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TRINA LA PHARMD CANDIDATE OCT 18TH, 2011

Atrial Fibrillation & Risk of Dementia: A Prospective Cohort Study. Sascha Dublin, MD, PhD, Melissa L. Anderson, MS, et al. JAGS 2011; 59: 1369- 1375. TRINA LA PHARMD CANDIDATE OCT 18TH, 2011. Background study. By 2030, nearly one in five Americans will be aged 65 & older

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TRINA LA PHARMD CANDIDATE OCT 18TH, 2011

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  1. Atrial Fibrillation & Risk of Dementia: A Prospective Cohort Study Sascha Dublin, MD, PhD, Melissa L. Anderson, MS, et al. JAGS 2011; 59: 1369- 1375 TRINA LA PHARMD CANDIDATE OCT 18TH, 2011

  2. Background study • By 2030, nearly one in five Americans will be aged 65 & older • Cognitive impairment is one of the most feared conditions associated with aging • In the United States, the estimated costs of Alzheimer’s disease (AD) are $172 billion each year • Evidence is emerging that atrial fibrillation may contribute to dementia risk

  3. Background-Alzheimer’s disease • Definition: • A progressive dementia affecting cognition, behavior, & functional status with no known cause or cure • Patients eventually lose cognitive, analytical, and physical functioning, and the disease is ultimately fatal • Risk factors • Age • Family history • Apolipoprotein E (ApoE) gene • Diabetes • Vascular disease (particular stroke)

  4. Background-Atrial Fibrillation (AF) • AF is characterized as an extremely rapidly (400-600 atrial beats/min) & disorganized atrial activation • Risk factors • Advanced ages • Cardiovascular disease • Metabolic or hemodynamic derangements • COPD • Pulmonary embolism • Pneumonia

  5. Objective • Primary outcomes were incident all-cause dementia & possible or probable through the Adult Changes in Thought Study (ACT)

  6. Study Design & Setting • A population-based cohort study set within Group Health (GH), an integrated healthcare delivery system • ACT recruited community-dwelling adults without dementia aged 65 & older • The study was conducted from 1994 to 2008 • Participates were excluded from the study if • History of stroke at baseline • History of transition ischemic attack

  7. Measurement and Population • Measurement: • AF was identified if there were at least 2 clinical encounters with ICD-9 codes for AF or atrial flutter on different days within a 12 month period • Participants were screened every 2 years using the Cognitive Abilities Screening Instrument (range 0-100), with detailed neuropsychological & clinical assessment of those scoring <86 • Review of results of recent cranial imaging if available • Use Diagnostic & Statistical Manual of Mental Disorder criteria to identify cases of dementia

  8. Results • 3743 participated but 2781 qualified to be in sensitivity analysis • At baseline: • AF: 132 (4.3%) participants • Mean of 6.8 years of follow-up: • AF: 370 (12.2%) more participants • 572 participants (18.8%) developed dementia • 499 participants with AD • The adjusted hazard ratio associated with AF • 1.38 (95% CI: 1.10-1.73) for all-cause dementia • 1.5 (95% CI: 1.16-1.94) for possible or probable AD • Results were similar for participants with & without clinically recognized stroke during follow-up & in sensitivity analyses examining only probable AD

  9. Author’s conclusion • AF is associated with higher risk of developing AD & dementia • Future studies should examine whether specific treatments, including optimal anticoagulation, can decrease this risk

  10. Discussion • In this population-based study of older adults • AF was associated with a 40% to 50% higher risk of AD & all-cause dementia, independent of stroke • This higher risk persisted after adjustment for many CV risk factors & diseases

  11. Some biological mechanisms that are associated AF & Dementia • AF • incomplete atrial emptying, which may lead to thrombus formation, resulting in systemic embolization in the brain & causing stroke • Silent cerebral emboli • Cerebral hypoperfusion due to irregular heart beat • These mechanism may be associated with other neuropathological entities associated with dementia • Neurofibrillary tangles • Lewy bodies • Hippocampal sclerosis • AF & dementia may share underlying risk factors • Inflammation

  12. Other Relative Studies • Three of eight longitudinal studies reported that participants with AF were at higher risk of dementia • One study found this association only in participants with mild cognitive impairment • Another found an association at 5 years of follow up • Five longitudinal studies found no association • The studies that found an association examined a younger population than those that found no associations

  13. Study limitations • The methods used to detect AF & dementia varied widely • Some studies used measures of dementia that have poor sensitivity or specific • Diagnoses of dementia & AD were based on clinical criteria without neuro-imaging studies • Cases of vascular or mixed dementia may have been misclassified as AD

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