SAVE
YOUR
BRAIN
More reasons to optimize AF therapy
by Rick McGuire
W
hen it comes to the peripheral effects
of atrial fibrillation (AF), the body of
evidence keeps growing—so much so
you wonder what connection will be seen next.
One proving particularly alarming: there appears
to be a consistent association between AF and risk
of dementia, including Alzheimer’s disease, as well
as a suggestion of renal damage if AF is not appropriately controlled. While there may be several
mechanisms to explain this association—both AF
and dementia share multiple common risk factors,
for example—the therapies used to treat AF may
influence this risk, too, for better or worse.
In short, type and duration of anticoagulation,
as well as the choice between rhythm- and rate-
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control strategies, might all influence cognitive risk.
Also, we’re beginning to better understand the
risks of silent cerebral infarcts that are identified
in more than 40% of magnetic resonance imaging
(MRI) scans of patients with AF.1 Although silent
infarcts may not cause acute neurologic deficits, a
significant association between silent infarcts and
cognitive decline has been emerging.2
Independent Effects
Cardiologists appreciate that a vascular bed is a vascular bed whether it’s in the heart or the brain or
situated somewhere else along the peripheral way.
It was 18 years ago when investigators reported on
a cohort of 952 community-living men, aged 69
to 75 years, in Uppsala, Sweden, showing a strong
association between AF and low cognitive function
that was independent of stroke, high blood pressure, and diabetes.3 This followed the Rotterdam
Study, which first suggested that dementia, Alzheimer’s, and vascular dementia may be related to
AF even if no clinical strokes have occurred.
Subsequently, in the United States, Bunch et al.
studied 37,025 consecutive patients from the large
ongoing prospective Intermountain Heart Collaborative Study database.4 None of the patients had a
history of dementia and all patients were followed
for at least 5 years. Over the course of the study,
27% developed AF and 4.1% developed dementia.
AF was significantly and independently associated
with all dementia types (vascular, senile, Alzheimer’s disease, and nonspecified). Although dementia
is strongly associated with aging, the highest risk
of Alzheimer’s actually manifested in the youngest
group, those < 70 years of age (odds ratio: 2.30;
p = 0.001). There was a marked increased risk of
mortality overall, ranging from a hazard ratio (HR)
of 1.38 to 1.45 depending on the type of dementia
and all were statistically significant. The greatest
risk of death also was in the youngest cohort (< 70
years) with HRs ranging from 1.55 to 2.07.
Further evidence of jeopardy was suggested in
a more recent study evaluating the association of
prevalent and incident AF with incident dementia
in 6,514 participants from the prospective population-based Rotterdam Study; because they were
involved early in the investigation of this problem,
the study patients were assessed across a 20-year
period.5 Risk of dementia was strongly associated
with duration of exposure to AF in the younger
participants (< 67 years) (in the highest stratum of
exposure, HR: 3.30; p = 0.003 for trend) but not in
older participants (> 67 years; HR: 0.25).
But the final jeopardy answer may arise from a
new study that examined time to first diagnosis of
AF and then time to first diagnosis of any of nine
vascular events in a cohort of 4.3 million adults.6 The
United Kingdom investigators noted that previous
analyses of the relationship between AF and vascular
risk have largely focused on stroke, so they used a
nationally representative database of health records
to look more broadly at the effect of AF on vascular
events over a median follow-up of 6.9 years. Baseline
AF was associated with a 35% increased risk of subsequent vascular dementia and this combination was
associated with a three-fold risk of a fatal vascular
event (HR: 3.21; 95% confidence interval [CI]: 1.74
to 5.94).
Repetitive Cerebral Injury
CSWN talked to T. Jared Bunch, MD, at the recent
Heart Rhythm Society meeting in San Francisco,
CA. He is director of heart rhythm research at the
Intermountain Medical Center Heart Institute in
Salt Lake City, UT. Six years ago when his team first
reported their evidence suggesting a link between
AF and dementia, he said, “At that point, we started
to ask the question: Why do we see this association
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