I found 8 studies for review; unfortunately only 2 reviewed APOE4 status. The 6 that did not review APOE4 status all stated that physical activity was beneficial to prevent AD. Most of these involved person 65 or older and were followed for about 5 years.
The Kivipeto study "APOE4 magnifies lifestyle risk for dementia", (28) found odds ratio 2.4 for dementia in APOE4 carriers for sedentary vs active life style. Non-E4 carriers had a 1.7 odds ratio for sedentary vs active lifestyle. Persons were followed for 20 years from age 50 to age 70.
The following study found no benefit for APOE4 carriers. In contrast, non-E4 carriers had a reduction in risk of dementia associated with physical activiity. "Physical activity, APOE gene type, and dementia risk: finding from Cardiovascular Health Cognition Study", Podewils, 2005. (87) This was a U.S. study which followed 3375 men and women aged 65 or older, free of dementia at baseline for mean of 5.4 years. The most active quartile had reduced odds ratio of 0.51. Reduced odds ratio: "ABSENT IN (E4) CARRIERS".
The Podewils study should be viewed in combination with Qiu angiotensin II study (83)) above which showed in 75 years olds and above, APOE4 carriers had no benefit from treatment of hypertension in contrast to E4 negative group which has reduction in risk with treatment of hypertension.
The Podewils exercise study, the Qiu hypertension study, the Kivipelto lifestyle study all show AD in APOE4 carriers is a different disease and all intervention studies must be specific for APOE4 status.
Note that Kivipelto study followed middle-age persons for 20 years; but the Podewils study followed old-age persons, 65 and older. The two studies show that in APOE4 carriers, physical activity is of very marked value in middle age group to prevent AD in future in older age group; but of minimal value to prevent AD when done in older age group.
Note that physical activity can still be of marked value to prevent cardiovascular disease and diabetes in APOE4 carriers in 65 and above age group; however, physical activity may not be of much value to lower risk of AD in older age group.
The explanation may be that preventive measures are most effective before damage done.
Since APOE4 carriers may be developing damage decades before non-E4 carriers, they need to take precautions before the damage is done.
The minimum recommended level of physical activity is generally given as 30 minutes of moderate activity, 5 times a week.
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