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Thomas V Fungwe,1 Julius S Ngwa,2 Oyonumo E Ntekim,1 Joanne S Allard,3 Sheeba Nadarajah,4 Saba Wolday,5 Oludolapo O Ogunlana,5 Steven P Johnson,5 Kakra Hughes,6 Daniel Larbi,5 Richard F Gillum,7 Thomas O Obisesan5 1Department of Nutritional Sciences, School of Nursing and Allied Health Sciences, Howard University, Washington, DC, USA; 2Division of Cardiology, Department of Medicine, Howard University, Washington, DC, USA; 3Division of Cardiology, Department of Physiology and Biophysics, Howard University, Washington, DC, USA; 4Division of Nursing, College of Nursing and Allied Health Sciences, Howard University, Washington, DC, USA; 5Division of Geriatrics, Department of Medicine and Clinical, Howard University Hospital, Washington, DC, USA; 6Department of Surgery, Howard University College of Medicine, Washington, DC, USA; 7Department of Internal Medicine, Howard University Hospital, Washington, DC, USACorrespondence: Thomas O ObisesanDivision of Geriatrics, Department of Medicine and Clinical/Translational Science Program, Howard University Hospital, 2041 Georgia Ave NW, Washington, DC 20060, USATel +1 202 865 3397Fax +1 202 865 3777Email tobisesan@howard.eduPurpose: Poor cardiorespiratory fitness (CRF) is linked to cognitive deterioration, but its effects on lipid heterogeneity and functional properties in older African American (AA) subjects with mild cognitive impairment (MCI) need elucidation. This study determined whether exercise training-induced changes in blood lipid particle sizes (LPS) were associated with CRF determined by VO2Max in elderly AAs with MCI. Given the pivotal role of brain-derived neurotrophic factor (BDNF) on glucose metabolism, and therefore, “diabetic dyslipidemia”, we also determined whether changes in LPS were associated with the levels of serum BDNF.Methods: This analysis included 17 of the 29 randomized elderly AAs with MCI who had NMR data at baseline and after a 6-month training. We used Generalized Linear Regression (GLM) models to examine cardiorespiratory fitness (VO2Max) effects on training-induced change in LPS in the stretch and aerobic groups. Additionally, we determined whether the level of BDNF influenced change in LPS.Results: Collectively, mean VO2Max (23.81±6.17) did not differ significantly between aerobic and stretch groups (difference=3.17±3.56, P=0.495). Training-related changes in very low-density lipoprotein, chylomicrons, and total low-density lipoprotein (LDL) particle sizes correlated significantly with VO2Max, but not after adjustment for age and gender. However, increased VO2Max significantly associated with reduced total LDL particle size after similar adjustments (P = 0.046). While stretch exercise associated with increased protective large high-density lipoprotein particle size, the overall effect was not sustained following adjustments for gender and age. However, changes in serum BDNF were associated with changes in triglyceride and cholesterol transport particle sizes (P < 0.051).Conclusion: Promotion of stretch and aerobic exercise to increase CRF in elderly AA volunteers with MCI may also promote beneficial changes in lipoprotein particle profile. Because high BDNF concentration may reduce CVD risk, training-related improvements in BDNF levels are likely advantageous. Large randomized studies are needed to confirm our observations and to further elucidate the role for exercise therapy in reducing CVD risk in elderly AAs with MCI.Keywords: lipoprotein, elderly, exercise, cardiovascular disease, Alzheimer’s disease, brain-derived neurotrophic factor, cardiovascular fitness