Cognitive Impairment in Atrial Fibrillation

Background: AF is mostly a disease of elderly. Up to 10% of people aged 80 years or older
suffer from this arrhythmia and the rate is projected to triple in the next 20 years (1).
Evidence is emerging that AF may increase the risk of all forms of dementia (2). Cerebral
hypoperfusion and the risk of cerebrovascular micro- and macro-embolism are plausible
explanations for the predisposition for cognitive decline in AF (1). Such insults may act
alone or in concert with other neuropathological changes common in the brain of older
individuals such as neuritic plaques or neurofibrillary tangles, in lowering cognitive
reserves and accelerating the onset of dementia (3).

Prior studies on AF and dementia have yielded conflicting results.

An earlier study provided evidence supporting an association between AF and increased
incidence of dementia in patients with stroke (4). In a prospective study conducted on
participants of ONTARGET and TRANSCEND trials, it was revealed that cognitive and functional
decline are important consequences of atrial fibrillation, even in the absence of overt
stroke (5). Another independent study, observed similar results for risk of dementia in AF in
participants with and without clinically recognized stroke during follow-up (3). Evidences
from a previous research demonstrated not only a significant association of AF with all forms
of dementia including Alzheimer's disease, but also higher mortality rate in patients with
coexistent dementia and AF (2). On the contrary, some studies did not find any significant
risk-association between AF and dementia (6-8).

These contradictory results compel the necessity for a prospective study on a large
population to obtain a clear understanding of the association between AF and cognitive
impairment. The potential association between the two conditions can have a very important
clinical implication; if there were a causal relationship between AF and dementia then the
different therapeutic strategies of AF may have differing influence on dementia risk (3).
Thus, this knowledge would facilitate in personalizing treatment approaches for individuals
with AF.

Anti-arrhythmic drugs are considered as the first line of therapy in AF and catheter ablation
is widely-recognized as the best option in drug-refractory cases. Recent published data
suggested that effective rhythm-control by catheter ablation reverses the risk of dementia in
AF (9). However, it was an epidemiologic study from a health-care database where ICD codes
were used to identify clinical dementia. Therefore, mischaracterization of the dementia
subtypes was a major possibility in their study.

None of the other currently ongoing studies or registries on AF ablation in US includes
dementia as one of the outcomes to be assessed. Therefore, our study will be the first to
examine the benefit of successful catheter ablation on cognitive function in AF patients by
directly assessing cognition using standardized instruments.

There are several standardized screening tools available to assess cognitive status, namely
Mini-Mental State Examination (MMSE), Cognitive Abilities Screening Instrument (CASI) and
Montreal cognitive assessment (MoCA). All have their strengths and limitations, but MoCA is
considered the most efficient because of its cross-cultural applicability and its higher
sensitivity for detecting mild cognitive impairments. In our study, MoCA would be used to
evaluate cognitive status in AF patients.

Besides MoCA, the following questionnaires will be used to assess other risk-factors for
cognitive impairment and quality of life in AF patients

1. Hospital anxiety and Depression scale (HAD): to evaluate anxiety and depression

2. Katz Index of Independence in Activities of Daily Living (ADL) and Lawton's Instrumental
Activities Of Daily Living Scale (IADL): to assess independent living skills

3. Multidimensional Scale of Perceived Social Support by Zimet et al: to appraise
perception of social-support in this study

4. International Physical Activity Questionnaire (IPAQ): to obtain internationally
comparable data on health-related physical activity

5. Atrial Fibrillation Effect on Quality-of-Life (AFEQT) questionnaire: to assess the
AF-specific changes in QoL before and after ablation

Study Objectives

Primary Objectives:

To evaluate the number of patients showing improvement or no-worsening in cognitive status at
2 years follow-up after catheter ablation or after the beginning of drug-therapy in
non-ablation group

Secondary Objectives:

1. Study the interaction between depression, social support and cognitive status

2. Evaluate the impact of social supports on the trajectory of dementia

3. Examine the correlation between physical activity and cognitive impairment

4. Assess the impact of arrhythmia recurrence on dementia across the control and the study
group

Study Design:

This prospective multicenter study will enroll 888 consecutive AF patients at different
centers in US, Asia and Europe.

Inclusion Criteria:

1. Age: ≥ 50 years, male or female subjects

2. Clinical diagnosis of AF

3. Ability to provide written, informed consent

Exclusion Criteria:

1. Patients with established dementia

2. MoCA score ≤ 17 on Montreal Cognitive Assessment (MoCA)

3. Use of illicit drugs

4. Alcohol use: >12 drinks/week on average

5. Clinical evidence of delirium or altered mental status

6. Medically unstable patients (acute/unstable or poorly controlled problems that would
demand focused, relatively urgent or emergent medical attention)