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Long‐term low dose nitisinone therapy in adults with alkaptonuria shows no cognitive decline or increased severity of depression
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Long‐term low dose nitisinone therapy in adults with alkaptonuria shows no cognitive decline or increased severity of depression
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Journal Article
Long‐term low dose nitisinone therapy in adults with alkaptonuria shows no cognitive decline or increased severity of depression
2022
Overview
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.
Publisher
John Wiley & Sons, Inc,Wiley
Subject
