Cerebral Microvascular Pathology Is a Common Endophenotype Between Traumatic Brain Injury, Cardiovascular Disease, and Dementia: A Hypothesis and Review

Traumatic brain injury (TBI) exposure has been associated with an increased risk of age-related cognitive decline or dementia in multiple epidemiological studies. Current therapeutic interventions in the field of Brain Injury Medicine focus largely on episodic symptom management during the chronic phase of TBI recovery, rather than targeting specific underlying pathological processes. This approach may be especially problematic for secondary age-related cognitive decline or dementia following TBI exposure. Although there are likely multiple pathophysiological mechanisms involved, a growing body of literature demonstrates that cerebral microvascular pathology is a common endophenotype across the spectrum of TBI severity. Similarly, a combination of pre-clinical and clinical research over the past two decades has implicated cerebral microvascular pathology in the initiation and progression of multiple neurodegenerative diseases, including Alzheimer’s disease and other dementias. We hypothesize that cerebral microvascular pathology is a common endophenotype between TBI, cardiovascular disease (CVD), and dementia, which can be targeted through modifiable cardiovascular risk factor reductions during the chronic phase of TBI recovery. We posit that our hypothesis is supported by the currently available scientific literature, as detailed in our review.