Cognitive Impairment Common Among Older, Untreated FAP Patients

Researchers have found that a large proportion of untreated people with the TTRVal30Met mutation — causing familial amyloid polyneuropathy (FAP) — have cognitive impairment, particularly if they experience disease symptoms.

Such problems are more common in older patients and those with late-onset disease, the study, published in the Journal of Neurology showed.

The study, “Age‑dependent cognitive dysfunction in untreated hereditary transthyretin amyloidosis,” demonstrated that cognitive issues are part of the many disease manifestations of FAP.

While some research exists into the impact on brain function in treated patients with FAP — also called hereditary transthyretin (TTR) amyloidosis — there is no research examining if untreated people with the TTRVal30Met mutation have cognitive issues.

Researchers at the Hospital de Santo António in Portugal recruited 340 carriers of the TTRVal30Met mutation, of which 180 had FAP symptoms. Study participants went through a range of cognitive tests and also were screened for depression and anxiety.

None of the study participants had received treatment previously.

Taking age and depression into account, symptomatic mutation carriers were four times more likely to be cognitively impaired compared to people with no disease symptoms.

It was, however, apparent that the problems appeared to be confined to the older population.

Analyses showed that 36 percent of symptomatic mutation carriers, aged 50 or older, had cognitive problems, compared to only 2 percent among symptomatic people under the age of 50. Older patients also more commonly had depression and anxiety than younger patients.

Having cognitive problems was linked to kidney disease, but not eye or heart problems, researchers said.

The study also revealed that people who started experiencing disease symptoms after the age of 50 were more likely to have cognitive problems, also when potentially contributing factors such as education, disease duration, symptom severity, and depression were considered.

Only three of the early onset patients were older than 50 years at the time of the cognitive assessment. Although the small number does not allow for a robust analysis, researchers noted that none of the three patients were cognitively impaired.

While the team argued that the cognitive impairment is likely caused by amyloid aggregation in the brain, they admitted that the study lacked backup by imaging or other biochemical measures supporting this idea.

Nevertheless, more research is needed to assess how TTR amyloid deposits contribute to cognitive impairment in people carrying TTRVal30Met mutations, they said.