Multiple Biological Pathways Link Cognitive Lifestyle to Protection from Dementia

Valenzuela, Michael J.; Matthews, Fiona E.; Brayne, Carol; Ince, Paul; Halliday, Glenda; Kril, Jillian J.; Dalton, Marshall A.; Richardson, Kathryn; Forster, Gill; Sachdev, Perminder S.; Medical Research Council Cognitive Function and Ageing Study,

doi:10.1016/j.biopsych.2011.07.036

« Previous Next »Biological Psychiatry
Volume 71, Issue 9 , Pages 783-791, 1 May 2012

Multiple Biological Pathways Link Cognitive Lifestyle to Protection from Dementia

Michael J. Valenzuela
- 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
- 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
Fiona E. Matthews
- Medical Research Council Biostatistics Unit, Institute of Public Health, School of Clinical Medicine, University of Cambridge, Cambridge
Carol Brayne
- Department of Public Health and Primary Care, Institute of Public Health, School of Clinical Medicine, University of Cambridge, Cambridge
Paul Ince
- Department of Neuroscience, University of Sheffield, Sheffield, United Kingdom
Glenda Halliday
- Faculty of Medicine, University of New South Wales, Sydney, Australia
- Neuroscience Research Australia, Sydney Medical School, The University of Sydney, Sydney, Australia
Jillian J. Kril
- Discipline of Pathology, Sydney Medical School, The University of Sydney, Sydney, Australia
- Discipline of Medicine, Sydney Medical School, The University of Sydney, Sydney, Australia
Marshall A. Dalton
- 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
Kathryn Richardson
- Department of Public Health and Primary Care, Institute of Public Health, School of Clinical Medicine, University of Cambridge, Cambridge
Gill Forster
- Department of Neuroscience, University of Sheffield, Sheffield, United Kingdom
Perminder S. Sachdev
- 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
Medical Research Council Cognitive Function and Ageing Study

Received 29 April 2011; received in revised form 13 July 2011; accepted 26 July 2011. published online 07 November 2011.

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: Cortical thickness , dementia , mental activity , neuronal density , neuropathology , protective factors