Long‐term low dose nitisinone therapy in adults with alkaptonuria shows no cognitive decline or increased severity of depression

Little is documented on whether nitisinone‐induced hypertyrosinaemia alters cognitive functioning or leads to worsening depression in alkaptonuria (AKU). Wechsler Adult Intelligence Scale‐IV (WAIS‐IV) and Beck Depression Inventory‐II (BDI‐II) assessments were performed before and annually following...

Full description

Saved in:

Bibliographic Details
Published in:	JIMD reports Vol. 63; no. 3; pp. 221 - 230
Main Authors:	Davison, Andrew S., Hughes, Gin, Harrold, Joanne A., Clarke, Pam, Griffin, Rebecca, Ranganath, Lakshminarayan R.
Format:	Journal Article
Language:	English
Published:	Hoboken, USA John Wiley & Sons, Inc 01-05-2022 Wiley
Subjects:	Age Alkaptonuria BDI‐II Cognition & reasoning cognitive functioning Correlation analysis depression Dopamine Intelligence Longitudinal studies Metabolism Metabolites Nervous system nitisinone Research Report Research Reports Software WAIS‐IV United Kingdom > UK United States > US nitisinone WAIS‐IV cognitive functioning depression Alkaptonuria BDI‐II
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Little is documented on whether nitisinone‐induced hypertyrosinaemia alters cognitive functioning or leads to worsening depression in alkaptonuria (AKU). Wechsler Adult Intelligence Scale‐IV (WAIS‐IV) and Beck Depression Inventory‐II (BDI‐II) assessments were performed before and annually following treatment with nitisinone 2 mg daily to assess the impact on cognitive functioning and severity of depression. Serum tyrosine concentrations were also measured annually. WAIS‐IV: 63 patients (27 females/36 males: mean age[years] [±standard deviation, range] 55.7[13.7, 26–79]; 60.3[9.6, 19–75]) were included at baseline for assessment of: verbal comprehension (VC), perceptual reasoning (PR), working memory (WM), and processing speed (PS) using separate indices. Over the 6‐year period studied 43, 39, 36, 29, 26 and 15 patients had annual assessments. Using a longitudinal model (age and sex adjusted) no significant differences were observed in any of the indices over this period, apart from VC which showed a significant increase after adjustment for sex (p < 0.05). BDI‐II: 74 patients (32 females/42 males: mean age[years] [±standard deviation, range] 56.1[13.2, 26–79]; 42 males, 51.5[16.3, 19–70]) were included at baseline. Over the 7‐year period studied 48, 47, 38, 34, 32, 24 and 12 patients had annual assessments. No significant differences in BDI‐II scores were observed when compared to baseline. Hypertyrosinaemia was observed in all patients following treatment with nitisinone (p < 0.001, at all annual visits). Serum tyrosine was not correlated with WAIS‐IV sub‐test indices or BDI‐II scores pre‐ or post‐nitisinone therapy. These findings suggest that treatment with nitisinone does not affect cognitive functioning and or lead to increased severity of depression.
Bibliography:	Funding information Jaak Jaeken This work was funded by the Department of Health‘s NHS Highly Specialised Services Commissioning Group. Andrew S. Davison and Gin Hughes are joint first authors. Communicating Editor ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Communicating Editor: Jaak Jaeken Funding informationThis work was funded by the Department of Health‘s NHS Highly Specialised Services Commissioning Group.
ISSN:	2192-8312 2192-8304 2192-8312
DOI:	10.1002/jmd2.12272