Dementia Risk Increased With Nonalcoholic Fatty Liver Disease, Additional Cardiovascular Comorbidities

Ying Shang, PhD, MSc

Data from a population-based cohort of Swedish patients aged 65 years and older showed a modest association between nonalcoholic fatty liver disease (NAFLD) and the development of vascular and nonvascular dementia.¹ The presence of comorbid cardiovascular diseases such as stroke or heart disease appeared to exacerbate the impact of NAFLD on dementia risk.

During a median follow-up of 5.5 years, 145 (5.0%) patients with NAFLD, and 1291 (4.6%) individuals of the matched cohort developed dementia, which translated to an HR of 1.86 (95% CI, 1.55-2.25) for dementia associated with NAFLD. The association between NAFLD and dementia was attenuated after adjusting for metabolic disorders (aHR, 1.64; 95% CI, 1.29-2.07) and further reduced but still statistically significant after additionally adjusting for depression, stroke, and heart disease (aHR, 1.30; 95% CI, 1.10-1.72).

Previous studies have suggested that NAFLD is associated with metabolic disorders and additional components of the metabolic syndrome, such as type 2 diabetes or hypertension, which have been associated with a higher risk of dementia. Led by Ying Shang, PhD, MSc, postdoctoral researcher, Karolinska Institutet, this study aimed to see whether NAFLD contributes to dementia risk independent of these factors, as well as examine the role of comorbid cardiovascular disease on these associations.

A total of 2898 patients with NAFLD and 28357 matched controls were identified from the National Patient Register between 1987 and 2016 and included in the analysis. Patients with a diagnosis of NAFLD prior to age 65 were excluded because 80% of NAFLD diagnoses were made after 2001 and the median age of dementia diagnosis in Sweden is 85 years. The study also excluded those with a prevalent or subclinical dementia, and those with other liver diseases on or prior to the index date.

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In general, patients with NAFLD were more likely to have metabolic disorders, cardiovascular comorbidities, and depression, than the matched cohort (P <.001 for all). Regarding dementia subtypes, Cox regression models suggested that NAFLD is related to a somewhat higher rate of vascular dementia (aHR, 1.15; 95% CI, 0.78-1.70). The risk of dementia was similar across sex and was attenuated for those in a small subgroup (n = 108; 3.7%) diagnosed with NAFLD after age 85 (aHR, 1.08; 95% CI, 0.55-2.22).

The 5-year cumulative incidence of all-cause dementia was 3.6% for patients with NAFLD and 2.0% for the matched cohort. Ten years from the index date, 7.5% patients with NAFLD and 5.5% of the matched cohort developed all-cause dementia. Regarding vascular dementia, the 10-year cumulative incidence was 1.9% for patients with NAFLD and 1.1% for the matched cohort.

Statistically significant interactions were observed between stroke and NAFLD (P = .03) but not heart disease (HD) and NAFLD (P = .57). In comparison with the matched cohort, stratified analysis revealed higher risk of dementia of those with NAFLD without stroke. Relative to the matched cohort without NAFLD, HD, or stroke, those who did have NAFLD, stroke, or HD alone had higher rates of incident dementia in the fully adjusted model (NAFLD only: aHR, 1.42 [95% CI, 1.10-1.82]; HD only: aHR, 1.90; 95% CI, 1.43-2.53]; stroke only: aHR, 2.12 [95% CI, 1.64-2.74]). Patients who had at least 2 diseases were associated with a 2-fold increased rate of dementia (aHR, 2.00; 95% CI, 1.52-2.62).

REFERENCE
1. Shang Y, Widman L, Hagstrom H. Nonalcoholic fatty liver disease and risk of dementia: a population-based cohort study. Neurology. Published July 13, 2022. doi:10.1212/WNL.0000000000200853