Older age and higher severity of peripheral polyneuropathy are potential predictors of cognitive dysfunction in patients with hereditary transthyretin amyloidosis (hATTR) harboring the TTR V30M variant who had undergone liver transplant, according to a new study published in Amyloid.

“In comparison to normal cognition, both mild and moderate cognitive dysfunction patients had older age, higher mPND [modified polyneuropathy disability] score and elevated NT-proBNP [N-terminal pro-brain natriuretic peptide] and cystatin C values,” the authors wrote.

Patients with cognitive dysfunction had a median age of 50 years, whereas patients with normal cognition had a median age of 45 years. The median modified polyneuropathy disability score was 2 and 1 in patients with and without cognitive dysfunction, respectively. Elevated N-terminal pro-brain natriuretic peptide (ie, ≥227) and cystatin C (ie, ≥1.11) values were found in 84% and 71% of patients with cognitive dysfunction, respectively, compared with 40% and 34% of patients with normal cognition.

Moreover, patients with cognitive dysfunction also had fewer years of education (6 vs 8 years), longer disease duration (17 vs 14 years) and post-liver transplant duration (13 vs 10 years), and more focal neurological episodes (46% vs 28%) and cognitive complaints (42% vs 18%) than patients with normal cognition.

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Further analysis of cognitive dysfunction subgroups showed that patients with mild dysfunction had longer disease duration (21 vs 15 years) and post-liver transplant duration (17 vs 10 years) than those with moderate dysfunction.

The comparison between cognitive dysfunction and normal cognition groups did not reveal any statistically significant difference in sex, age at disease onset, presence of atrial flutter or atrial fibrillation, or frequencies of anxiety and depression as evaluated through the Hospital Anxiety and Depression Scale.

The study enrolled 269 individuals (median age, 45 years old, 55% male) with hATTR-V30M treated with liver transplant at Centro Hospitalar Universitário do Porto in Portugal. Of those, 87% had normal cognition, while the remaining had mild or moderate cognitive dysfunction (5% and 8%, respectively).


Cavaco S, Martins da Silva A, Fernandes J, et al. Predictors of cognitive dysfunction in hereditary transthyretin amyloidosis with liver transplant. Amyloid. Published online October 17, 2022. doi:10.1080/13506129.2022.2131384