A study published in Journal of Neuropsychiatry and Clinical Neuroscience observed the efficacy of donepezil for addressing persistent verbal memory impairments among individuals with predominantly severe traumatic brain injury (TBI) in the chronic post-injury phase provides significant insights into cognitive rehabilitation. The study effectively demonstrated that donepezil yields measurable improvements in persistent verbal memory (learning), supported by a medium effect size.
Donepezil demonstrated additional benefits in managing neuropsychiatric symptoms, particularly anxiety and disinhibition. These improvements likely reflect the augmentation of medial prefrontal and orbitofrontal cortex-mediated anxiety regulation and lateral orbitofrontal cortex-mediated social cognition regulation.
In terms of clinical significance, the study reported that treatment response rates for donepezil were 2.3 times greater than those for placebo, yielding a favorable number needed to treat (NNT) of 3.49. Responders exhibited significant improvements in new learning, delayed recall, and processing speed, with large effect sizes. Medium to large effect sizes were also observed in memory recognition, retention, attention, executive control of attention, and executive function, though these effects could not be definitively tested due to sample size limitations. These results are consistent with prior autopsy studies demonstrating partial losses of basal forebrain cholinergic neurons and their projections in roughly 50% of individuals with TBI.
Despite the positive neuropsychological outcomes, the study did not find significant effects of donepezil on everyday memory function, participation, satisfaction with life, or caregiver observations of memory function. This result may be attributed to the chronic nature of post-traumatic memory impairments (median duration of 3–4 years post-injury), the stability of baseline everyday memory deficits, and the multifactorial nature of societal participation and quality of life. A treatment duration of 10 weeks may be insufficient to translate neuropsychological improvements into tangible benefits in daily functioning and overall life satisfaction.
While the findings are promising, they highlight the need for further research to optimize treatment protocols, identify responders, and integrate pharmacological interventions with cognitive rehabilitation programs to maximize functional and quality-of-life outcomes in patients that suffer from a traumatic brain injury.
Sources: Journal of Neuropsychiatry and Clinical Neuroscience