Early-Onset Ocular Motor Cranial Neuropathy Is a Strong Predictor of Dementia: A Nationwide, Population-Based Cohort Study

Abstract

PurposeTo assess the risk of dementia in individuals with newly diagnosed ocular motor cranial neuropathy (OMCN). DesignA nationwide, population-based cohort study using authenticated data from the Korean National Health Insurance Service (KNHIS). SubjectsThis study included 60,781 OMCN patients diagnosed between 2010 and 2017 and followed through 2018, with an average follow-up of 3.37 (SD, 2.21) years with a one-year lag. After excluding patients with disease related to oculomotor dysfunction preceding the OMCN diagnosis (e.g., dysthyroid exophthalmos, thyrotoxicosis, or myasthenia gravis), a total of 52,076 OMCN cases were established. Of these, 23,642 patients who had participated in the National Health Screening Program (NHSP) within two years before their OMCN diagnosis were included. After applying the exclusion criteria (e.g., age < 40 years, previous dementia, and patients with missing data), the final cohort consisted of 19,243 patients and 96,215 age- and sex-matched controls without OMCN. MethodsWe identified newly diagnosed OMCN in the KNHIS database and collected participant characteristics from the health checkup records of the NHSP. The study endpoint was determined by the first claim with a dementia diagnostic code and anti-dementia medications. OMCN’s association with dementia risk was examined using Cox proportional hazards regression analysis, adjusting for age, sex, behavioral factors, and systemic comorbidities. Main Outcome MeasuresThe main outcome measures were hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause dementia (ACD), Alzheimer’s disease (AD), and vascular dementia (VaD) development in OMCN patients relative to those without OMCN. ResultsNewly diagnosed OMCN patients demonstrated higher metabolic comorbidities than non-OMCN individuals. New OMCN was associated with an elevated risk of ACD (HR = 1.203, 95% CI: 1.113 − 1.300), AD (HR = 1.137, 95% CI: 1.041 − 1.243), and VaD (HR = 1.583, 95% CI: 1.286 − 1.948), independent of potential confounding factors. The younger age groups exhibited a stronger association between OMCN and ACD (HR = 8.690 [< 50 years] versus 1.192 [≥ 50 years], P = 0.0004; HR = 2.517 [< 65 years] versus 1.099 [≥ 65 years], P < 0.0001). ConclusionsThis study represents the first nationwide population-based epidemiological study assessing the association between OMCN and dementia risk. Our results demonstrated a robust relationship between OMCN and the risk of developing dementia, particularly in the younger population.