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Multiple Biological Pathways Link Cognitive Lifestyle to Protection from Dementia

  • Michael J. Valenzuela
    Correspondence
    Address correspondence to Michael J. Valenzuela, BSc Hons, MBBS Hons, Ph.D., University of New South Wales, Regenerative Neuroscience Group, School of Psychiatry, Sydney, Australia
    Affiliations
    Regenerative Neuroscience Group, University of New South Wales, Sydney, Australia

    School of Psychiatry, University of New South Wales, Sydney, Australia

    Brain and Ageing Research Program, University of New South Wales, Sydney, Australia
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  • Fiona E. Matthews
    Affiliations
    Medical Research Council Biostatistics Unit, Institute of Public Health, School of Clinical Medicine, University of Cambridge, Cambridge
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  • Carol Brayne
    Affiliations
    Department of Public Health and Primary Care, Institute of Public Health, School of Clinical Medicine, University of Cambridge, Cambridge
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  • Paul Ince
    Affiliations
    Department of Neuroscience, University of Sheffield, Sheffield, United Kingdom
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  • Glenda Halliday
    Affiliations
    Faculty of Medicine, University of New South Wales, Sydney, Australia

    Neuroscience Research Australia, Sydney Medical School, The University of Sydney, Sydney, Australia
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  • Jillian J. Kril
    Affiliations
    Discipline of Pathology, Sydney Medical School, The University of Sydney, Sydney, Australia

    Discipline of Medicine, Sydney Medical School, The University of Sydney, Sydney, Australia
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  • Marshall A. Dalton
    Affiliations
    Regenerative Neuroscience Group, University of New South Wales, Sydney, Australia

    Neuroscience Research Australia, Sydney Medical School, The University of Sydney, Sydney, Australia

    Discipline of Pathology, Sydney Medical School, The University of Sydney, Sydney, Australia
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  • Kathryn Richardson
    Affiliations
    Department of Public Health and Primary Care, Institute of Public Health, School of Clinical Medicine, University of Cambridge, Cambridge
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  • Gill Forster
    Affiliations
    Department of Neuroscience, University of Sheffield, Sheffield, United Kingdom
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  • Perminder S. Sachdev
    Affiliations
    School of Psychiatry, University of New South Wales, Sydney, Australia

    Brain and Ageing Research Program, University of New South Wales, Sydney, Australia

    Neuropsychiatric Institute, Prince of Wales Hospital, Sydney, Australia
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  • Medical Research Council Cognitive Function and Ageing Study
Published:November 07, 2011DOI:https://doi.org/10.1016/j.biopsych.2011.07.036

      Background

      An active cognitive lifestyle is linked to diminished dementia risk, but the underlying mechanisms are poorly understood. Potential mechanisms include disease modification, neuroprotection, and compensation. Prospective, population-based brain series provide the rare opportunity to test the plausibility of these mechanisms in humans.

      Methods

      Participants came from the United Kingdom Medical Research Council Cognitive Function and Ageing Study, comprising 13,004 individuals aged over 65 years and followed for 14 years. In study 1, a Cognitive Lifestyle Score (CLS) was computed on all Cognitive Function and Ageing Study subjects to define low, middle, and high groups. By August 2004, 329 individuals with CLS data had come to autopsy and underwent Consortium to Establish a Registry of Alzheimer's Disease assessment. Study 2 involved more detailed quantitative histology in the hippocampus and Brodmann area 9 in 72 clinically matched individuals with high and low CLS.

      Results

      CLS groups did not differ on several Alzheimer disease neuropathologic measures; however, high CLS men had less cerebrovascular disease after accounting for vascular risk factors, and women had greater brain weight. No group differences were evident in hippocampal neuronal density. In Brodmann area 9, cognitively active individuals had significantly greater neuronal density, as well as correlated increases in cortical thickness.

      Conclusions

      An active cognitive lifestyle was associated with protection from cerebrovascular disease in men, but there was no evidence for Alzheimer disease modification or hippocampal neuroprotection. Men and women both exhibited neurotrophic changes in the prefrontal lobe linked to cognitive lifestyle, consistent with a compensatory process. Lifespan complex cognitive activity may therefore protect against dementia through multiple biological pathways.

      Key Words

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      Linked Article

      • Is the Idle Mind a Devil's Workshop?
        Biological PsychiatryVol. 71Issue 9
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          The use-it-or-lose-it theory posits that the brain can be influenced by how we use it, much like a muscle, and that an enriched environment along with a cognitively active lifestyle can prevent or postpone dementia. The popularity of this theory has been fueled by the rapid growth of aging baby boomers, the lack of pharmacologic therapies for preventing dementia, and companies seeking to cater to this need. Approximately 80% of the 38,000 adults older than 50 years surveyed in the 2010 American Association of Retired Persons Member Opinion Survey indicated staying mentally sharp as their top-ranked interest and concern, above other important concerns such as social security and Medicare (1).
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