. Midlife cardiovascular fitness and dementia: A 44-year longitudinal population study in women. Neurology. 2018 Apr 10;90(15):e1298-e1305. Epub 2018 Mar 14 PubMed.


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  1. While this study is interesting since it seeks to correlate midlife (rather than elderly) fitness with AD risk, it has two major limitations that caution against reading too much into these findings. In addition to the small sample size mentioned above by Drs. Vemuri and Kivipelto, the authors did not report any APOE genotype information for the sample, which consisted of 191 women divided into low (n=59), medium (n=92), and high (n=40) levels of midlife fitness. It is easily possible with a sample of this size that the high fitness group randomly had fewer carriers of the APOE E4 allele than would be expected from population genetics (or, the other groups had more carriers than expected).

    The authors mention in their discussion that without this genetic information they "cannot draw any conclusions about the impact of APOE E4 on the relation between fitness and dementia." But my feeling is that without this genetic information, a study of this size should not draw any conclusions about the relation between fitness and dementia, period. Given the ~300 percent increase in AD risk conferred by each copy of the APOE E4 allele that one might carry, correcting for this genetic factor is an essential component for any epidemiological study of AD risk, particularly when the sample is small.

    Despite these limitations, the study does provide some added motivation for me to increase the frequency of my visits to our company's physical fitness facility!

    View all comments by DAVID HANSEN
  2. I absolutely agree that favourable genes (e.g not APOE4) could explain both the high cardiovascular fitness (healthy heart) and the decreased dementia risk (healthy brain).

    View all comments by Helena Hörder

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  1. 44-Year Study Ties Midlife Fitness to Lower Dementia Risk