Is there an association between atrial fibrillation onset age and incident dementia?

By Neha MathurReviewed by Lily Ramsey, LLMNov 13 2023

In a recent prospective cohort study published in Jama Network Open, researchers examine whether younger age at atrial fibrillation (AF) diagnosis is associated with a higher risk of incident dementia.

Study: Age at Diagnosis of Atrial Fibrillation and Incident Dementia. Image Credit: pikselstock/Shutterstock.com

Background

The cases of all types of dementia are increasing with the increasing life expectancy of the global population.

It is the world's newest health challenge, considering its high mortality and lack of effective pharmacological interventions that could prevent or reverse pathological damage and neuronal degeneration occurring in dementia.

AF, a kind of cardiac arrhythmia, is quite common worldwide and shares various similarities with dementia. For instance, AF causes stroke, which is a proven risk factor for dementia.

Advanced age and metabolic conditions, such as diabetes and obesity, are some of the other shared risk factors for AF and dementia.

Although epidemiological evidence suggests that the risks of cognitive deficits and dementia are higher in people with AF, concrete proof that having AF diagnosed in early life (before 65 years) increases the likelihood of developing dementia later is lacking.

About the study

In this study, researchers pursued evidence of the plausible association between new-onset AF and incident dementia using data from the United Kingdom Biobank (UKB).

In total, 502,411 people from all across England, Wales, and Scotland aged 40-69 years registered with the National Health Service (NHS), UK, and living within 25 miles of at least one of the UKB assessment centers consented to participate in this study. 

They ascertained AF and age at AF diagnosis and all cases of all-cause dementia, vascular dementia (VD), and Alzheimer's disease (AD). The study covariates were age, sex, ethnicity, educational level, current drinking and physical activity levels, and depressed mood.

On their baseline visit between 2006 and 2010, they provided their biological samples and physical measures. Additionally, they participated in a touchscreen questionnaire and a verbal interview.

Of 502,411 participants recruited at baseline, the researchers included 433746 participants in the analyses exploring whether AF was associated with an increased risk of developing dementia.

First, they compared their baseline characteristics (AF vs. non-AF group) using a t-test (continuous variables) or chi-square test (categorical variables).

Further, they used data from 30,601 participants with AF at baseline or who developed AF during the follow-up period to investigate the association between the onset age of AF and incident dementia using Cox proportional hazard models, where the time gap between baseline and dementia occurrence, death, or follow-up served as the time scale. 

Specifically, this analysis covered three age groups: <65 years, 65-74 years, and ≥75 years, and its results were presented as hazard ratios (HRs) with 95% confidence intervals (CIs), which indicated the relative risk of an event (dementia or death) occurring in AF versus non-AF group.

Further, the researchers used propensity score matched data to investigate the association between AF and incident all-cause dementia, VD, and AD.

One participant from each of the three age groups was propensity-matched to two participants without AF (ratio of 1:2), resulting in 30,600 and 61,200 participants in the AF and AF-free groups.

These analyses adjusted for several variables, such as age, sex, ethnicity, education, and body mass index (BMI), to name a few.

The threshold of statistical significance for all statistical analyses was P< 0.05.

Results

The final analytical sample comprised 433,746 participants, of which 54.5% were female and 94.5% were White.

The average age of all the participants was 56.9 years. Relative to AF-free participants, those with AF were older (mean age 62.3 years), mostly men (63.4%), White (97%), and lower educational status (58.5%).

Dementia occurred in 1.36% (5,898 participants) of the study population over an average follow-up of 12.6 years.

The incidence rate of dementia was higher among participants with AF; accordingly, there were 1,031 dementia cases, including 320 VD and 350 AD, among 30,601 AF patients. 

So, while AF participants were at an elevated risk of developing all-cause dementia and VD than those without AF [adjusted HRs (aHRs), 1.42 and 2.06; 95% CI], the risk of developing AD was not as higher (aHR, 1.08; 95% CI).

Moreover, participants with younger age at AF diagnosis had a higher risk of developing all-cause dementia, AD, as well as VD (aHRs for every 10-year decline, 1.23, 1.27, 1.35; 95% CI).

In propensity score matching analyses, relative to individuals without AF, those with AF diagnosed at less than 65 years of age were at the highest risk of developing all-cause dementia (aHR, 1.82; 95% CI).

The risks increased for AF diagnoses between ages 65 and 74 years and ages ≥75 years (aHRs, 1.47 and 1.11; 95% CI). 

The researchers performed several sensitivity analyses; however, they observed that only ethnicity and apolipoprotein E4 (APOE4) carrier status might alter the association between new-onset AF age and dementia incidence.

Conclusions

Overall, the study results showing quantitative manifestation of the association between AF onset age and incident dementia highlights the need to prioritize monitoring of cognitive function among AF patients, especially those under 65 years at diagnosis.