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Atrial fibrillation, overt stroke, and cognitive function


Evidence suggests that atrial fibrillation ( AF ) is associated with a higher risk for cognitive impairment and dementia, with or without a history of clinical stroke.
Two meta-analyses that included both cross-sectional and prospective studies specifically examined the incidence of dementia in patients with atrial fibrillation and strokes.
These meta-analyses found similar estimates of the risk ratios of cognitive impairment or dementia of 2.4324 and 2.7025.

It is uncertain whether or not the risk of cognitive impairment and dementia varies in paroxysmal compared with persistent atrial fibrillation.
Many of the studies examining atrial fibrillation type were small and underpowered and the factors that impact progression, such as rhythm control approaches and physician approach to the patient management, can introduce study biases.

In a small hypothesis generating cross-sectional study from the Atherosclerosis Risk in Communities ( ARIC ) Cohort persistent but not paroxysmal atrial fibrillation classified by ambulatory telemetry monitoring was associated with lower cognitive function.
Another small cross-sectional study reported that cognitive performance did not significantly differ by atrial fibrillation burden, but the number of subclinical cerebral ischaemia areas was higher in individuals with persistent compared with paroxysmal atrial fibrillation.

More conclusive understanding of the relation of atrial fibrillation burden to cognitive decline and dementia will require larger and longitudinal studies.
The relation between atrial fibrillation type and cognitive impairment and dementia is further complicated by the sometimes arbitrary definition of the atrial fibrillation type in the individual patient.

Unfortunately there are no randomized data examining the efficacy of therapies and in particular of individualized management to prevent dementia in individuals with atrial fibrillation.

Of interest, the Framingham Heart Study has examined temporal trends in the incidence of dementia and noted that the risk of dementia associated with atrial fibrillation declined over three decades ( 1970s to the early 2010s ).

One speculation is that improved anticoagulation and treatment of risk factors were responsible for the declining incidence of dementia in individuals with atrial fibrillation.
Another piece of inferential evidence, supporting the benefit of preventing stroke as a strategy to prevent dementia in individuals with atrial fibrillation, are observational meta-analyses.
In individuals with atrial fibrillation but without stroke at baseline the risk of dementia and cognitive decline is more modest [ relative risk ( RR ) 1.37, 95% confidence interval ( CI ) 1.08–1.73 ] than in individuals with both atrial fibrillation and a history of stroke ( RR 2.7, 95% CI 1.82–4.00 ).

Systemic anticoagulation remains the cornerstone of stroke prevention treatment. By meta-analysis, adjusted-dose Warfarin is associated with a 64% ( 95% CI 49–74% ) significantly lower risk of stroke, whereas Aspirin alone was associated with a 19% ( 95% CI −1 to 35% ) non-significant lower stroke risk.
In studies comparing Warfarin and Aspirin, Warfarin was associated with a 38% ( 95% CI 18–52% ) stroke reduction, when compared with Aspirin alone.

A meta-analysis of the four randomized trials comparing the non-vitamin K antagonist oral anticoagulants ( NOACs ) to Warfarin, demonstrated that the NOACs were associated with a significant risk reduction ( RR 0.81, 95% CI 0.73–0.91 ) in overall stroke and systemic emboli, in part driven by the significant risk reduction ( RR 0.48, 95% CI 0.39–0.59 ) in haemorrhagic stroke.

Since a prior stroke represents the strongest predictor of stroke recurrence, all patients who have atrial fibrillation and have had an ischaemic stroke should be anticoagulated, unless an absolute contraindication exists.
Of interest, a recent observational study using a propensity score-matched analysis reported that in individuals with a history of atrial fibrillation and dementia, persistent use of Warfarin therapy was uncommon ( 16% ), but was associated with the prevention of stroke [ hazard ratio, HR=0.74, 95% CI 0.54–0.996; P = 0.047 ] and death ( HR 0.72, 95% CI 0.67–0.87; P less than 0.001 ).

A recent updated meta-analysis reported a significant reduction of stroke, stroke or systemic embolism, haemorrhagic stroke, and intracranial bleeding in atrial fibrillation patients with previous stroke or transient ischaemic attack ( TIA ) receiving NOACs compared with Warfarin. ( Xagena )

Source: Dagres N et al, Europace, 2018

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