TRINA LAPHARMD 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

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

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)

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

Objective

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

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 2008Participates were excluded from the study if

History of stroke at baseline History of transition ischemic attack

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

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

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

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

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

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

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