Elevated thyroid hormone associated with dementia in the elderly

Over 2,500 adults aged 70-80 without baseline dementia were followed for 9 years. Patients with subclinical hyperthyroidism and very low TSH, as defined by TSH < 0.10, were found to be at high risk of cognitive decline. On the contrary, subclinical hypothyroidism and subclinical hyperthyroid with TSH 0.1-0.5 were not associated with an increased incidence of dementia. 

Although findings are associative, and not causative, it would still be reasonable to avoid "advanced" subclinical hyperthyroidism in adults >70 years of age. Low dose methimazole could be useful in these individuals assuming absence of medication adverse effects. 

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Objective: Data on the association between subclinical thyroid dysfunction and dementia are limited and conflicting. We aimed to determine whether subclinical thyroid dysfunction was associated with dementia and cognitive decline.

Design: Population-based prospective cohort study.

Patients: Adults aged 70-79 years with measured thyroid function, but no dementia at baseline, and Modified Mini-Mental State (3MS) at baseline and follow-up.

Measurements: Primary outcome was incident-adjudicated dementia, based on 3MS, hospital records and dementia drugs. Secondary outcome was change in 3MS. Models were adjusted for age, sex, race, education and baseline 3MS, and then further for cardiovascular risk factors.

Results: 

Among 2558 adults, 85% were euthyroid (TSH 0.45-4.49mIU/L), 2% had subclinical hyperthyroidism with mildly decreased TSH (TSH 0.1-0.44 mIU/L), 1% subclinical hyperthyroidism with suppressed TSH (TSH < 0.10 mIU/L with normal free thyroxine [FT4]) and 12% subclinical hypothyroidism (TSH 4.50-19.99 mIU/L with normal FT4).

Over 9 years, 22% developed dementia.

Compared to euthyroidism, risk of dementia was higher in participants with subclinical hyperthyroidism with suppressed TSH (HR 2.38, p<0.05).

We found no significant association in those with mildly decreased TSH (HR 0.79, p>0.05) or with subclinical hypothyroidism (HR 0.91, p>0.05).

Participants with subclinical hyperthyroidism with suppressed TSH had a larger decline in 3MS (-3.89, p>0.05).

Conclusions: 

Among older adults, subclinical hyperthyroidism with a TSH < 0.10 mIU/L was associated with a higher risk of dementia and a larger cognitive decline.

While subclinical hyperthyroidism with mildly decreased TSH or subclinical hypothyroidism were not.