- 1Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden firstname.lastname@example.org.
- 2Division of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
- 3Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden.
- 4Division of Hepatology, Department of Upper GI, Karolinska University Hospital, Stockholm, Sweden.
- 5Clinical Epidemiology Unit, Department of Medicine, Stockholm, Karolinska Institutet, Stockholm, Sweden.
Background and objectives: Non-alcoholic fatty liver disease (NAFLD) and dementia share common risk factors including metabolic disorders. However, whether NAFLD is associated with dementia risk is unclear. We investigated the association between NAFLD and dementia risk as well as the role of cardiovascular complications including heart disease and stroke.
Methods: In this population-based matched cohort study, we identified all Swedish patients aged ≥65 years with NAFLD identified from the National Patient Register (NPR) between 1987 and 2016. These were matched with up to ten reference individuals from the general population on age, sex, and municipality at the year of diagnosis. Incident dementia diagnosis was derived from the NPR or the Cause of Death Register until 2016. Adjusted hazard ratios (aHR) and 95% confidence intervals (CI) were estimated with Cox regression models.
Results: A total of 2898 patients with NAFLD and 28357 matched controls were identified (median age at entry, interquartile range [IQR], 70 ; 55.1% female). During a median follow-up of 5.5 years (IQR: 8.5 years), 145 (5.0%) patients with NAFLD and 1291 (4.6%) reference individuals were diagnosed with dementia. Compared to the reference individuals, patients with NAFLD had higher rates of dementia (aHR 1.38, 95% CI 1.10-1.72) and vascular dementia (aHR 1.44, 95% CI 0.96-2.23, p=0.07). Comorbid NAFLD and either heart disease (aHR 1.50 95% 1.08-2.05) or stroke (aHR 2.60 95% CI 1.95-3.47) conferred a greater risk of dementia.
Discussion: NAFLD had a modest association with increased rates of dementia. This was stronger among patients with NAFLD diagnosed with cardiovascular comorbidities.
Classification of evidence: This study provides Class II evidence that non-alcoholic fatty liver disease is associated with the development of vascular and non-vascular dementia.