The thyroid gland can be a capricious organ, spilling out too much or too little of its vital hormones. This excess or lack can lead to a panoply of debilitating mental conditions. Indeed, physicians will typically check thyroid hormone levels when patients come in complaining about memory loss or depression. It now appears that they may have another reason to check their female patients’ thyroid function. A new study suggests that women with low or high levels of thyroid--stimulating hormone (TSH) are more likely to develop Alzheimer’s disease than those with normal activity.
Zaldy Tan and his colleagues followed 1,864 people enrolled in the Framingham Study. The subjects’ thyroid function, and specifically their thyroid-stimulating hormone levels, were measured between 1977 and 1979. Tan, an HMS assistant professor of medicine at Beth Israel Deaconess Medical Center, working with colleagues at HMS and Boston University, followed the subjects an average of 12.7 years later and found that women with TSH values in the lowest and highest third (TSH <1.0 mIU/L or >2.1 mIU/L) were twice as likely to develop Alzheimer’s disease as those in the middle third. Men were not at similar risk.
The findings, which appear in the July 28 Archives of Internal Medicine, are notable for several reasons. To begin, doctors have assumed that the effects of low and high TSH levels can be reversed by supplementing or suppressing hormone production. The findings by Tan and colleagues, which corroborate an earlier but smaller study by a Rotterdam group, suggest there may be irreversible consequences.
What is also surprising is that the Alzheimer’s-prone tertiles included subjects with TSH values in the normal range, as judged by traditional standards. “There has been a move to narrow down the range by the American Association of Clinical Endocrinologists,” said Tan.
Perhaps most puzzling is that only women were vulnerable to the effects of aberrant hormone production. “The gender modification effect is the part that is difficult to explain,” said Tan. In fact, women appear to be more vulnerable to other thyroid-associated conditions such as Graves disease. “Nobody even knows exactly why Graves disease and other thyroid dysfunctions are more common in women.”
As for how exactly thyroid dysregulation gives rise to Alzheimer’s disease, Tan and colleagues do identify an intriguing hypothesis. It turns out, thyroid hormone regulates the expression of the amyloid precursor protein (APP) gene, which is known to play a role in Alzheimer’s. According to Tan, too little or too much thyroid hormone could lead to dysregulation of APP and possibly to aberrant production of plaque-causing amyloid protein.
Conflict Disclosure: The authors declare no conflicts of interest.
Funding Sources: The Framingham Heart Study of the National Heart, Lung, and Blood Institute, the National Institutes of Health, the National Institute of Neurological Disorders and Stroke, and the National Institute on Aging
