Background/Purpose: Alzheimer’s disease and related dementias have an immense disease burden, with predicted continuous increase in incidence and prevalence. Systemic inflammation plays a major role in dementia, as well as in cardiovascular and cerebrovascular disease (CVD). Both RA and CVD have been reported to independently increase the risk of dementia, but little is known on the interplay between them on cognitive decline.

Methods: In this retrospective population-based study, patients with incident RA after age 50 who met 1987 classification criteria between 1980-2014, with no previous diagnosis of dementia prior to index date were included. RA cases were matched 1:1 with non-RA controls on age, sex and calendar year of index.

Data on CVD risk factors (i.e., hypertension, diabetes mellitus, hyperlipidemia, body mass index [BMI]) and CVD were abstracted from the medical records at baseline and throughout the follow-up. CVD was defined as coronary heart disease (including angina pectoris, coronary artery disease, myocardial infarction, coronary revascularization procedures), heart failure, cerebrovascular accident or transient ischemic attack. Dementia was defined as two relevant ICD-9/ICD-10 codes at least 30 days apart. Mediation analysis was carried out with RA as the exposure, CVD as a mediator, and dementia as the outcome. Models for both baseline mediation and time-dependent mediation were constructed.

Cox proportional-hazards models were used to estimate the adjusted hazard ratio (aHR) between RA and CVD along with the direct association between RA and dementia, with age, sex, education, hypertension, hyperlipidemia, and diabetes as covariates.

Results: 1,754 patients were included (877 RA cases and 877 non-RA controls). Mean age at index date was 64.7 years, with 65% females in both groups. At baseline, hypertension, hyperlipidemia, and diabetes were more prevalent in the RA cohort, with mean BMI similar in both cohorts. Prevalence of any CVD at baseline was not significantly different between the two groups (20.3% in RA vs 21.4% in non-RA, p=0.56). Mediation analysis with CVD at baseline as the mediator showed no significant mediated effect between the two cohorts.

During follow-up, 139 patients with RA and 125 individuals without RA developed dementia and 444 and 375, respectively, had any CVD. There was a significant association between RA and dementia both without (aHR 1.35, 95% CI 1.05-1.75) and with (aHR 1.33, 95% CI 1.04-1.72) CVD as a time-dependent mediator. There was a significant association between CVD on follow-up (aHR 2.02, 95% CI 1.53-2.67) with dementia risk. Yet, the mediation effect of any CVD on dementia was non-significant (p=0.69). There was a significant interaction between RA and CVD during the follow-up on dementia (aHR 1.89, 95% CI 1.12, 3.21; p=0.017).

Conclusion: Patients with RA are at a 35% increased risk of dementia, rising to 89% for patients who have both RA and CVD. We found no significant evidence that CVD acts as a mediator for the risk of dementia in RA. Yet, there is a significant synergistic effect of RA and CVD on dementia risk. This re-enforces the need for robust CVD prevention and dementia screening, along with optimization of disease activity in individuals with RA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-impact-of-cardiovascular-and-cerebrovascular-disease-on-the-risk-of-dementia-in-rheumatoid-arthritis-a-mediation-analysis/