PLOS ONE · 4 authors, 6 centres
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In a large Korean cohort of 650,476 adults with hypertension, age was the strongest predictor of dementia, followed by comorbidity burden and female sex. Among modifiable lifestyle factors, physical inactivity was the most important risk factor across all age groups. These findings highlight the need to prioritize comorbidity management and physical activity promotion to prevent dementia in hypertensive patients.
**Background:** Dementia is a growing global health burden, and patients with hypertension are at higher risk for developing dementia. Identifying and prioritizing modifiable risk factors is essential for primary prevention, especially given the lack of effective therapies. This study aimed to determine the relative importance of various risk factors for incident dementia in a large cohort of treated hypertensive patients.
**Methods:** This population-based cohort study used data from the Korean National Health Insurance Service (NHIS) National Health examinee database. Eligible individuals were adults aged 40-79 years with hypertension (defined by ICD-10 codes and antihypertensive medication claims) who underwent health screening between 2007 and 2009. Exclusion criteria included prior stroke or dementia (2002-2006), missing screening data, or missing covariates. The final cohort comprised 650,476 individuals. Dementia was defined as a new diagnosis with ICD-10 codes for Alzheimer's disease (F00 or G30), vascular dementia (F01), or other dementia (F02, F03, G31) plus prescription of anti-dementia medications (rivastigmine, galantamine, memantine, or donepezil). The positive predictive value of this definition was 94.7%. Follow-up continued until dementia diagnosis, death, or December 2017 (mean 9.5 ± 2.8 years). The relative importance of risk factors was assessed using the estimated explained relative risk (R²) from Cox proportional hazards models. Risk factors included age (40-59, 60-69, 70-79 years), sex, comorbidity burden (Charlson Comorbidity Index ≥75th percentile vs. <75th percentile), physical inactivity (never vs. ≥1 time/week), smoking (current vs. others), alcohol consumption (≥10 g/day vs. <10 g/day), obesity (BMI ≥27.5 kg/m² vs. <27.5 kg/m²), statin use, elevated fasting glucose (≥140 mg/dL vs. <140 mg/dL), BP control (systolic BP ≥130 mmHg vs. <130 mmHg), hypertension duration (≥5 years vs. <5 years), elevated total cholesterol (≥200 mg/dL vs. <200 mg/dL), and low income (lowest quartile vs. others). Subgroup analyses were performed by age group (40-59, 60-69, 70-79 years).
**Key Results:** During a mean follow-up of 9.5 ± 2.8 years, 57,112 cases of dementia occurred. The strongest predictor was age (R² = 0.0504), followed by comorbidity burden (R² = 0.0023) and female sex (R² = 0.0022). Among lifestyle factors, physical inactivity had the highest R² (0.00070), followed by smoking (0.00024), alcohol consumption (0.00021), and obesity (0.00020). Other factors (statin use, elevated fasting glucose, BP control, hypertension duration, elevated cholesterol, low income) had lower R² values. In age-stratified analyses, physical inactivity was among the three most important risk factors in all age groups. For ages 40-59, the top three were comorbidity, obesity, and physical inactivity. For ages 60-69, they were obesity, physical inactivity, and alcohol consumption. For ages 70-79, they were physical inactivity, alcohol consumption, and obesity.
**Clinical Implications:** This study provides a prioritized list of risk factors for dementia in hypertensive patients, emphasizing that while age is non-modifiable, comorbidity burden and lifestyle factors (especially physical inactivity) are highly important and potentially modifiable. The findings support aggressive management of comorbidities and promotion of physical activity across all age groups. Smoking cessation, limiting alcohol consumption (≥10 g/day was a risk factor), and maintaining a BMI <27.5 kg/m² are also recommended. The age-specific results suggest that in younger adults (40-59), comorbidity and obesity are particularly important, while in older adults (≥60), physical inactivity and alcohol consumption rank higher. Limitations include the retrospective design, lack of a non-hypertensive comparator group, absence of data on family history or genetic factors, and inability to differentiate risk factors by dementia subtype. The R² values were low overall, indicating that many unmeasured factors contribute to dementia risk. Nonetheless, this large nationwide study provides actionable evidence for public health strategies targeting dementia prevention in hypertensive populations.