30 Oct, 15 | by EBM
By Dr. Geoffrey Modest
The studies on the relationship between atrial fibrillation (AF) and dementia are inconsistent. This long-term, prospective population-based observational Rotterdam Study provided insight into this relationship (see doi:10.1001/jamaneurol.2015.2161).
- 6514 participants (mean age 68, 59% female, BMI 26, 10% diabetic, BP 139/74, chol/HDL ratio of 290/54, 42% former/23% current smokers, 8% with coronary artery disease, and 3% with heart failure)
- 318 (5%) had prevalent AF at start of study; 994 (15%) developed incident dementia over 20 years of follow-up
- Prevalent AF was associated with increased risk of dementia, with HR 1.33 (1.02-1.73), meaning a 33% increase vs those without prevalence AF
- Of 6196 without prevalent AF (79K person-years of follow-up), 723 (12%) developed incident AF and 932 (15%) developed incident dementia
- Incident AF was associated with an increased risk of dementia in those <67yo, with HR 1.81 (1.11-2.94), but was not significant in those >67yo
- The risk of dementia was strongly related to the duration of exposure to AF: those younger patients with the longest exposure had HR 3.30 (1.16-9.38, with p=0.003 for trend), though not in those >67yo
- The above relationships were independent of clinical stroke, and didn’t vary by whether the dementia was classified as “Alzheimer” or “non-Alzheimer”
The above study found an impressive relationship between AF and dementia in those <67yo, with an apparent dose-response curve (the longer the AF exposure, the more dementia). There are some important caveats:
- The definition of dementia was basically a clinical one, relying on the MIni-Mental State Exam and Geriatric Mental State Schedule, with further clinical differentiation of Alzheimer vs non-Alzheimer. These tests are insensitive to picking up early dementia, especially in high-functioning adults
- There was no systematic neuroimaging, so unclear if there were either subclinical strokes, or even asymptomatic emboli (lacunar strokes are associated with cognitive decline)
- The above study did not have any information about whether the patients with AF were anticoagulated (nor how good the level of anticoagulation was)
- It is difficult to attribute causality in an observational study: was the issue that the AF caused cerebral hypoperfusion (AF is associated with decreased cardiac output) or small cerebral emboli leading to cognitive decline? Or that both AF and cognitive decline share similar causes (those who had AF were more likely to be smokers, have lower HDL levels, be on treatment for hypertension, be diabetics)?
- AF is often undetected in asymptomatic individuals, since it is often intermittent. In a study as the above one, with clinic visits/EKGs done every 3-4 years, we may well miss asymptomatic intermittent AF. Perhaps we should have a more aggressive approach to AF diagnosis?? 24 or more hour monitoring every year??
So, the real issues in primary care are:
- AF is really common and increasing as the population ages
- The data on rhythm control (e.g., reverting to normal sinus rhythm) vs rate control (just controlling the ventricular rate) did not assess long-term cognitive issues (e.g. the AFFIRM and RACE trials, which somewhat favored rate control, basically assessed mortality, strokes/hemorrhages, serious arrhythmias, and used somewhat toxic antiarrhythmics and did not maintain full anticoagulation in those with rhythm control). It is certainly possible that restoration of normal sinus rhythm is in fact better in the prevention of cognitive decline.
- But, it is hard to maintain normal sinus rhythm with these pretty toxic meds. Even with radiofrequency ablation, there are not-so-infrequent AF recurrences (meta-analysis of ablation found only about 50% were in NSR after 3 years with a single ablation, though increases to about 80% with multiple ablations, though ablations themselves are also associated with emboli –e.g., see JACC 2013; 62:531 or Circ 2010; 122:1667.) and who knows how sustained normal rhythm will actually be in longer-term studies? Or even if some who have “NSR” still have occasional episodes of AF which could be associated with small, inapparent emboli? Maybe we should aim for sinus rhythm but continue with anticoagulation??
- And, it would be very interesting to know if either rhythm control (as best as we can measure it) or adequate anticoagulation diminishes cognitive decline (one possible study might be in those with low CHA2DS2-VASc scores, who are not generally given anticoagulation, to be randomized to anticoagulation vs not, to see if there is a long-term cognitive difference. There is a study lending some support to this — those in AF on anticoagulants and more often in therapeutic range had less dementia –see Heart Rhythm 2014: 11:2206 — though this was not a randomized control study, so there may have been important differences in those achieving better control than the others.)
- But, the finding above that the duration of AF being associated with more cognitive decline, is somewhat reassuring since it is likely that those with less evident AF seem to be at lower risk, supporting the concept that decreasing the numbers of episodes of AF may be helpful.
- In some ways the real value of a quick-and-dirty study as the Rotterdam one above serves to raise a much bigger issue: we perhaps should not be so complacent with just achieving rate control, the current general approach, but should pursue studies to see if another very important endpoint (cognitive decline) might be better achieved by more aggressive attempts to reinstate sinus rhythm.