Researchers report that structural or functional abnormalities within the heart’s left atrium, with or without symptoms, may increase a person’s risk of developing dementia later in life by 35%. The scientists, who published their study (“Risk of Dementia Associated With Atrial Cardiopathy: The ARIC Study”) in the Journal of the American Heart Association, noted that the dementia risk increased even among those who did not experience atrial fibrillation or stroke, two conditions known to be associated with dementia.

“The contribution of atrial cardiopathy to dementia risk is uncharacterized. We aimed to evaluate the association of atrial cardiopathy with incident dementia and potential mediation by atrial fibrillation (AF) and stroke,” wrote the investigators.

“We conducted a prospective cohort analysis of participants in the ARIC (Atherosclerosis Risk in Communities) study attending visit 5 (2011–2013). We used Cox regression to determine the association between atrial cardiopathy and risk of dementia. Structural equation modeling methods were used to determine potential mediation by AF and/or stroke.

“Atrial cardiopathy was defined if ≥1 of the following at visit 5: P‐wave terminal force >5000 mV·ms in ECG lead V1, NT‐proBNP (N‐terminal pro–brain natriuretic peptide) >250 pg/mL or left atrial volume index ≥34 mL/m2 by transthoracic echocardiography. We repeated our analysis necessitating ≥2 markers to define atrial cardiopathy. The prevalence of atrial cardiopathy was 34% in the 5078 participants (mean age 75 years, 59% female, 21% Black adults), with 763 participants developing dementia.

“Atrial cardiopathy was significantly associated with dementia (adjusted HR, 1.35 [95% CI, 1.16–1.58]), with strengthening of the effect estimate when necessitating ≥2 biomarkers (adjusted HR, 1.54 [95% CI, 1.25–1.89]). There was an increased risk of dementia among those with atrial cardiopathy when excluding those with AF (adjusted HR, 1.31 [95% CI, 1.12–1.55]) or stroke (adjusted HR, 1.28 [95% CI, 1.09–1.52]). The proportion of the effect mediated by AF was 4% (P=0.005), and 9% was mediated by stroke (P=0.048).

“Atrial cardiopathy was significantly associated with an increased risk of dementia, with only a small percent mediation of the effect by AF or stroke.”

More insight and better understanding needed

The study results highlight the need to get a better understanding of the relationship and mechanisms between a state of atrial dysfunction, that may be subclinical (not presenting symptoms) and the newly uncovered association with dementia, according to the researchers.

Participants in the current analysis were part of a larger study group of more than 15,000 people originally recruited for the ongoing ARIC study, which began in 1987 to research heart health in people living within four diverse communities throughout the United States.

Researchers evaluated cognitive decline in all participants with a comprehensive neuropsychological test battery from the Uniform Data Set of the Alzheimer’s Disease Centers program of the National Institute on Aging, as well an informant interview in a subset of participants. Informant interviews are a screening test of questions, such as the Eight-Item Informant Interview to Differentiate Between Aging and Dementia, given to a spouse, adult child, or close friend of the adult being evaluated for cognitive decline.

The neuropsychological test battery consists of brief measures of processing speed, episodic memory, language, attention, and executive function. A diagnosis of dementia was generated based on testing results by a computer diagnostic algorithm and then decided upon by an expert based on the Diagnostic and Statistical Manual of Mental Disorders and the criteria outlined by the National Institutes of Health.

Hospital discharge codes (obtained as part of the ARIC study either directly from hospital discharge indices or from an indexing service or from an indexing service) and death certificate data, obtained as part of the ARIC study from the Automated Classification of Medical Entities system, were also included to assess participants’ cognitive status.

Additionally, cardiac evaluation, including echocardiography, electrocardiography, and blood work, was conducted to assess the size and function of the left atrium of the heart to check for signs of atrial cardiopathy.

The analysis of the collective health data found that throughout the more than 30 years of follow-up, 763 people developed dementia, and 1,709 had atrial cardiopathy. The participants with atrial cardiopathy appeared to be 35% more likely to develop dementia.

When the researchers adjusted for participants who experienced atrial fibrillation and stroke, even after accounting for other vascular risks, they still observed a respective 31% and 28% increase in dementia risk in patients with atrial cardiopathy. The researchers suggested that a state of atrial cardiopathy leading to dementia is not a result of atrial fibrillation or stroke alone.

While the researchers noted that the results do not imply causality, they emphasized the importance of lowering vascular and heart disease risks. Among the study’s limitations was the possibility that asymptomatic atrial fibrillation or silent strokes may have been missed in some study participants.

Additionally, dementia develops slowly, therefore, some participants with milder symptoms may have been missed, and some patients in the study may have died before dementia was observed and documented. The study may also not be generalizable among populations with different demographics.