The role of atrial fibrillation in cognitive aging : a population-based study

The role of atrial fibrillation (AF) in brain and cognitive aging (e.g., cognitive decline and dementia) is still unclear. In this doctoral thesis, we aimed to investigate the temporal trends and potential determinants of dementia incidence, the occurrence of AF and the pattern of use of antithrombotic drugs, the association of AF with cognitive decline and dementia, and the association of AF with various structural brain abnormalities among older adults. Data were derived from the population-based Kungsholmen Project (KP), the Swedish National study on Aging and Care in Kungsholmen (SNAC-K), and the SNAC-K MRI sub-study.

Study I: In the KP (1987-1989 to 1997-1998) and the SNAC-K (2001-2004 to 2010-2013) cohorts, 440 out of 1473 persons and 388 out of 1746 persons developed incident dementia, respectively. The incidence rate of dementia declined by 30% during the second decade (hazard ratio [HR] = 0.70; 95% confidence interval [CI]: 0.61-0.80). The decline was evident mainly among women and in people with low education. Vascular disorders and cognitive reserve factors explained only a small proportion of the decline (HR = 0.77, 95% CI: 0.65-0.90). Study II: In SNAC-K, 328 (9.8%) of 3363 persons were ascertained to have AF at baseline. The prevalence of AF increased with advancing age and was slightly higher than previously reported. From 2001-2004 to 2007-2010, the use of anticoagulant drugs substantially increased among people with AF, especially in people with high risk of stroke or low risk of bleeding. However, still two-thirds of those at high stroke risk remained untreated with anticoagulants. Study III: At baseline of SNAC-K, 243 (9.1%) of the 2685 dementia-free participants were identified to have AF. During the 9-year follow-up period, 279 (11.4%) people were ascertained to have incident AF and 399 (14.9%) developed incident dementia. As a time-varying variable, AF was associated with a faster annual decline in global cognition (β coefficient = -0.24, 95% CI: -0.31, -0.16) and a higher risk of all-cause dementia (HR = 1.40, 95% CI: 1.11-1.77) and vascular and mixed dementia (HR = 1.88, 95% CI: 1.09-3.23), but not Alzheimer’s disease. Among participants with AF, use of anticoagulant drugs, but not antiplatelets, was associated with a reduced risk of dementia (HR = 0.40, 95% CI: 0.18-0.92). Study IV: In the SNAC-K MRI sample, 39 (7.2%) of 540 people were identified to have AF at baseline. AF was associated with a higher odds ratio (OR) of the presence of cerebral infarcts (OR=3.98, 95% CI: 1.31-12.09). During the 6-year follow-up period, among 248 people who were free of cerebral infarcts, AF was associated with a faster increase in white matter hyperintensity volume (β coefficient = 0.45, 95% CI: 0.04-0.85) and lateral ventricular volume (β coefficient = 0.57, 95% CI: 0.13-1.02).

Conclusion: Dementia incidence had declined among older adults from the late 1980s to the early 2010s, and improved cardiovascular health and cognitive reserve could only partially explain the decline. In addition, AF is common in old age, and despite an increase in the use of anticoagulant drugs among older people with AF over time, still two-thirds of those with high risk of stroke remained untreated. Furthermore, AF is associated with an accelerated cognitive decline and a greater risk of dementia, and the use of anticoagulant drugs may prevent older patients with AF from developing dementia. Finally, AF is associated with a faster increase in white matter lesions and brain atrophy in the absence of cerebral infarcts.

List of scientific papers

I. Ding M, Qiu C, Rizzuto D, Grande G, Fratiglioni L. Tracing temporal trends in dementia incidence over 25 years in central Stockholm, Sweden. [Submitted]

II. Ding M, Fratiglioni L, Johnell K, Fastbom J, Ljungdahl M, Qiu C. Atrial fibrillation and use of antithrombotic medications in older people: a population-based study. Int J Cardiol. 2017;249:173-178.
https://doi.org/10.1016/j.ijcard.2017.07.012

III. Ding M, Fratiglioni L, Johnell K, Santoni G, Fastbom J, Ljungman P, Marengoni A, Qiu C. Atrial fibrillation, antithrombotic treatment, and cognitive aging: a population-based study. Neurology. 2018;91:e1732-e1740.
https://doi.org/10.1212/WNL.0000000000006456

IV. Ding M, Wang R, Kalpouzos G, Laukka EJ, Johnell K, Fratiglioni L, Qiu C. Atrial fibrillation and cerebral small vessel disease among older adults: a longitudinal population-based study. [Manuscript]