APOE×BDNF Interaction and Poorer Cognitive Outcomes Among Veterans With Mild Traumatic Brain Injury: An Exploratory Study.

OBJECTIVE: The authors examined the interaction between apolipoprotein E (APOE) ε4 and brain-derived neurotrophic factor (BDNF) Val66Met alleles on neuropsychological functioning among veterans with histories of mild traumatic brain injury (mTBI). METHODS: Participants were 78 veterans with mTBI (85% males; mean±SD age=32.95±7.00 years; mean time since injury=67.97±34.98 months) who completed a structured clinical interview and underwent a comprehensive neuropsychological assessment. Participants also provided a buccal swab for determination of their APOE and BDNF genotypes. Three cognitive composite scores were calculated from the neuropsychological assessment, reflecting visuospatial speed (seven variables), executive functioning (10 variables), and memory (eight variables). Two-way analyses of covariance (ANCOVAs) adjusted for age, sex, and race-ethnicity were used to assess the effects of APOE (ε4+ vs. ε4-) and BDNF (Met+ vs. Met-) on cognitive functioning. RESULTS: ANCOVAs revealed no significant main effects of APOE or BDNF genotypes on cognitive functioning; however, there was a significant APOE-by-BDNF genotype interaction for all three cognitive composite measures (visuospatial speed: ηp2=0.055; executive functioning: ηp2=0.064; and memory: ηp2=0.068). Specifically, the ε4+/Met+ (N=8) subgroup demonstrated the poorest cognitive functioning relative to all other allele subgroups (ε4+/Met-: N=12, ε4-/Met+: N=23, and ε4-/Met-: N=35). CONCLUSIONS: This exploratory study is the first to show that, compared with other allele subgroups assessed, veterans with both ε4 and Met alleles demonstrated the poorest cognitive functioning across several cognitive domains known to be negatively affected in the context of mTBI. Further research with larger sample sizes is needed to replicate these findings.

Prospective memory performance in veterans with and without histories of mild traumatic brain injury: effect of the apolipoprotein E (APOE) ε4 genotype.

OBJECTIVE: Identifying factors that moderate cognitive outcomes following mild traumatic brain injury (mTBI) is crucial. Prospective memory (PM) is a cognitive domain of interest in mTBI recovery as it may be especially sensitive to TBI-related changes. Since studies show that genetic status - particularly possession of the apolipoprotein E (APOE) ε4 allele - can modify PM performance, we investigated associations between mTBI status and APOE-ε4 genotype on PM performance in a well-characterized sample of Veterans with neurotrauma histories. METHODS: 59 Veterans (mTBI = 33, Military Controls [MCs] = 26; age range: 24-50; average years post-injury = 10.41) underwent a structured clinical interview, neuropsychological assessment, and genotyping. The Memory for Intentions Test (MIST) measured PM across multiple subscales. ANCOVAs, adjusting for age and posttraumatic stress symptoms, tested the effects of mTBI status (mTBI vs. MC) and ε4 status (ε4+ vs. ε4-) on MIST scores. RESULTS: Veterans with mTBI history performed more poorly compared to MCs on the MIST 15-min delay (p=.002, ηp2 =.160), Time Cue (p = .003, ηp2 =.157), and PM Total (p = .016, ηp2 =.102). Those with at least one copy of the ε4 allele performed more poorly compared to ε4- Veterans on the MIST 15-min delay (p = .011, ηp2 =.113) and PM Total (p = .048, ηp2 = .071). No significant interactions were observed between mTBI and APOE-ε4 status on MIST outcomes (ps>.25). Within the mTBI group, APOE-ε4+ Veterans performed worse than APOE-ε4- Veterans on the MIST 15-min delay subscale (p = .031, ηp2 = .150). CONCLUSIONS: mTBI history and APOE-ε4 genotype status were independently associated with worse PM performance compared to those without head injury histories or possession of the APOE-e4 genotype. Performance on the MIST 15-min delay was worse in Veterans with both risk factors (mTBI history and APOE-ε4 positivity). Findings suggest that genetic status may modify outcomes even in relatively young Veterans with mTBI histories. Future research examining longitudinal associations and links to neuroimaging and biomarker data are needed.

Prevalence of and Risk Factors for Post-traumatic Headache in Civilian Patients After Mild Traumatic Brain Injury: A TRACK-TBI Study.

OBJECTIVE: To ascertain the prevalence of and risk factors for post-traumatic headache (PTH) attributed to mild traumatic brain injury (mTBI). PATIENTS AND METHODS: A prospective, longitudinal, multicenter cohort study of patients with mTBI and orthopedic trauma controls who were enrolled from February 26, 2014, to August 8, 2018. The baseline assessment was conducted as soon as possible following evaluation at the emergency department. Follow-ups were scheduled at 2 weeks, 3 months, 6 months, and 12 months postinjury. Eligible patients with mTBI included those 18 years of age or older who presented to the emergency department within 24 hours of head injury warranting evaluation by noncontrast head computed tomography scan. Acute PTH was considered present when a patient reported a headache score of greater than or equal to 2 on the Rivermead Post-concussion Questionnaire at 2 weeks postinjury (ie, headache is at least a mild problem compared with pre-injury). Persistent PTH was defined when a patient with acute PTH reported a Rivermead Post-concussion Questionnaire headache score of greater than or equal to 2 at the scheduled follow-up examinations. RESULTS: Acute PTH was reported by 963 (60.4%) of 1594 patients with mTBI at 2 weeks postinjury. Among those with acute PTH, 439 (52.4%) of 837 patients reported persistent PTH at 3 months postinjury. This figure decreased over time and 278 (37.5%) of 742 patients continued to report persistent PTH at 6 months, whereas 187 (28.9%) of 646 patients did so as well at 12 months postinjury. Risk factors for acute PTH included younger age, female sex, fewer years of formal education, computed tomography-positive scans, alteration of consciousness, psychiatric history, and history of migraine. Risk factors for persistent PTH included female sex, fewer years of formal education, and history of migraine. CONCLUSION: Post-traumatic headache is a prevalent sequela of mTBI that persists for at least 12 months in a considerable proportion of affected individuals. The attributable burden necessitates better patient follow-up, disease characterization, improved awareness of PTH in clinical practice, and identification of effective therapies.

King-Devick Test identifies real-time concussion and asymptomatic concussion in youth athletes.

BACKGROUND: Sports concussion has an annual incidence of approximately 3.8 million. Over half go unreported and a substantial number may be asymptomatic. A rapid, cost-effective, and reliable tool that facilitates diagnosis of concussion is needed. The King-Devick (K-D) test is a vision-based tool of rapid number naming for assessment of concussion. In this study, we evaluated the utility of the K-D test in real time for identification of symptomatic concussion in youth athletes and to determine if similar impairment (subclinical concussion) exists in youth athletes without an obvious head injury or symptoms. METHODS: Youth hockey players underwent K-D testing preseason, postseason, and immediately after suspected concussion. Additional testing was performed in a subgroup of nonconcussed athletes immediately before and after a game to determine effects of fatigue on K-D scores. RESULTS: Among 141 players tested, 20 had clinically diagnosed concussion. All 20 had immediate postconcussion K-D times >5 seconds from baseline (average 7.3 seconds) and all but 2 had worse postseason scores (46.4 seconds vs 52.4 seconds, p < 0.05, Wilcoxon signed rank test). Nonconcussed athletes saw minimal improvement postseason (43.9 seconds vs 42.1 seconds, p < 0.05) and 51 nonconcussed players assessed before and after a game revealed no significant time change as a result of fatigue. CONCLUSIONS: Rapid number naming using the K-D test accurately identifies real-time, symptomatic concussion in youth athletes. Scores in concussed players may remain abnormal over time. Athletes should undergo preseason and postseason K-D testing, with additional evaluation real time to inform the assessment of suspected concussion. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that the K-D test accurately identifies real-time concussions in youth athletes.

Abnormal visual contrast acuity in Parkinson's disease.

BACKGROUND: Low-contrast vision is thought to be reduced in Parkinson's disease (PD). This may have a direct impact on quality of life such as driving, using tools, finding objects, and mobility in low-light condition. Low-contrast letter acuity testing has been successful in assessing low-contrast vision in multiple sclerosis. We report the use of a new iPad application to measure low-contrast acuity in patients with PD. OBJECTIVE: To evaluate low- and high-contrast letter acuity in PD patients and controls using a variable contrast acuity eye chart developed for the Apple iPad. METHODS: Thirty-two PD and 71 control subjects were studied. Subjects viewed the Variable Contrast Acuity Chart on an iPad with both eyes open at two distances (40 cm and 2 m) and at high contrast (black and white visual acuity) and 2.5% low contrast. Acuity scores for the two groups were compared. RESULTS: PD patients had significantly lower scores (indicating worse vision) for 2.5% low contrast at both distances and for high contrast at 2 m (p < 0.003) compared to controls. No significant difference was found between the two groups for high contrast at 40 cm (p = 0.12). CONCLUSIONS: Parkinson's disease patients have reduced low and high contrast acuity compared to controls. An iPad app, as used in this study, could serve as a quick screening tool to complement more formal testing of patients with PD and other neurologic disorders.