Brain-derived neurotropic factor (BDNF) is an abundant and multi-function neurotrophin in the brain. It is released following neuronal activity and is believed to be particularly important in strengthening neural networks. A common variation in the BDNF gene, a valine to methionine substitution at codon 66 (Val66Met), has been linked to differential expression of BDNF associated with experience-dependent plasticity. The Met allele has been associated with reduced production of BDNF following neuronal stimulation, which suggests a potential role of this variation with respect to how the nervous system may respond to challenges, such as brain ageing and related neurodegenerative conditions (e.g., dementia and Alzheimer's disease). The current review examines the potential of the BDNF Val66Met variation to modulate an individual's susceptibility and trajectory through cognitive changes associated with ageing and dementia. On balance, research to date indicates that the BDNF Met allele at this codon is potentially associated with a detrimental influence on the level of cognitive functioning in older adults and may also impart increased risk of progression to dementia. Furthermore, recent studies also show that this genetic variation may modulate an individual's response to interventions targeted at building cognitive resilience to conditions that cause dementia.

Centre for Health Care of the Elderly QEII Health Sciences Centre Nova Scotia Health Authority Halifax NS B3H 2E1 Canada

Division of Geriatric Medicine Department of Medicine Dalhousie University Halifax NS B3H 2E1 Canada

International Clinical Research Center St Anne's University Hospital Brno 65691 Brno Czech Republic

Memory Clinic Department of Neurology 2nd Faculty of Medicine Charles University and Motol University Hospital 15006 Prague Czech Republic

Wicking Dementia Research and Education Centre College of Health and Medicine University of Tasmania Hobart 7001 Tasmania Australia

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Mild behavioral impairment in early Alzheimer's disease and its association with APOE and BDNF risk genetic polymorphisms

The Combined Effect of APOE and BDNF Val66Met Polymorphisms on Spatial Navigation in Older Adults