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Adults with traumatic brain injury (TBI) are often severely impaired and inadequately rehabilitated due to deficits in memory and behavioral problems like apathy, irritability and depression, and it has been suggested that an acetylcholine deficit could be contributory to these deficits. Central Acetyl cholinesterase Inhibitors (CAI) are being reported to have a beneficial impact in treatment of memory deficits in adults with TBI, with Donepezil studied most extensively. The authors present two patients with TBI with long term static dysfunction of memory and behavior who responded to Donepezil in terms of attention, memory and apathy. Donepezil appears to be a valuable pharmacological option for treatment of memory and behavioral deficits in TBI.