Association of Abnormal P-Wave Indices With Dementia and Cognitive Decline Over 25 Years: ARIC-NCS (The Atherosclerosis Risk in Communities Neurocognitive Study)

Abstract

Background Abnormal P-wave indices (PWIs)-reflecting underlying left atrial abnormality-are associated with increased risk of stroke independent of atrial fibrillation. We assessed whether abnormal PWIs are associated with incident dementia and greater cognitive decline, independent of atrial fibrillation and ischemic stroke. Methods and Results We included 13 714 participants (mean age, 57±6 years; 56% women; 23% black) who were followed for dementia through the end of 2015. (Abnormal P-wave terminal force in lead V1, ≥4000 μV×ms), abnormal P-wave axis (>75° or <0°), prolonged P-wave duration (>120 ms), and advanced interatrial block were determined from ECGs at visits 2 to 4. Dementia was adjudicated by an expert panel using data from cognitive tests and hospitalization International Classification of Diseases codes. Cognitive function was measured longitudinally using 3 neuropsychological tests. Cox proportional hazards models were used to assess the association between time-dependent abnormal PWIs with incident dementia. Linear regression models were used to evaluate PWIs with cognitive function over time. At the conclusion of the study, 19%, 16%, 28%, and 1.9% of participants had abnormal P-wave terminal force in lead V1, abnormal P-wave axis, prolonged P-wave duration, and advanced interatrial block, respectively. During mean follow-up of 18 years, there were 1390 (10%) dementia cases. All abnormal PWIs except advanced interatrial block were associated with an increased risk of dementia even after adjustment for incident atrial fibrillation and stroke: multivariable hazard ratio of abnormal P wave terminal force in lead V1=1.60, 95% CI, 1.41 to 2.83; abnormal P-wave axis, hazard ratio =1.36, 95% CI, 1.17 to 2.57; prolonged P-wave duration, hazard ratio=1.60, 95% CI, 1.42 to 1.80. Only abnormal P-wave terminal force in lead V1 was associated with greater decline in global cognition. Conclusions Abnormal PWIs are independently associated with an increased risk of dementia. This novel finding should be replicated in other cohorts and the underlying mechanisms should be evaluated.

Keywords: atrium; cognitive impairment; dementia; electrocardiography.

Figure 1

Flow diagram of study participants. ARIC indicates Atherosclerosis Risk in Communities; PWI, P‐wave indices.

Figure 2

Association between time‐dependent P‐wave indices and incident dementia, Atherosclerosis Risk in Communities Study, 1990–2015. The solid line depicts the hazard ratio, the gray area represents the 95% CI, and the histogram illustrates the distribution of P‐wave indices in the ARIC population. The hazard ratio crosses the dotted reference line at the median P‐wave value. The model is adjusted for age, race, and sex. A, Association between time‐dependent terminal force of the P‐wave in ECG lead V₁ and incident dementia. B, Association between time‐dependent P‐wave duration and incident dementia. C, Association between time‐dependent P‐wave axis and incident dementia. ARIC indicates Atherosclerosis Risk in Communities.

Figure 3

Cumulative risk of incident dementia by time‐dependent P‐wave indices, adjusting for the competing risk of death, Atherosclerosis Risk in Communities Study, 1990–2015. A, Cumulative risk of incident dementia by terminal force of the P wave in ECG lead V₁. B, Cumulative risk of incident dementia by P‐wave duration. C, Cumulative risk of incident dementia by P‐wave axis. D, Cummulative Risk of Dementia by aIAB. aIAB indicates advanced interatrial block.