In the JournalsPerspective

Congenital heart disease increases risk for dementia

People with congenital heart disease who survived to adulthood had an elevated risk for dementia, particularly early-onset dementia, compared with the general population, according to a study published in Circulation.

“Previous studies showed that people born with heart defects have a higher risk of neurodevelopmental problems in childhood such as epilepsy and autism, but this is, to our knowledge, the first study to examine the potential for dementia later in adult life,” Carina N. Bagge, BSc, medical student in the department of clinical epidemiology at Aarhus University Hospital in Denmark, said in a press release.

Researchers analyzed data from 10,632 patients (46% men) with congenital heart disease who were alive at age 30 years. Data from patients who were diagnosed with congenital heart disease between 1963 and 1974 were retrieved from medical records review, and those diagnosed between 1977 and 2012 were from the Danish National Patient Registry.

Each patient with congenital heart disease was matched with 10 patients from the general population based on birth year and sex. Data were from the Civil Registration System.

The primary outcome of interest was first-time hospital diagnosis of all-cause dementia after age 30 years in an inpatient or outpatient setting. The threshold of age 65 years was used to categorize diagnoses by early and late-onset dementia.

People with congenital heart disease who survived to adulthood had an elevated risk for dementia, particularly early-onset dementia, compared with the general population.
Photo credit: Shutter Stock

Patients were followed up until they moved abroad, were diagnosed with dementia, died or when the study ended, whichever came first.

During follow-up, 4% of participants from both cohorts were diagnosed with dementia by age 80 years.

Compared with the general population cohort, the overall HR for dementia in adults with congenital heart disease was 1.61 (95% CI, 1.29-2.02). This did not differ between men (HR = 1.55; 95% CI, 1.06-2.26) and women (HR = 1.65; 95% CI, 1.25-2.19).

Patients with mild to moderate congenital heart disease complexity had an HR of 1.5 (95% CI, 1.14-1.97), whereas the HR in those with severe and univentricular congenital heart disease was 1.96 (95% CI, 1.15-3.34). Those with congenital heart disease who did not have extracardiac defects had an HR of 1.38 (95% CI, 1.08-1.76).

The HR for early-onset dementia was higher (HR = 2.6; 95% CI, 1.8-3.8) compared with late-onset dementia (HR = 1.3; 95% CI, 1-1.8).

“Adults with [congenital heart disease] acquire cardiovascular morbidities earlier than members of the general population, which may impact the brain reserve,” Bagge and colleagues wrote. “These morbidities, which include atrial fibrillation, stroke, diabetes mellitus, coronary artery disease and heart failure, are associated with an enhanced risk of cognitive decline and dementia.” – by Darlene Dobkowski

Disclosures: The authors report no relevant financial disclosures.

People with congenital heart disease who survived to adulthood had an elevated risk for dementia, particularly early-onset dementia, compared with the general population, according to a study published in Circulation.

“Previous studies showed that people born with heart defects have a higher risk of neurodevelopmental problems in childhood such as epilepsy and autism, but this is, to our knowledge, the first study to examine the potential for dementia later in adult life,” Carina N. Bagge, BSc, medical student in the department of clinical epidemiology at Aarhus University Hospital in Denmark, said in a press release.

Researchers analyzed data from 10,632 patients (46% men) with congenital heart disease who were alive at age 30 years. Data from patients who were diagnosed with congenital heart disease between 1963 and 1974 were retrieved from medical records review, and those diagnosed between 1977 and 2012 were from the Danish National Patient Registry.

Each patient with congenital heart disease was matched with 10 patients from the general population based on birth year and sex. Data were from the Civil Registration System.

The primary outcome of interest was first-time hospital diagnosis of all-cause dementia after age 30 years in an inpatient or outpatient setting. The threshold of age 65 years was used to categorize diagnoses by early and late-onset dementia.

People with congenital heart disease who survived to adulthood had an elevated risk for dementia, particularly early-onset dementia, compared with the general population.
Photo credit: Shutter Stock

Patients were followed up until they moved abroad, were diagnosed with dementia, died or when the study ended, whichever came first.

During follow-up, 4% of participants from both cohorts were diagnosed with dementia by age 80 years.

Compared with the general population cohort, the overall HR for dementia in adults with congenital heart disease was 1.61 (95% CI, 1.29-2.02). This did not differ between men (HR = 1.55; 95% CI, 1.06-2.26) and women (HR = 1.65; 95% CI, 1.25-2.19).

Patients with mild to moderate congenital heart disease complexity had an HR of 1.5 (95% CI, 1.14-1.97), whereas the HR in those with severe and univentricular congenital heart disease was 1.96 (95% CI, 1.15-3.34). Those with congenital heart disease who did not have extracardiac defects had an HR of 1.38 (95% CI, 1.08-1.76).

The HR for early-onset dementia was higher (HR = 2.6; 95% CI, 1.8-3.8) compared with late-onset dementia (HR = 1.3; 95% CI, 1-1.8).

“Adults with [congenital heart disease] acquire cardiovascular morbidities earlier than members of the general population, which may impact the brain reserve,” Bagge and colleagues wrote. “These morbidities, which include atrial fibrillation, stroke, diabetes mellitus, coronary artery disease and heart failure, are associated with an enhanced risk of cognitive decline and dementia.” – by Darlene Dobkowski

Disclosures: The authors report no relevant financial disclosures.

    Perspective

    Yuli Y. Kim

    Adult congenital heart disease specialists have long held a notion about their patients — that adults with congenital heart disease are chronologically young people with “old” body parts. Not just a notion anymore, this concept of premature aging in adult congenital heart disease has grown stronger by research demonstrating higher prevalence of acquired adult-onset comorbidities and, of course, increased risk for HF from structural heart disease, all at a relatively younger age (Bouchardy J, et al. Circulation. 2009;doi: 10.1161/CIRCULATIONAHA.109.866319; Billett J, et al. Heart. 2008;doi: 10.1136/hrt.2007.122671).
    Now Bagge and colleagues have added another organ to the mix: the brain. In a population study that could only be performed in a country with universal health care and a robust medical records system, the conclusions are startling. Adults with congenital heart disease are at increased risk for dementia, and particularly early-onset dementia, a diagnosis traditionally reserved for the elderly, but not anymore. The authors rightfully refer to growing attention on neurocognitive outcomes in the young relative to congenital heart disease, but are the first to specifically address dementia later in life. The signal is stronger for those with more complex forms of congenital heart disease, but risk persists even with relatively simple disease such as septal defects.  Even accounting for genetic syndromes such as Trisomy 21 and other acquired comorbidities known to be associated with cognitive impairment such as atrial fibrillation, stroke and CAD, the risk persists.
    The relationship between heart and brain in congenital heart disease is still not fully understood. We have a growing fund of knowledge on neurocognitive outcomes in congenital heart disease and more attention on the brain in this condition but data specifically on dementia is lacking. 
    Awareness is a lot, but we need to know about the etiology. If practitioners are aware that these patients are at risk for cognitive impairment at an earlier age, practitioners may prescribe early screening, referral for neurocognitive testing. Treatments that could potentially decrease this risk depending on the etiology (ie, exercise prescription) could be explored. It is still too early for this research to impact day-to-day clinical practice right now.
    There is a growing body of research on neurocognitive outcomes in the young, so more in the older adult is warranted. These results are derived from a population study, which is highly reliant on accurate coding, so they need to be validated. We don’t have a great grasp on the impact of aging on end-organ damage such as dementia in adults with congenital heart disease or the impact of effects of other risk factors for dementia (ie, hypertension, congestive HF, stroke) that we see in adults with congenital heart disease.
    The conclusions merit further study, but like any good research, lead to a number of provocative new questions. Are there risk factors in infancy, childhood or even in utero that could be addressed to mitigate risk of dementia later in life? Would therapies for adult-onset comorbidities such as exercise training or statins be effective in preventing dementia? Adding to attention on the brain in congenital heart disease (Marelli A, et al. Circulation. 2016;doi:10.1161/CIRCULATIONAHA.115.019881.), this piece of research reframes the concept of senescence in congenital heart disease as these patients continue to survive and thrive well into adulthood.

    • Yuli Y. Kim, MD
    • Cardiology Today Next Gen Innovator
      Assistant Professor
      The Hospital of the University of Pennsylvania
      The Children’s Hospital of Philadelphia

    Disclosures: Kim reports no relevant financial disclosures.