Genetic evidence suggests a causal relationship linking thyroid function to prospective memory and dementia and Parkinson's disease

Abstract

Epidemiological studies suggest a link between thyroid function and prospective memory (PM), but more evidence is required. We used a two-sample Mendelian randomization (MR) study to explore this. Utilizing data from genome-wide association studies, the exposures included thyroid cancer (TC), thyroid-stimulating hormone (TSH), hypothyroidism, hyperthyroidism (HT), and radiation (RAD), while the outcome variables consisted of PM, Parkinson's disease (PD) and four dementia subtypes: Alzheimer's disease (AD), Lewy body dementia (DLB), frontotemporal dementia (FTD), and vascular dementia (VD). The inverse-variance weighted (IVW) method was the primary MR analysis. Heterogeneity testing and sensitivity analyses affirmed the robustness of the MR results. TSH was causally linked to PD [OR = 0.811, 95% CI = 0.692-0.951, p = 0.010]. Hypothyroidism was causally associated with AD and DLB [AD OR = 0.954, 95% CI = 0.916-0.993, p = 0.022; DLB OR = 0.845, 95% CI = 0.745-0.959, p = 0.009]. There might be a causal relationship between hypothyroidism and both PD and PM, while HT might influence PM. TC and RAD showed no causal relationship with PM, PD and dementia. TSH serves as a protective factor against PD, while hypothyroidism is a protective factor against AD and DLB. Hypothyroidism may pose a risk for PM deficits and PD, whereas HT may be a risk factor for PM. Additionally, TC and RAD does not appear to cause damage to PM, PD and increase dementia risk.

Keywords: Dementia; Prospective memory; Radiation; Thyroid function; Two-sample Mendelian randomization.

Fig. 1

Flowchart of the mendelian randomization study.