Treated hypothyroidism is associated with cerebrovascular disease but not Alzheimer's disease pathology in older adults

Thyroid hormone disease is common among older adults and is associated with cognitive impairment. However, pathologic correlates are not well understood. We studied pathologic and clinical factors associated with hypothyroidism, the most common manifestation of thyroid disease, in research subjects seen annually for clinical evaluations at U.S. Alzheimer's Disease Centers. Thyroid disease and treatment status were assessed during clinician interviews. Among autopsied subjects, there were 555 participants with treated hypothyroidism and 2146 without known thyroid disease; hypothyroidism was associated with severe atherosclerosis (odds ratio: 1.35; 95% confidence interval: 1.02, 1.79) but not Alzheimer's disease pathologies (amyloid plaques or neurofibrillary tangles). Among participants who did not undergo autopsy (4598 with treated hypothyroidism and 20,945 without known thyroid hormone disease), hypercholesterolemia and cerebrovascular disease (stroke and/or transient ischemic attack) were associated with hypothyroidism, complementing findings in the smaller autopsy sample. This is the first large-scale evaluation of neuropathologic concomitants of hypothyroidism in aged individuals. Clinical hypothyroidism was prevalent (>20% of individuals studied) and was associated with cerebrovascular disease but not Alzheimer's disease–type neuropathology.