"Levels of bioavailable testosterone were not associated with risk of cognitive decline and incident dementia," they report. "In contrast, higher levels of bioavailable estradiol were associated with an increased risk for cognitive decline and Alzheimer's disease." For each standard deviation increase in estradiol level, the risk for the disease went up by 25 percent. Furthermore, compared with the lowest tertile of estradiol, men in the middle and highest tertile had .24 and .28 points lower CASI scores, respectively, for each year increase in age.
The researchers hypothesize that the estradiol association could be explained by increased aromatase activity in the brain which may be associated with a neurodegenerative process. It is then possible that the high levels of estradiol are a consequence or early marker of Alzheimer's disease rather than a cause.
Some caution is needed when interpreting the results, as, due to death or refusal, some men could not be given a diagnosis of dementia or follow-up cognitive testing.
In conclusion, the authors report, "our findings of an increased risk of cognitive decline and Alzheimer's disease associated with higher estradiol are similar to recent findings in postmenopausal women. Further studies are needed to examine whether there are mechanisms by which estradiol may increase risk of cognitive decline and dementia."