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Abstract Objectives Traumatic brain injury (TBI) is associated with sleep deficits, but it is not clear why some report sleep disturbances and others do not. The objective of this study was to assess the associations between axonal injury, sleep, and memory in chronic and acute TBI. Methods Data were acquired from two independent datasets which included 156 older adult veterans (69.8 years) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) with prior moderate‐to‐severe TBIs and 90 (69.2 years) controls and 374 (39.6 years) from Transforming Research and Clinical Knowledge in TBI (TRACK‐TBI) with a recent mild TBI (mTBI) and 87 controls (39.6 years), all who completed an MRI, memory assessment, and sleep questionnaire. Results Older adults with a prior TBI had a significant association between axonal injury and sleep disturbances [β = 9.52, 95% CI (4.1, 14.9), p = 0.01]. Axonal injury predicted changes in memory over 1‐year in TBI [β = −8.72, 95% CI (−18, −2.7), p = 0.03]. We externally validated those findings in TRACK‐TBI where axonal injury within 2 weeks after mTBI was significantly associated with higher sleep disturbances in the TBI group at 2 weeks[β = −7.2, 95% CI (−14, −0.50), p = 0.04], 6 months [β = −16, 95% CI (−24, −7.6), p ≤ 0.01], and 12 months post‐injury [β = −11, 95% CI (−19, −0.85), p = 0.03]. These associations were not significant in controls. Interpretations Axonal injury, specifically to the left anterior internal capsule is robustly associated with sleep disturbances in multiple TBI populations. Early assessment of axonal injury following mTBI could identify those at risk for persistent sleep disturbances following injury.

Abstract Background Prolonged changes to functional network connectivity as a result of a traumatic brain injury (TBI) may relate to long‐term cognitive complaints reported by TBI survivors. No interventions have proven to be effective at treating long‐term cognitive complaints after TBI but physical activity has been shown to promote cognitive function and modulate functional network connectivity in non‐injured adults. Therefore, the objective of this study was to test if physical activity engagement was associated with functional connectivity of the cognitively relevant frontoparietal control network (FPCN) in adults with a TBI history. Methods In a case‐control study design, resting state function magnetic resonance imaging and physical activity data from a subset of participants (18–81 years old) from the Cambridge Centre for Ageing and Neuroscience (Cam‐CAN) study was analyzed. Fifty‐seven participants reported a prior head injury with loss of consciousness and 57 age and sex matched controls were selected. Seed‐based functional connectivity analyses were performed using seeds in the dorsolateral prefrontal cortex and the inferior parietal lobule, to test for differences in functional connectivity between groups, associations between physical activity and functional connectivity within TBI as well as differential associations between physical activity and functional connectivity between TBI and controls. Results Seed‐based connectivity analyses from the dorsolateral prefrontal cortex showed that those with a history of TBI had decreased positive connectivity between dorsolateral prefrontal cortex and intracalcarine cortex, lingual gyrus, and cerebellum, and increased positive connectivity between dorsolateral prefrontal cortex and cingulate gyrus and frontal pole in the TBI group. Results showed that higher physical activity was positively associated with increased connectivity between the dorsolateral prefrontal cortex and inferior temporal gyrus. Differential associations were observed between groups whereby the strength of the physical activity‐functional connectivity association was different between the inferior parietal lobule and inferior temporal gyrus in TBI compared to controls. Discussion Individuals with a history of TBI show functional connectivity alterations of the FPCN. Moreover, engagement in physical activity is associated with functional network connectivity of the FPCN in those with a TBI. These findings are consistent with the evidence that physical activity affects FPCN connectivity in non‐injured adults; however, this effect presents differently in those with a history of TBI.

Background Evidence in older adults suggests that higher cardiorespiratory fitness and lower cardiovascular risk are associated with greater cognition. However, given that changes in the brain that lead to cognitive decline begin decades before the onset of symptoms, understanding the mechanisms by which modifiable cardiovascular factors are associated with brain health in midlife is critical and can lead to the development of strategies to promote and maintain brain health as we age. Methods and Results In 501 middle‐aged (aged 40–65 years) adult participants of the BBHI (Barcelona Brain Health Initiative), we found differential associations among cardiorespiratory fitness, cardiovascular risk, and cognition and cortical thickness. Higher cardiorespiratory fitness was significantly associated with better visuospatial abilities and frontal loading abstract problem solving (β=3.16, P=0.049) in the older middle‐aged group (aged 55–65 years). In contrast, cardiovascular risk was negatively associated with better visuospatial reasoning and problem‐solving abilities (β=−0.046, P=0.002), flexibility (β=−0.054, P