LETTER/REPLIES

Continuum of Cognitive Impairment to StrokePossibly via Atrial FibrillationJacob I. Haft, MD

In their paper ‘‘Incident Cognitive Impairment Is Elevated in

the Stroke Belt: The REGARDS Study,’’1 the authors dem-

onstrate that the incidence of development of cognitive

impairment is higher in a population in which the incidence

of stroke is higher, suggesting that the mechanism for stroke

and cognitive impairment is the same (at least in some

patients) and that there may be a continuum between cogni-

tive impairment and stroke, that is, cognitive impairment is

an early and mild manifestation and stroke is an extreme

manifestation of the same underlying pathophysiologic ab-

normality. Previous studies, referenced in their paper, have

demonstrated a high incidence of the conventional risk fac-

tors for stroke in patients with cognitive impairment,

although not in the same population group. Were the indi-

vidual patients who developed cognitive impairment followed

longitudinally, and was there an increased incidence of subse-

quent overt stroke in these patients?

We have documented that atrial fibrillation, largely

intermittent and undiagnosed, is found in a high incidence

in stroke patients (at least 34.9% among ischemic stroke

patients with hypertension2) in whom all electrocardio-

grams (ECGs) in a >14-year ECG and clinical database

were reviewed, suggesting that intermittent atrial fibrilla-

tion may be the common mechanism whereby the conven-

tional risk factors for stroke cause stroke. Are data avail-

able on the incidence of atrial fibrillation in patients in

the Stroke Belt compared to the incidence of atrial fibrilla-

tion in patients in non-Stroke Belt states, and specifically,

are there data on the incidence of atrial fibrillation in the

patients in this study who developed cognitive impairment?

If there is a higher incidence of atrial fibrillation in these

patients, it might be advantageous to study patients with

increasing dementia with (1) magnetic resonance imaging

to identify those with multiple small silent infarcts and/or

(2) echocardiograms to find left atrial enlargement, left

ventricular enlargement, or low ejection fraction and to

identify patients most likely to benefit from long-term

monitoring to diagnose occult intermittent atrial fibrilla-

tion, who might then be considered for anticoagulation to

prevent overt stroke.

Potential Conflicts of Interest

Nothing to report.

Hackensack University Medical Center, Hackensack, NJ

References

1. Wadley VG, Unverzagt FW, McGuire LC, et al. Incident cognitiveimpairment is elevated in the Stroke Belt: the REGARDS study.Ann Neurol 2011;70:229–236.

2. Haft JI, Teichholz LE. Echocardiographic and clinical risk factorsfor atrial fibrillation in hypertensive patients with ischemic stroke.Am J Cardiol 2008;102:1348–1351.

DOI: 10.1002/ana.22618

ReplyVirginia G. Wadley, PhD,1 Virginia J. Howard, PhD,1

George Howard, DrPH (REGARDS Study PrincipalInvestigator),1 and Elsayed Z. Soliman, MD2

We appreciate the opportunity to respond to Dr Jacob

Haft’s queries and good suggestions. We agree with Dr Haft’s

perspective regarding the probability of shared pathways for

incidence of cognitive impairment and stroke, including atrial

fibrillation (AF). Our recent Annals of Neurology publication

was part of a larger effort to better understand multiple tradi-

tional and novel risk factors for cognitive decline and stroke.1

To this end, an analysis of Framingham stroke risk factors and

incident cognitive impairment in the REGARDS cohort is cur-

rently in press.2

With respect to Dr Haft’s questions as to whether indi-

viduals who developed cognitive impairment were followed lon-

gitudinally, and whether there was an increased incidence of

subsequent overt stroke in these participants, the answer to

both questions is yes. We recently reported that low cognitive

performance is a potent predictor of physician-adjudicated inci-

dent stroke among REGARDS participants younger than 72

years (ie, ages 45–72 years).3

In the population-based REGARDS study, AF was deter-

mined at baseline from study scheduled electrocardiograms

(ECGs) recorded in participants’ homes, as well as by self-

reported history of a previous physician diagnosis of AF. We have

shown in prior work that the prevalence of AF defined by ECG

plus self-report (ie, AF detected by both methods) is actually

lower in the Stroke Belt than the rest of the nation, although this

relationship was attenuated and no longer significant when defin-

ing AF by either self-report or ECG.4 Thus, our data do not sup-

port regional variations in AF that mirror regional differences in

incident cognitive impairment and stroke. Even so, we also have

demonstrated that irrespective of detection method, AF is a

strong and significant predictor of incident stroke (odd ratios

ranging from 1.41 to 1.90 depending on case definition).5 To

date we have not collected data for determining the geographic

distribution of incident or intermittent AF.

We appreciate Dr Haft’s suggestions for future research

directions as we continue our efforts to identify modifiable risk

factors for stroke and cognitive decline.

666 VC 2011 American Neurological Association