Treatment of Dementia with Bosutinib
Abstract: Thirty-one patients with probable Alzheimer's dementia or Parkinson's spectrum disorder with dementia completed 12 months of bosutinib therapy and an additional 12-months of follow-up. The Clinical Dementia Rating scale (as estimated by the Quick Dementia Rating System [QDRS]) was the primary cognitive status outcome measure. Secondary outcome measures included the Repeatable Battery Assessment of Neuropsychological Status (RBANS) and the Montreal Cognitive Assessment. Cox regression methods were used to compare results with population-based estimates of cognitive decline. The present paper reports on cognitive outcomes obtained at 12 months for 31 participants and up to 24 months for a 16-participant subset. Safety and tolerability of bosutinib were confirmed among the study population (Mage = 73.7 years, SDage = 14 years). Bosutinib was associated with less worsening in Clinical Dementia Rating (CDR) scores (HR = −0.62, p < 0.001, 95% confidence interval [CI]: −1.02 to −0.30) and less decline in RBANS performance (HR = −3.42, p < 0.001, 95% CI: −3.59 to −3.72) during the year of treatment than population-based estimates of decline. In the 24-month follow up, wherein 16 patients were observed after 1 year post-intervention, 31.2% of participants exhibited worsened CDR levels compared to their 12-month performances. Results support an overall positive outcome after 1 year of bosutinib. Future studies should explore the relationship between tyrosine kinases and neurodegenerative pathology as well as related avenues of treatment.