New research for those with high genetic risk for Alzheimer’s

If you have a high genetic risk for developing Alzheimer’s Disease (AD), research presented at the Alzheimer’s Association Annual Conference in July gives some hope. In a University of Exeter study of almost 200,000 people, those with high genetic risk and a healthy lifestyle were less likely to develop dementia during the follow-up period than those with high risk/unfavorable lifestyle.  This is the first time a study showed a positive effect for lifestyle intervention on those with increased risk.  The people were followed for eight years, which is a short time for a dementia study.

Among participants with high genetic risk, 1.13% of those with a favorable lifestyle developed dementia compared to 1.78% with an unfavorable lifestyle.

Your genes represent 60-80% of the risk for AD, according to current research.  While the

APoE4 gene is the strongest one found so far, other genes increase the risk when combined with the APoE4 (polygenic).  This study used the combined polygenic risk score to evaluate AD risk.  Previous lifestyle intervention studies saw a positive effect for everyone but those with the APoE4 gene.

Lifestyle was scored by assessing smoking status, physical activity, diet, and alcohol consumption.  Study authors used the American Heart Association recommendations of 150 minutes of moderate activity per week or 75 minutes of vigorous activity to gauge physical activity.  A healthy diet meant following recommendations for cardiac health.  Alcohol consumption studies show a U-curve where moderate drinkers had a lower AD risk. The standard for moderate consumption is 14 gm/day for women and 28 gm/day for men, which is 5 oz of wine or 12 oz of beer for women.  The analysis used this standard to score alcohol.

The hazard ratio (HR) is an easy to understand number that compares low risk against other categories.  A person with low genetic risk would be a “1” as a starting point to compare risk.  In this study, intermediate-risk has an HR of 1.37, and high genetic risk for Alzheimer’s is 1.91.

People rarely have just one thing wrong with their health.  Comorbidity (simultaneous chronic diseases or conditions) makes AD research even more difficult.  The Exeter study showed stroke history combined with high genetic risk and unfavorable lifestyle resulted in an HR of 2.74.



The bottom line for this study is that “a favorable lifestyle was associated with a lower risk of dementia regardless of genetic risk.”


It can be very hard to keep up a healthy lifestyle for a long-term benefit.  It’s well-documented that conscientious people are healthier and live longer.  Geriatrician Michael McCloud, MD, told us at the UC Davis Mini-Medical school lecture series that he believes Alzheimer’s might be the result of a lifetime’s insults to the brain.  Current recommendations for heart disease include keeping your blood pressure below 120/80.  For people over 50, this may require real effort.  Focusing on cardiac health may be enough to take advantage of the healthy lifestyle protective factor for dementia.


James Clear writes about sustained success in Atomic Habits:

“Changing your beliefs isn’t nearly as hard as you might think.  There are two steps.

  1. Decide the type of person you want to be.

  2. Prove it to yourself with small wins.

You can’t rely on being motivated.  You have to become the type of person you want to be, and that starts with proving your new identity to yourself.”


So if you want to be a conscientious person who will likely live a long, productive, healthy, and independent life, you have to choose that identity rather than hope it will turn out that way.  Until there’s a cure for Alzheimer’s, this is the only thing we can do.

Lourida I, Hannon E, Littlejohns TJ, et al. Association of Lifestyle and Genetic Risk With Incidence of Dementia. JAMA. Published online July 14, 2019322(5):430–437. doi:10.1001/jama.2019.9879

#AlzheimersDisease #APoE4 #healthyliving

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