JAMA / Archives – Women with low or high levels of the hormone thyrotropin , or TSH , which affects thyroid gland function and thyroid hormone levels, appear to have a higher risk of developing Alzheimer’s disease, according to a report in the July 28, 2008 issue of Archives of Internal Medicine .

A clinically detectable over- or under-active thyroid has long been recognized as a potentially reversible cause of cognitive (thinking, learning and memory) impairment. Previous studies have examined whether levels of thyrotropin (TSH), a hormone that is secreted by the pituitary gland and helps regulate thyroid gland function, is associated with cognitive performance in individuals with normal thyroid function. However, results have been inconsistent.

Zaldy S. Tan, M.D., M.P.H., of Hebrew SeniorLife, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, and colleagues measured thyrotropin levels in 1,864 individuals (average age 71) without cognitive problems between 1977 and 1979. Participants were part of the community-based Framingham Study and were assessed for dementia at that time and again every two years.

Over an average of 12.7 years of follow-up, 209 participants developed Alzheimer’s disease. After adjusting for other related factors, the researchers found that women with the lowest (TSH less than 1 milli-international unit per liter) and highest (TSH more than 2.1 milli-international units per liter) thyrotropin levels had more than double the risk of developing Alzheimer’s disease. However, no relationship was observed between thyrotropin levels and Alzheimer’s disease risk in men.

“Whether altered thyrotropin levels occur before or after the onset of Alzheimer’s disease, the neuropathologic mechanism is unclear,” the authors write. Changes in the brain caused by Alzheimer’s disease may cause a reduction in the amount of thyrotropin released or changes in the body’s responsiveness to the hormone. Alternatively, low or high thyrotropin levels could damage neurons or blood vessels, leading to cognitive difficulties.

“In conclusion, low and high thyrotropin levels were associated with an increased risk of incident Alzheimer’s disease in women but not in men,” the authors conclude. “These findings should be considered hypothesis–generating and should be validated in other populations before clinical conclusions are drawn” (Arch Intern Med. 2008;168[14]:1514-1520).