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Cerebral Microbleeds

Although the thromboembolic state of AF poses risks of microinfarction and tissue loss, cerebral microbleeds (CMBs) have been associated with AF as well. Atrial fibrillation conferred a 2.21 risk of CMB in stroke/transient ischemic attack patients.[39] When controlling for other small vessel manifestations (white matter hyperintensities and lacunar infarcts), the presence and number of CMB were related to global cognitive function; most of these were lobar in location again suggesting cerebral amyloid angiopathy as an etiology, but this study was in a broader population.[40]

Treatment

Anticoagulation

Oral anticoagulation (OAC) has been the mainstay treatment of AF and has documented benefit in stroke reduction.[41] People with AF have twice the risk of dying,[42] and only anticoagulation therapy has been demonstrated to reduce AF-related deaths.[43] Prescribing practices in "real-world" studies have shown a significant rate of anticoagulant omission, ranging from 34%[44] to 59%.[45] Although a number of clinical factors and bleeding risk characteristics may contribute to the low prescribing rate, no single impairment or geriatric characteristic was identified as a barrier to vitamin K antagonist use in an observational study of geriatric inpatients.[46] Cognitive impairment itself may be a patient- or prescriber-related barrier. A retrospective study of outpatients found that mild to moderate cognitive impairment was not associated with delayed time to achieve therapeutic anticoagulation, decreased anticoagulation stability, or more intensive clinic management.[47] However, van Deelen et al[48] found that patients with cognitive impairment and AF had a high likelihood of having poorer control of their international normalized ratio. A study of participants in the ACTIVE-W trial found that lower baseline Mini-Mental State Examination (MMSE) score correlated with poorer OAC control during 1.3 years of follow-up, even after controlling for other factors. Bleeding and vascular events were higher in patients with lower MMSE, but the risk was no longer significant after adjusting for time in therapeutic range, suggesting that, in patients with cognitive dysfunction, excess events could be reduced by improved anticoagulation.[49] However, the effect of anticoagulation on other aspects of cognitive decline has not been well established. In the AFFIRM trial, 72% of strokes occurred after warfarin was stopped or when the international normalized ratio was subtherapeutic.[50] A functional status substudy of AFFIRM showed no difference in MMSE scores between the 2 arms (rhythm vs rate control), regardless of actual rhythm at follow-up or warfarin use; however, OAC use in the substudy was markedly higher compared with previous studies and to the AFFIRM population.[51]

In post hoc analysis of 2 randomized controlled trials (ONTARGET and TRANSCEND), at a median follow-up of 56 months, patients with AF had an increased risk of cognitive decline, new dementia, independence in performing activities of daily living, and admission to a nursing home.[52] This association was independent of previous or incident clinical stroke, and similar to the Reykjavik study, anticoagulation had no effect on a composite outcome of decrease in MMSE score by ≥3 points, dementia, admission to a long-term care facility, and loss of independence in performing activities of daily living. In a very small case-controlled study, persons treated with warfarin had better scores on the Clinical Dementia Rating and Global Deterioration Scale than those treated with aspirin.[53] In a follow-up study to a cohort of the Coagulation Activation and Risk of Stroke in Atrial Fibrillation study of outpatients on OACs, dementia was reduced in patients taking warfarin, although this became of borderline significance after adjusting for age.[25] Decreasing quality of anticoagulation control, measured as categories of time in therapeutic range, was associated with increasing dementia risk (hazard ratio [HR] 2.57?5.34)[54] even after adjustment for age. This association was strongest in patients <80 years old. Cognitive function as a secondary outcome in the BAFTA trial randomizing patients to aspirin or warfarin showed no differences in MMSE scores at early (9 months) or late (33 months) follow-up; however, 43% of patients did not have MMSE data at 33 months, and patients were excluded once a stroke occurred.[55] The variable conclusions from these studies support a need for a well-designed trial measuring the effect of anticoagulation on the development of cognitive dysfunction in persons with AF.



Medical Therapy

A small randomized study examined the effects of combined atorvastatin and ezetimibe therapy on medial temporal lobe atrophy in persons with AF.[56] This study found greater atrophy and worse cognition in the placebo group. The authors also reported a reduction in inflammatory cytokines IL-1RA, IL-2, IL-9, IL-12, and macrophage inflammatory protein 1β, associated with improved cognition in several domains. Amygdala and hippocampal volume decreased for both arms, with significantly less decrease in left amygdala volume in the treatment arm; no correlations were found to changes in white matter lesions.[57] Previous studies in general populations with hypercholesterolemia have suggested that cognitive function decline can be prevented in middle-aged persons but not in older persons.[58] A study of the effect of secondary prevention for vascular events on cognitive function after stroke showed a benefit of antihypertensive therapies and optimal medication therapy for poststroke patients without a history of AF but no benefit in those with AF ().[59]


Date: 2016-06-13; view: 7


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Table I. Summary of reviews and meta-analyses of association between AF and cognitive impairment | Cognitive Screening and Future Directions
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