Thursday, February 1, 2018

Genetic Predisposition to Alzheimer’s Does Not Prevent Lifestyle Intervention from Helping


A large, ongoing study of a multipart lifestyle intervention (Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability) has been investigating the ability of this type of treatment to prevent cognitive decline in older subjects.  One of the latest analyses in this study sought to determine if the most common genetic variant that increases Alzheimer’s risk, the apoE4 gene variation, would prevent these individuals from benefiting from this intervention as persons without the gene variant.

Subjects between the ages of 60 and 77 were blindly randomized to the intensive management group which included diet, exercise, cognitive training, and vascular risk management, while the control subjects received only general health advice.  Equal numbers of participants in each group carried the high risk (3-10 times) apoE4 gene or the normal risk apoE3 gene.

Cognitive function was measured before the study with a comprehensive neuropsychological test battery and after 6 years.  Those participating in the intensive management group had significantly better cognitive scores at the end of the 6 years, and the benefit was the same in both the normal or high genetic risk subjects.  The two important conclusions are that a comprehensive lifestyle management program does prevent cognitive decline and that this prevention occurs both in those with and without the apoE mediated risk. 

These results are reassuring as approximately 1 in 6 adults have the higher risk apoE4 gene.  While this genetic variant increases their risk to the development of the disease, it does not prevent the benefits of a comprehensive lifestyle management program from helping.  The increased risk associated with the apoE4 gene appears to require those with it to be more meticulous about their lifestyle both to prevent the disease onset as well as to manage it once cognitive decline appears.

The above statement does not give a free ride about being less concerned about lifestyle management to those with the “normal risk” apoE3 gene.  The normal risk for Alzheimer’s is still 1 out of 6 by age 65-70, and 1 out of 3 by age 80.  Dale Bredesen, MD the innovator of the successful lifestyle program called ReCODE, explains the relationship between lifestyle and Alzheimer’s risk best based on extensive research.  He comments that Alzheimer’s appears to not be just a brain disease but rather a brain manifestation of systemic metabolic disease.  An example of this relationship is the 2-3 times greater risk of Alzheimer’s in those who develop type two diabetes which is highly related to lifestyle.

ApoE4 remains a risk factor for the development of Alzheimer’s disease.  While it increases this risk, it fortunately does not compromise the ability of a comprehensive lifestyle management program to help the disease once signs of it are present.  Importantly, the apoE4 genotype serves as a warning of the disease risk and the important preventative role of a comprehensive lifestyle program before the disease manifests.  The best treatment is not to develop the disease in the first place.

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