Mechanism Unclear

This study, he said, was an effort to shed more light on this connection. "We thought maybe we'd find a
relationship one way or the other, but it was interesting to find that both low and high levels were
associated" with Alzheimer's disease, Dr. Tan told Medscape Neurology & Neurosurgery.
Finding that this association existed at both ends of the spectrum was enlightening, he added. "The fact
that the brain tries to maintain thyroid levels at a relatively narrow range may suggest that for it to function
optimally, it has to be maintained within this range and going below or above that is not a good thing."
It's not clear, though, how thyroid hormone levels outside this optimal range might trigger Alzheimer's
disease. High levels of the hormone could increase oxidative stress, and low levels might affect
brain tissue and circulating levels of beta amyloid peptide, the study authors surmise.
Also, it is possible that changes in the brain may affect the amount of thyrotropin in the
bloodstream. The study authors speculate that these brain changes could alter the body's ability to
respond to this hormone.
It is also unclear why thyroid hormone levels affect Alzheimer's disease risk in women but not in men. "I
don't think anyone has provided an answer to that yet," said Dr. Tan. "There's something about either the
brain of women or the hormonal milieu of women that makes them more prone to this effect."
"What we do know is that, for some reason, thyroid problems for example, hypothyroidism, which is
related to depression are more common in women," he said.
Another consideration is that thyroid problems simply become more common with age as does dementia.
"One has to question whether these things are there just because one is getting old, or if there is some
connection between the two conditions," said Dr. Tan.
Today, thyroid dysfunction is underdiagnosed in clinical practice, and some clinicians are advocating for
more intense screening for thyroid problems, especially among older patients, said Dr. Tan. Some
organizations have already formally questioned whether the currently accepted standard cutoff point should
be narrowed for more optimal outcomes, he said. For example, the American Association of Clinical
Endocrinologists has proposed modifying target thyrotropin levels from the widely accepted 0.5 to 5.0
mIU/L to the narrower range of 0.3 to 3.04 mIU/L.
Would maintaining a narrower range of thyroid hormone levels prevent Alzheimer's disease? This question
will take some time to answer. Although thyroid dysfunction is linked to dementia, depression, and other
cognitive problems, "whether maintaining hormone levels within limits will actually prevent dementia I think
might be a big jump," said Dr. Tan. "That will have to be proven in clinical trials."
This study was supported by the Framingham Heart Study of the National Heart, Lung, and Blood Institute;
the National Institutes of Health; the Precursors of Stroke from the National Institute of Neurological

Disorders and Stroke; and the Magnetic Resonance Imaging, Genetic and Cognitive Precursors of
Alzheimer's Disease and Dementia and the Epidemiology of Dementia in the Framingham Study from the
National Institute on Aging. The study authors have disclosed no relevant financial relationships.