title: Atrial Fibrillation Patients Treated With Long-Term Warfarin Anticoagulation Have Higher Rates of All Dementia Types Compared With Patients Receiving Long-Term Warfarin for Other Indications.
abstract: The mechanisms behind the association of atrial fibrillation (AF) and dementia are unknown. We previously found a significantly increased risk of dementia in AF patients taking warfarin with a low percentage of time in therapeutic range. The purpose of this study was to determine the extent to which AF itself increases dementia risk, in addition to long-term anticoagulation exposure.
  
  
  
  A total of 10 537 patients anticoagulated with warfarin (target INR 2-3), managed by the Clinical Pharmacist Anticoagulation Service with no history of dementia were included. Warfarin indication was for AF (n=4460), thromboembolism (n=5868), and mechanical heart valve(s) (n=209). Patients in the latter 2 categories were included only if they had no prior history of AF. The primary outcome was dementia. Patients with AF were older and had higher rates of hypertension, diabetes, heart failure, and stroke. AF patients experienced higher rates of total dementia (5.8% versus 1.6%, P<0.0001), Alzheimer disease (2.8% versus 0.9%, P<0.0001), and vascular dementia (1.0% versus 0.2%, P<0.0001). A propensity analysis of 6030 patients was performed to account for baseline demographics differences. Long-term risk of dementia remained significant in AF patients compared with matched non-AF patients (total dementia: hazard ratio [HR]=2.42 [1.85-3.18], P<0.0001; Alzheimer: HR=2.04 [1.40-2.98], P<0.0001; senile: HR=2.46 [1.58-3.86], P<0.0001). Low percent therapeutic range compared with a higher percent therapeutic range was associated with dementia risk in both AF (26-50% versus >75%: HR=2.51, P=0.005) and non-AF groups (≤25% versus >75%: HR=3.92, P<0.0001).
  
  
  
  The presence of AF significantly increases risk of dementia, including Alzheimer's disease, compared with matched patients receiving warfarin anticoagulation for other reasons. Quality of anticoagulation management remains an important risk factor for dementia in all patients.
authors.affiliation: Intermountain Medical Center Heart Institute, Intermountain Medical Center, Murray, UT Department of Internal Medicine, Stanford University, Palo Alto, CA Thomas.bunch@imail.org.
authors.forename: T Jared
authors.initials: TJ
authors.lastname: Bunch
authors.affiliation: Intermountain Medical Center Heart Institute, Intermountain Medical Center, Murray, UT.
authors.forename: Heidi T
authors.initials: HT
authors.lastname: May
authors.affiliation: Intermountain Medical Center Heart Institute, Intermountain Medical Center, Murray, UT.
authors.forename: Tami L
authors.initials: TL
authors.lastname: Bair
authors.affiliation: Intermountain Medical Center Heart Institute, Intermountain Medical Center, Murray, UT.
authors.forename: Brian G
authors.initials: BG
authors.lastname: Crandall
authors.affiliation: Intermountain Medical Center Heart Institute, Intermountain Medical Center, Murray, UT.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Cutler
authors.affiliation: Intermountain Medical Center Heart Institute, Intermountain Medical Center, Murray, UT.
authors.forename: John D
authors.initials: JD
authors.lastname: Day
authors.affiliation: Intermountain Medical Center Heart Institute, Intermountain Medical Center, Murray, UT.
authors.forename: Victoria
authors.initials: V
authors.lastname: Jacobs
authors.affiliation: Intermountain Medical Center Heart Institute, Intermountain Medical Center, Murray, UT.
authors.forename: Charles
authors.initials: C
authors.lastname: Mallender
authors.affiliation: Intermountain Medical Center Heart Institute, Intermountain Medical Center, Murray, UT.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Osborn
authors.affiliation: Intermountain Medical Center Heart Institute, Intermountain Medical Center, Murray, UT.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Stevens
authors.affiliation: Intermountain Medical Center Heart Institute, Intermountain Medical Center, Murray, UT.
authors.forename: J Peter
authors.initials: JP
authors.lastname: Weiss
authors.affiliation: Intermountain Medical Center Heart Institute, Intermountain Medical Center, Murray, UT.
authors.forename: Scott C
authors.initials: SC
authors.lastname: Woller
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000453:epidemiology*; D000925:Anticoagulants / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000150:complications / Q000188:drug therapy* / Q000453:epidemiology; D003704:Dementia / Q000453:epidemiology; D015140:Dementia, Vascular / Q000453:epidemiology*; D005260:Female; D006350:Heart Valve Prosthesis; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D020521:Stroke / Q000209:etiology / Q000517:prevention & control*; D013923:Thromboembolism / Q000188:drug therapy* / Q000453:epidemiology; D014859:Warfarin / Q000627:therapeutic use*
chemical_list: D000925:Anticoagulants; D014859:Warfarin
keywords: Alzheimer disease; anticoagulant drugs; atrial fibrillation; cognition; dementia