It is well established that atrial fibrillation increases the risk of clinical stroke by four- to five-fold, and patients with a clinical history of stroke are at increased risk of developing dementia.
However, atrial fibrillation is also associated with cognitive dysfunction ranging from mild impairment to overt dementia, independently of clinical stroke as well as multiple shared risk factors.
It is also well established that atrial fibrillation and cognitive impairment share common risk factors, including advanced age, diabetes, hypertension, sleep apnoea, and chronic heart failure.
Moreover, data have demonstrated a significant ( 34% ) increase in the risk of cognitive impairment in patients with atrial fibrillation in the absence of clinical stroke, even after adjustment for shared risk factors.
Thus, additional mechanisms beyond clinically recognized stroke and shared risk factors may link atrial fibrillation and cognitive impairment. One of the leading potential mechanisms is the occurrence of silent cerebral infarcts, which occur significantly more frequently than clinical stroke and are particularly common in patients with atrial fibrillation.
Detection of cerebral ischaemic events on MRI is based on acute hyperintense lesions on DWI. Brain MRIs reveal evidence of silent cerebral infarcts in a significant percentage of patients with atrial fibrillation.
The incidence is related to specifications of MRI and depends on the definition applied.
Atrial fibrillation is associated with a more than two-fold increase in the risk of developing silent cerebral infarcts.
Although silent infarcts are not associated with clinically apparent acute neurologic deficits, data suggest a significant association between silent infarcts and the development of cognitive decline and dementia.
Silent infarcts in patients with atrial fibrillation are believed to be micro-embolic in origin and are identified as small, well-demarcated lesions, often in clusters, and are most prevalent in the frontal lobes.
The pattern of silent infarct distribution is similar to that seen in vascular dementia, in which most silent strokes affect frontal circuit components ( frontal cortex, basal ganglia, and thalamus ) that play an important role in executive functioning.
Thus, the term silent infarct is probably a misnomer.
Because of their small size and location away from speech and motor centres, these micro-injuries do not cause clinically apparent acute focal neurological deficits. However, with the accumulation of silent infarcts and associated repetitive brain injuries over time, micro-injuries may contribute to the development of cognitive impairment.
At least one study has specifically addressed the role of subclinical cerebrovascular disease as a mediator between atrial fibrillation and cognitive impairment.
In a subset of stroke-free participants in the ARIC study who underwent repeat brain MRI after approximately 12 years, atrial fibrillation was associated with cognitive decline only in those patients who had developed incident silent cerebral infarcts.
There is a paucity of evidence regarding the effect of anticoagulation on silent cerebral infarcts and the risk of cognitive impairment.
One recent study addressed this issue by evaluating the time in therapeutic range ( TTR ) as an indicator of the effectiveness of Warfarin anticoagulation in patients with atrial fibrillation. These investigators observed a consistent increase in the risk of dementia as the percentage of TTR decreased.
The association between Warfarin therapy and dementia was U-shaped, with increased risk of dementia among patients with overexposure and underexposure to Warfarin [ i.e. supra-therapeutic and sub-therapeutic international normalized ratios ( INRs ) ].
This may be due to cumulative brain injury from cerebral micro-bleeds and silent infarcts, respectively.
Recent observational data also suggest that delaying warfarin therapy in patients with atrial fibrillation and no history of dementia, including patients at low as well as high risk for stroke, significantly increases the risk for developing incident dementia.
Whether the use of the NOACs will offer greater protection than Warfarin in preventing atrial fibrillation-related cognitive impairment and dementia remains to be determined.
The significantly lower intracranial haemorrhage and micro-haemorrhage rates, the lower risk of mortality with intracranial haemorrhage with use of NOACs compared with Warfarin, coupled with comparable degrees of protection against thromboembolic stroke and substantially lower variability in therapeutic anticoagulation effect over time with NOACs, offer reasons to hypothesize that these agents may be advantageous to warfarin regarding protection against cognitive impairment in patients with atrial fibrillation but this requires confirmation. Initial findings seem to confirm this hypothesis. ( Xagena )
Source: Dagres N et al, Europace, 2018