sciences, Macquarie University, Sydney, NSW, Australia.
⁴ Section for Dementia Research, Department of Cellular Neurology, Hertie Institute for Clinical Brain Research and Department of Psychiatry and Psychotherapy, University of Tübingen, Tübingen, Germany; German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
⁵ German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany; Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
⁶ Memory and Aging Center, Keck School of Medicine of USC, Los Angeles, CA, USA.
⁷ University of Pittsburgh School of Medicine, Department of Neurology, Pittsburgh, PA, USA.
⁸ Neuroscience Research Australia, Randwick, Sydney, NSW, Australia; School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia.
⁹ Department of Pathology and Laboratory Medicine, Indiana University, Indianapolis, IN, USA.
¹⁰ Department of Neurodegenerative Disease, Dementia Research Centre, UCL Institute of Neurology, Queen Square, London, UK.
¹¹ Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA; Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.
¹² German Center for Neurodegenerative Diseases (DZNE), München, Germany; Department of Neurology, Ludwig-Maximilians University Munich, Munich, Germany.
¹³ Department of Neurology, The Warren Alpert Medical School of Brown University, Providence, RI, USA.
¹⁴ Division of Biostatistics, The Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St Louis, MO, USA.
¹⁵ Department of Neurology, Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO, USA.
¹⁶ The Florey Institute, The University of Melbourne, Parkville, Victoria, Australia.
¹⁷ Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Abstract

Introduction: Little is known about effects of physical activity (PA) in genetically driven early-onset autosomal dominant Alzheimer's disease (AD).

Methods: A total of 372 individuals participating at the Dominantly Inherited Alzheimer Network study were examined to evaluate the cross-sectional relationship of PA with cognitive performance, functional status, cognitive decline, and AD biomarkers in cerebrospinal fluid. Mutation carriers were categorized as high or low exercisers according to WHO recommendations.

Results: Mutation carriers with high PA showed significantly better cognitive and functional performance and significantly less AD-like pathology in cerebrospinal fluid than individuals with low PA. Mutation carriers with high PA scored 3.4 points better on Mini Mental State Examination at expected symptom onset and fulfilled the diagnosis of very mild dementia 15.1 years later compared with low exercisers.

Discussion: These results support a beneficial effect of PA on cognition and AD pathology even in individuals with genetically driven autosomal dominant AD.

Keywords: Cerebrospinal fluid biomarkers; Cognitive function; Dominantly inherited Alzheimer's disease; Functional status; Mutation carrier; Physical activity.

Publication types

Observational Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Age of Onset
Alzheimer Disease / genetics
Alzheimer Disease / pathology
Alzheimer Disease / physiopathology*
Alzheimer Disease / psychology*
Biomarkers / cerebrospinal fluid
Cognition*
Cross-Sectional Studies
Exercise* / psychology
Female
Heterozygote
Humans
Longitudinal Studies
Male
Mutation

Substances

Biomarkers

Abstract

Publication types

MeSH terms

Substances

Grants and funding