Cardiac amyloidosis and the risk of Alzheimer's disease: a population-based nested case-control study

Abstract Background Transthyretin amyloidosis cardiomyopathy (ATTR-CM) and Alzheimer’s disease (AD) are age-related disorders characterized by pathological protein aggregation. Despite shared risk factors and mechanisms, the relationship between ATTR-CM and AD remains poorly understood. Methods We performed a population-based case–control study using the French National Health Data System from 2019 to 2023. Individuals aged 65 years or older diagnosed with ATTR-CM were matched with controls without ATTR-CM by age, sex, hypertension status, and area of residence. The main exposure was a diagnosis of AD within five years preceding the index date (ATTR-CM diagnosis or equivalent for controls). Conditional logistic regression estimated adjusted odds ratios (ORs) for the association between ATTR-CM and AD, accounting for major dementia risk factors including cardiovascular, metabolic, psychiatric, and lifestyle variables. Results Among 96,200 participants (19,240 ATTR-CM cases and 76,960 controls), 28,990 (30.6%) were women, and the mean (SD) age was 82.3 (6.6) years. The adjusted OR for AD among ATTR-CM patients was 0.65 (99% CI, 0.56–0.75), indicating a lower likelihood of AD compared with controls. Conclusions This large nationwide study suggests that ATTR-CM is associated with a reduced risk of AD, warranting further investigation into underlying biological mechanisms or possible diagnostic bias.