Dementia Risk Higher in Congenital Heart Disease Survivors

Patrice Wendling

February 12, 2018

A nationwide Danish study suggests the risk for dementia is about 60% higher in adult survivors of congenital heart disease (CHD) than in the general population.[1]

Further, risk was 160%, or 2.6 times, higher for early-onset dementia before age 65 years (hazard ratio [HR], 2.59; 95% CI, 1.76–3.81).

"The take-home message that certainly resonates most for us as clinicians is that congenital heart disease is a lifelong condition," senior author, Dr Nicolas Madsen, from Cincinnati Children's Hospital Medical Center, Ohio, told | Medscape Cardiology.

"We understand that neurodevelopmental disease is an important element in caring for a child with congenital heart disease. This study helps us identify that this is not an area we should limit to the pediatric age group, but rather we should think about these neurodevelopmental, these noncardiac morbidities, extending well into adulthood."

The study was published online February 12 in Circulation.

Madsen and colleagues recently showed that adults with CHD have a more than threefold higher long-term risk for epilepsy than the general public, but this is the first study, he said, to identify a heightened risk for dementia in adults with CHD.

"To me, Nicolas's seizure paper and Nicolas's dementia paper are basically canaries in the coal mine," Dr Bradley Marino, from Lurie Children's Hospital, Chicago, Illinois, said in an interview.

Marino, who coauthored the epilepsy paper but was not involved in the present study, noted that CHD is the most common birth defect and highest cause of infant death. Infants born with CHD have less mature brains, two thirds leave the hospital after heart surgery with a white matter injury and/or stroke, and this brain dysmaturation leads to altered brain development in infancy and early childhood.

Still, 60% of the 2.4 million Americans living with CHD are adults, and "only a handful of papers, and I mean literally a handful of papers, have examined neurocognitive issues in adulthood," he said.

Although more than 30 cardiac neurodevelopmental programs have developed nationally over the last decade, making it hard to be in a major cardiovascular program and not have an onsite neurodevelopmental program, "None of that exists for our adult congenital patients," Marino said.

"Is this on people's radar? The answer is, it's not, but it should be."

Details From Denmark

For the present study, the investigators used two nationwide Danish registries and medical records to identify 10,632 adults (46% male) born with CHD from 1890 to 1982, with 62% born between 1960 and 1982. Each patient was matched for sex and birth year to 10 members of the general population in the Civil Registry System.

The most common CHD diagnoses were atrial septal defects in 26%, ventricular septal defects in 22%, and patent ductus arteriosus in 8%; 65% had mild to moderately complex CHD. Extra cardiac defects were present in 14% of adults with CHD vs 4% of controls.

During follow-up, dementia was diagnosed in 95 adults with CHD (incidence rate, 0.78/1000 person-years) and 977 controls (0.75/1000 person-years).

The HR for dementia overall was 1.61 (95% CI, 1.29–2.02), with an HR of 2.6 for early-onset dementia and 1.3 for late-onset.

Despite the vascular insults in early life, risk was similar for Alzheimer's disease (HR, 1.35; 95% CI, 0.86–2.15), vascular dementia (HR, 1.62; 95% CI, 0.84–3.11), and other dementias (HR, 1.73; 95% CI, 1.30–2.30).

"Our hypothesis was that vascular dementia would be the one with the highest risk, but our results did not show any difference," first author, Carina Bagge, BSc, a medical student at Aarhus University Hospital, Denmark, said in an interview. "But if you look at the confidence intervals, they are a bit wide. So I wouldn't conclude too strongly on these dementia subtypes, but it's definitely surprising."

That said, Madsen noted that the next level of investigation is looking at subtypes of dementia, "in particular trying to identify whether vascular forms of dementia are the ones that are particular to this population."

The risk for dementia was elevated across the entire spectrum of CHD, including mild to moderately complex CHD (HR, 1.50; 95% CI, 1.14–1.97), potential cyanotic lesions (HR, 1.83; 95% CI, 0.69–4.87), acyanotic lesions (HR, 1.42; 95% CI, 1.08–1.89), and especially severe and univentricular disease (HR, 1.96; 95% CI, 1.15–3.34).

Only 62 patients in the study were survivors of single-ventricle disease, and the HRs are likely underestimates because these patients have "a lot more operations, a lot more morbidity in the intensive care unit in terms of air emboli and thromboembolic phenomenon," Marino observed.

Finally, CHD adults with and without additional acquired cardiovascular disease or diabetes were at greater risk for dementia (HR, 1.48 [95% CI, 1.11–1.97] and 1.82 [95% CI, 1.26–2.64]).

"Certainly if you have congenital heart disease and you have some traditional risk factors for dementia, such as congestive heart failure or atrial fibrillation, then the risk does appear to be heightened, but I think the important finding is that even if you don't have those risk factors your risk for dementia remains heightened," Madsen said. "The key just being that congenital heart disease by itself is a unique risk factor that extends beyond what we experience in the general public."

Limitations of the study are the dramatic changes in CHD diagnosis and management over the long study period, lack of dementia awareness in the early study years, and the possibility that this is a healthier population of adult CHD (ACHD) survivors, the authors note.

While life expectancy today should be near normal in patients with, for example, a ventricular septal defect, those with hypoplastic left heart syndrome would be unlikely to have survived because clinicians have started having success with these operations only since the 1980s and 1990s, Madsen said.

Where to Now?

"We wouldn't advocate for screening at this time, but we certainly would advocate for increased investigation," Madsen said.

The Pediatric Heart Network (PHN) is aware that this is a huge gap in knowledge and is starting multicenter projects obtaining specific neurocognitive, psychosocial data in ACHD patients to close that gap, Marino said.

"When we actually see the data come out from the PHN in 3 to 5 years or whatever it is, I think that's going to dramatically change how we think of our ACHD patients in terms of what their specific neurocognitive and/or psychosocial needs are and how we need to treat them," he said.

In the meantime, both men said the study speaks to the need for closer monitoring of adolescents with CHD as they age into adulthood.

"We see a lot of children who, after their parents stop taking them to the cardiologist when they're 18, they're sort of lost to follow-up and there's a tremendous vulnerability in that population," Madsen said. "So I think what this reinforces is the importance within this population of staying connected to your subspecialist."

Marino remarked, "There's a huge gap right now relative to surveillance, screening, evaluation, and treatment in adults who have known neurodevelopmental issues as children and have become adults. That's lacking, but more importantly there's no way to pay for these services."

Dr Gary Webb, editor-in-chief for the Congenital Heart Professionals Network and the Adult Congenital Heart Disease Learning Center, said the results would likely have been different in a more contemporary cohort but still serve as a wake-up call.

In children, "We should be doing a better job of treating their brains as well as their hearts. I think that as a general rule we do a poor job of that," he said.

"In the adult world, we argue about how common psychological problems are in these patients" but "when it comes down to social workers or psychologists, this is seldom seen as a priority by institutions."

The study was funded by the Aarhus University Hospital, the Heart Institute at Cincinnati Children's Hospital, the National Institute on Aging, the Foundation of the Family Kjaersgaard Sunds, the Foundation of 1870, the Foundation of Raimond and Dagmar Ringgaard-Bohn, the Foundation of Torben and Alice Frimodt, the Foundation of the Family Hede-Nielsen, and the Oticon Foundation. The investigators, Marino, and Webb report no financial relationships.

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