APOEε4 impacts up-regulation of brain-derived neurotrophic factor after a six-month stretch and aerobic exercise intervention in mild cognitively impaired elderly African Americans: A pilot study.

Possession of the Apolipoprotein E (APOE) gene ε4 allele is the most prevalent genetic risk factor for late onset Alzheimer's disease (AD). Recent evidence suggests that APOE genotype differentially affects the expression of brain-derived neurotrophic factor (BDNF). Notably, aerobic exercise-induced upregulation of BDNF is well documented; and exercise has been shown to improve cognitive function. As BDNF is known for its role in neuroplasticity and survival, its upregulation is a proposed mechanism for the neuroprotective effects of physical exercise. In this pilot study designed to analyze exercise-induced BDNF upregulation in an understudied population, we examined the effects of APOEε4 (ε4) carrier status on changes in BDNF expression after a standardized exercise program. African Americans, age 55years and older, diagnosed with mild cognitive impairment participated in a six-month, supervised program of either stretch (control treatment) or aerobic (experimental treatment) exercise. An exercise-induced increase in VO2Max was detected only in male participants. BDNF levels in serum were measured using ELISA. Age, screening MMSE scores and baseline measures of BMI, VO2Max, and BDNF did not differ between ε4 carriers and non-ε4 carriers. A significant association between ε4 status and serum BDNF levels was detected. Non-ε4 carriers showed a significant increase in BDNF levels at the 6month time point while ε4 carriers did not. We believe we have identified a relationship between the ε4 allele and BDNF response to physiologic adaptation which likely impacts the extent of neuroprotective benefit gained from engagement in physical exercise. Replication of our results with inclusion of diverse racial cohorts, and a no-exercise control group will be necessary to determine the scope of this association in the general population.

Development and initial validation of a disease specific outcome measure for early onset scoliosis.

INTRODUCTION: Treatment of children with early onset scoliosis (EOS) seeks to improve natural history and health related quality of life (QOL). QOL measurement presents a significant challenge given the young age, comorbidities, and heterogeneity of this population. OBJECTIVE: To develop a disease specific measure reflecting issues of importance to EOS patients and caretakers. MATERIALS AND METHODS: Review of the literature and relevant measures informed development of semi-structured qualitative interviews. Interviews of caregivers of EOS patients were interpreted through the framework technique. A master-list of 75-items was created and responses were scaled on a 5-point Likert-scale. Psychometric analysis was performed to group items into domains, to maintain score distribution, to create a responsive instrument, and to identify question redundancy. RESULTS: Content validation revealed 8-items with low content validity indices. Item distribution analysis demonstrated 19-items with skewed distribution. Item reliability demonstrated redundant items within domains (r> or =0.5). Construct validity demonstrated unique domains measuring intended issues of interest. The resulting Early Onset Scoliosis Questionnaire (EOSQ) includes 33-items in 13-domains: General Health, Pain, Physical Function, Pulmonary Function, Daily Living, Fatigue, Emotion, Surgical Concerns, Satisfaction, Transfer, Financial Burden, Parental Burden, and Treatment Outcomes. CONCLUSION: The EOSQ reflects QOL and caregiver burden in the EOS population. The EOSQ will expand options for outcome assessment in this unique population.