Abstract
• Cognitive impairment is a common consequence of traumatic brain injury (TBI) and a substantial source of disability. Across all levels of TBI severity, attention, processing speed, episodic memory, and executive function are most commonly affected.• The differential diagnosis for post-traumatic cognitive impairments is broad, and includes emotional, behavioral, and physical problems as well as substance use disorders, medical conditions, prescribed and self-administered medications, and symptom elaboration. Thorough neuropsychiatric assessment for such problems is a prerequisite to treatments specifically targeting cognitive impairments.• First-line treatments for post-traumatic cognitive impairments are nonpharmacologic, including education, realistic expectation setting, environmental and lifestyle modifications, and cognitive rehabilitation.• Pharmacotherapies for post-traumatic cognitive impairments include uncompetitive N-methyl-D-aspartate receptor (NMDA) antagonists, medications that directly or indirectly augment cerebral catecholaminergic or acetylcholinergic function, or agents with combinations of these properties.• In the immediate post-injury period, treatment with uncompetitive NMDA receptor antagonists reduces duration of unconsciousness. The mechanism for this effect may involve attenuation of neurotrauma-induced glutamate-mediated excitotoxicity and/or stabilization of glutamate signaling in the injured brain.• During the subacute or late post-injury periods, medications that augment cerebral acetylcholinergic function may improve declarative memory. Among responders to this treatment, secondary benefits on attention, processing speed, and executive function impairments as well as neuropsychiatric disturbances may be observed. During these post-injury periods, medications that augment cerebral catecholaminergic function may improve hypoarousal, processing speed, attention, and/or executive function as well as comorbid depression or apathy.• When medications are used, a "start-low, go-slow, but go" approach is encouraged, coupled with frequent reassessment of benefits and side effects as well as monitoring for drug-drug interactions. Titration to either beneficial effect or medication intolerance should be completed before discontinuing a treatment or augmenting partial responses with additional medications.