The Association of Thyroid Function on Cognition and Neuropsychiatric Symptoms in Patients with Cognitive Impairment

This study aims to investigate the association between thyroid function, cognitive status, and neuropsychiatric symptoms (NPSs) in patients with mild cognitive impairment or dementia.

This cross-sectional analysis enrolled 2,289 patients newly diagnosed with mild cognitive impairment or dementia. Based on thyroid-stimulating hormone and free thyroxine levels, patients were classified into euthyroid, hypothyroid, and hyperthyroid groups, with subclinical and overt forms incorporated into their respective categories due to group size distribution. NPSs were assessed using the Neuropsychiatric Inventory. Multivariate logistic regression evaluated associations between thyroid function and NPSs, while linear regression examined relationships with cognitive status.

Significant differences in Clinical Dementia Rating-Sum of Boxes (CDRSOB) and Cognitive Abilities Screening Instrument (CASI) scores were observed across the three thyroid function groups (mean CDRSOB: euthyroid = 4.6, hyperthyroidism = 5.4, hypothyroidism = 5.3, p = 0.013; mean CASI: euthyroid = 51.6, hyperthyroidism = 47.2, hypothyroidism = 49.0, p = 0.028). Patients in the hyperthyroid group demonstrated higher odds of experiencing delusion (odds ratio (OR) = 1.61, 95% confidence interval (CI) = 1.12-2.31, p = 0.009), agitation (OR = 1.47, 95% CI = 1.00-2.13, p = 0.048), and moderate to severe hallucination (OR = 1.76, 95% CI = 1.01-2.92, p = 0.037). After adjusting for age, education, and dementia subtypes, patients in the hyperthyroid group had significantly worse CDRSOB scores than those in the euthyroid group (β = 0.66, 95% CI = 0.03-1.3, p = 0.040).

This study provides the first structured evaluation of behavioral and psychological symptoms of dementia across thyroid function states in patients with cognitive impairment. Hyperthyroidism was associated with worse global function and a higher prevalence of delusions, agitation, and moderate-to-severe hallucinations. These findings highlight an association between thyroid dysfunction and BPSD (behavioral and psychological symptoms of dementia) in cognitively impaired populations and underscore the importance of careful clinical evaluation of thyroid status.