Cardiometabolic diseases and risk of early-onset dementia: a population-based case-control study in Northern Italy

Background and aims: Early-onset dementia (EOD), defined by symptom onset before 65 years, has an uncertain etiology. Cardiovascular and metabolic diseases have been suggested to increase risk for EOD, but evidence remains limited and inconsistent. We investigated the extent to which history of cardiometabolic conditions is associated with EOD, and the extent to which the associations vary by sex, age at onset, and dementia subtype. Methods and results: We conducted a population-based case-control study in Modena, Northern Italy, including 334 EOD cases diagnosed from 1999 to 2021, and 1991 controls matched by sex, year of birth, and calendar year. Hospitalization records and drug prescriptions were retrieved from administrative databases to estimate cardiometabolic disease history before EOD onset. We estimated odds ratios (OR) and 95% confidence intervals (CI) using conditional logistic regression in the entire study population and within subgroups of age and sex. EOD cases showed higher rates of hospitalization for hypertension and diabetes. History of antidiabetic drugs (OR = 1.49, 95% CI 1.01-2.19), lipid-lowering agents (OR = 1.36, 95% CI 1.03-1.79), and antihypertensive drugs (OR = 1.47, 95% CI 0.93-2.32) was associated with higher EOD risk. Associations were stronger in males for antidiabetics (OR = 1.78, 95% CI 1.08-2.93) and antithrombotics (OR = 1.57, 95% CI 1.06-2.33), and in individuals <55 years for most antihypertensive classes. Non-Alzheimer's EOD generally showed higher associations with cardiovascular drug use than Alzheimer's type. Conclusions: The associations we found between cardiometabolic diseases and EOD, particularly non-Alzheimer's subtypes, are consistent with a role of cardiometabolic burden or shared etiologic factors in early cognitive decline.