Graves disease is associated with increased risk of clinical Alzheimer's disease: evidence from the Medicare system

Abstract

Background: Identification of modifiable risk factors for Alzheimer's Disease (AD) onset is an important aspect of controlling the burden imposed by this disease on an increasing number of older U.S. adults. Graves disease (GD), the most common cause of hyperthyroidism in the U.S., has been hypothesized to be associated with increased AD risk, but there is no consensus. In this study, we explore the link between GD and risk of clinical AD.

Methods: Cox and Fine-Grey models were applied to a retrospective propensity-score-matched cohort of 19,798 individuals with GD drawn from a nationally representative 5% sample of U.S. Medicare beneficiaries age 65 + over the 1991-2020 period.

Results: Results showed that the presence of GD was associated with a higher risk of AD (Hazard Ratio [HR]:1.19; 95% Confidence Interval [CI]:1.13-1.26). Competing risk estimates were consistent with these findings (HR:1.14; CI:1.08-1.20) with the magnitude of associated risk varying across subgroups: Male (HR:1.25; CI:1.07-1.47), Female (HR:1.09; CI:1.02-1.16), White (HR:1.11; CI:1.03-1.19), and Black (HR:1.23; CI:1.02-1.49).

Conclusions: Our results indicate a robust and consistent association between a diagnosis of GD and a subsequent diagnosis of AD in later stages of life. The precise biological pathways that could potentially connect these two conditions remain unclear as is the role of treatment in this relationship. Replications of these findings on datasets with both biomarkers and laboratory test results, especially in underrepresented groups is vital.

Keywords: Alzheimer’s disease; Dementia; Graves disease; Hyperthyroidism; Medicare.

Fig. 1

Trends in graves disease prevalence. Trend in the prevalence of individuals ever to be diagnosed with Graves Disease (per 100,000). Full sample, Graves Disease an absorbing state (A black solid line); Full sample, Graves Disease in remission after 5 years (A black dashed line); Males B black dotted line), Females (B black dot-dash line), White (C black solid line), Black (C blue solid line), Hispanic (C red solid line), other (C green solid line)

Fig. 2

Trends in graves disease incidence. Trend in the incidence of Graves Disease (per 100,000).  Full sample (A black solid line) Males (B black dotted line), Females (B black dash line), White (C black solid line), Black (C blue solid line), Hispanic (C red solid line), other (C green solid line)