ApoE4 Genotype and Dementia: A Biomarker for Personalized Lifestyle Medicine?

Healthy brain aging could be achieved by identifying genetic risk and initiating a personalized lifestyle medicine approach, in fact this may be the best option for mitigating cognitive decline and Alzheimer’s disease.

Age related cognitive decline and Alzheimer’s disease (AD) are amongst the most feared and burdensome chronic illnesses. Cognitive dysfunction however is not an inevitable consequence of aging; for example about 20% of centenarians have no evidence of cognitive decline or neurodegenerative disease. Healthy cognitive ageing and the maintenance of social connectedness, a sense of purpose, and the ability to function independently into old age is a realistic possibility.[1]

Despite considerable research into the neurobiology of AD little advance has been made in mitigating the disease. However, the established interplay between an individual’s genetic predisposition and modifiable environmental risk factors offers an avenue for prevention, and perhaps treatment, with personalized lifestyle medicine.

The apolipoprotein E ε4 allele (ApoE4) is an established genetic modifier and biomarker of AD, which may be useful for defining risk in presymptomatic individuals. Importantly ApoE4 is known to significantly influence the potency of modifiable environmental risk factors.[2] The influence of physical inactivity, dietary fat intake, alcohol, smoking and psychological stress on AD risk are all magnified in carriers of the ApoE4 allele. [3] [4]

ApoE4 genotype is also associated with low brain energy reserve.[5]  Impaired brain energy metabolism is know to affect cognitive function and may contribute to cognitive decline by compromising brain plasticity.[6] This raises the possibility of optimizing the intake of dietary factors known to enhance brain energy metabolism and improve cognitive function in APOE4 carriers (e.g. micronutrients, phytochemicals, carnitine and creatine).[7]

It has been proposed that early risk assessment, early intervention, continuous management and lifestyle change represent the future of effective AD care.[8] The application of a personalized lifestyle medicine approach that centers on addressing environmental risk factors and optimizing neurological function in genetically susceptible individuals may provide a framework for healthy brain ageing.



[1] Desai AK, Grossberg GT, Chibnall JT. Healthy brain aging: a road map. Clin Geriatr Med. 2010 Feb;26(1):1-16. doi: 10.1016/j.cger.2009.12.002. Review. PubMed PMID: 20176289.
[2] Schipper HM. Apolipoprotein E: implications for AD neurobiology, epidemiology  and risk assessment. Neurobiol Aging. 2011 May;32(5):778-90.
[3] Kivipelto M, Rovio S, Ngandu T, et al. Apolipoprotein E epsilon4 magnifies lifestyle risks for dementia: a population-based study. J Cell Mol Med. 2008 Dec;12(6B):2762-71.
[4] Comijs HC, van den Kommer TN, Minnaar RW, et al. Accumulated and differential effects of life events on cognitive decline in older persons: depending on depression, baseline cognition, or ApoE epsilon4 status? J Gerontol  B Psychol Sci Soc Sci. 2011 Jul;66 Suppl 1:i111-20.
[5] Laakso MP, Hiltunen Y, Könönen M, et al. Decreased brain creatine levels in elderly apolipoprotein E epsilon 4 carriers. J Neural Transm. 2003 Mar;110(3):267-75.
[6] Gibson GE, Starkov A, Blass JP, et al. Cause and consequence: mitochondrial dysfunction initiates and propagates neuronal dysfunction, neuronal death and behavioral abnormalities in age-associated neurodegenerative diseases.  Biochim Biophys Acta. 2010 Jan;1802(1):122-34.
[7] Brown BI. Nutritional Brain Energy Enhancement for Reducing Mental Fatigue and Improving Mood and Cognition. JOM, 2012; 27(4): 177-186.
[8] de la Torre JC. A turning point for Alzheimer's disease? Biofactors. 2012 Mar-Apr;38(2):78-83.



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