Despite indications that TBI may be a precursor for cognitive decline and subsequent development of Alzheimer’s disease (AD), little is known about the time course of this relationship and the factors that contribute to synaptic dysfunction and neurodegeneration. We summarized the current evidence on the course and prognostic factors of cognitive outcome in adults with TBI.  Our results highlighted that as time since injury progresses, performance of measures of recent memory, executive function, language, and information processing speed tend to improve or remain stable from baseline in non-sports-related mild TBI samples and mixed severity samples, indicating potential neurogenesis or practice effect. Severe injury results depict mostly improvements or stability with respect to cognitive performance, and as last follow up time progresses it appears that improvements are abated and reports of no change dominate. Although several mechanisms were found to modulate the risk of cognitive decline in persons with TBI, the evidence in the longitudinal studies published to date suggests the ability of the brain to compensate and naturally recover after injury is associated with genetic makeup, injury severity and count, age, and sex. The evidence taken together, however, is not strong and, as such, not convincing of the presence and strength of a relationship between TBI and cognitive decline, and subsequent risk for development of neurodegenerative disorders. Some of the issues in the studies published to date are attributable to the limited information present on evaluative properties of the outcome measures used to assess cognition, unknown sensitivity to changes over time and practice effect. Future work must apply these considerations in their design process and execution to circumvent issues present in current studies, providing a more concrete understanding of the relationship in question and factors that modulate it.

Evidence Synthesis on Traumatic Brain Injury as a Precursor for Neurodegeneration, Cognitive Decline, and Development of Alzheimer’s Disease