Victoria Sanborn1, Sarah R Preis2,3, Alvin Ang2, Sherral Devine2,4, Jesse Mez2,4,5, Charles DeCarli6, Rhoda Au2,4,5,7,8, Michael L Alosco4,5, John Gunstad1. 1. Department of Psychological Sciences, Kent State University, Kent, OH, USA. 2. Framingham Heart Study, Boston University School of Medicine, Boston, MA, USA. 3. Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA. 4. Department of Neurology, Boston University School of Medicine, Boston, MA, USA. 5. Boston University Alzheimer's Disease Center and Boston University CTE Center, Boston University School of Medicine, Boston, MA, USA. 6. Department of Neurology, University of California at Davis Health System, Sacramento, CA, USA. 7. Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA. 8. Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, MA, USA.
Abstract
BACKGROUND: There is growing interest in the pathophysiological processes of preclinical Alzheimer's disease (AD), including the potential role of leptin. Human studies have shown that both low and high levels of leptin can be associated with worse neurocognitive outcomes, suggesting this relationship may be moderated by another risk factor. OBJECTIVE: We examined the association between plasma leptin levels and both neuropsychological test performance and structural neuroimaging and assessed whether body mass index (BMI) is an effect modifier of these associations. METHODS: Our study sample consisted of 2,223 adults from the Framingham Heart Study Third Generation Cohort (average age = 40 years, 53% women). RESULTS: Among the entire sample, there was no association between leptin and any of the neuropsychological domain measures or any of the MRI brain volume measures, after adjustment for BMI, APOE4, and other clinical factors. However, we did observe that BMI category was an effect modifier for the association between leptin and verbal memory (p for interaction = 0.03), where higher levels of leptin were associated with better performance among normal weight participants (BMI 18.5-24.9) kg/m2 (beta = 0.12, p = 0.02). No association was observed between leptin level and verbal memory test performance among participants who were overweight or obese. CONCLUSION: These findings suggest that the association between leptin and cognitive function is moderated by BMI category. Prospective examination of individuals transitioning from middle age to older adulthood will help to clarify the contribution of leptin to AD and other neurodegenerative conditions.
BACKGROUND: There is growing interest in the pathophysiological processes of preclinical Alzheimer's disease (AD), including the potential role of leptin. Human studies have shown that both low and high levels of leptin can be associated with worse neurocognitive outcomes, suggesting this relationship may be moderated by another risk factor. OBJECTIVE: We examined the association between plasma leptin levels and both neuropsychological test performance and structural neuroimaging and assessed whether body mass index (BMI) is an effect modifier of these associations. METHODS: Our study sample consisted of 2,223 adults from the Framingham Heart Study Third Generation Cohort (average age = 40 years, 53% women). RESULTS: Among the entire sample, there was no association between leptin and any of the neuropsychological domain measures or any of the MRI brain volume measures, after adjustment for BMI, APOE4, and other clinical factors. However, we did observe that BMI category was an effect modifier for the association between leptin and verbal memory (p for interaction = 0.03), where higher levels of leptin were associated with better performance among normal weight participants (BMI 18.5-24.9) kg/m2 (beta = 0.12, p = 0.02). No association was observed between leptin level and verbal memory test performance among participants who were overweight or obese. CONCLUSION: These findings suggest that the association between leptin and cognitive function is moderated by BMI category. Prospective examination of individuals transitioning from middle age to older adulthood will help to clarify the contribution of leptin to AD and other neurodegenerative conditions.
Authors: J C Rajapakse; J N Giedd; C DeCarli; J W Snell; A McLaughlin; Y C Vauss; A L Krain; S Hamburger; J L Rapoport Journal: Magn Reson Imaging Date: 1996 Impact factor: 2.546
Authors: Stéphanie Debette; Alexa Beiser; Udo Hoffmann; Charles Decarli; Christopher J O'Donnell; Joseph M Massaro; Rhoda Au; Jayandra J Himali; Philip A Wolf; Caroline S Fox; Sudha Seshadri Journal: Ann Neurol Date: 2010-08 Impact factor: 10.422
Authors: Wolfgang Lieb; Alexa S Beiser; Ramachandran S Vasan; Zaldy S Tan; Rhoda Au; Tamara B Harris; Ronenn Roubenoff; Sanford Auerbach; Charles DeCarli; Philip A Wolf; Sudha Seshadri Journal: JAMA Date: 2009-12-16 Impact factor: 56.272
Authors: William A Banks; Alan B Coon; Sandra M Robinson; Asif Moinuddin; Jessica M Shultz; Ryota Nakaoke; John E Morley Journal: Diabetes Date: 2004-05 Impact factor: 9.461
Authors: Hongzhi Wang; Jung W Suh; Sandhitsu R Das; John B Pluta; Caryne Craige; Paul A Yushkevich Journal: IEEE Trans Pattern Anal Mach Intell Date: 2012-06-26 Impact factor: 6.226
Authors: Michael L Alosco; Mary Beth Spitznagel; Gladys Strain; Michael Devlin; Ronald Cohen; Ross D Crosby; James E Mitchell; John Gunstad Journal: J Clin Neurol Date: 2015-01-02 Impact factor: 3.077
Authors: Francesca Macaluso; Kathleen M Weber; Leah H Rubin; Elaine Dellinger; Susan Holman; Howard Minkoff; Sheila Keating; Lisa R Merlin; Deborah R Gustafson Journal: J Clin Endocrinol Metab Date: 2022-02-17 Impact factor: 5.958
Authors: Azizi A Seixas; Farid Rajabli; Margaret A Pericak-Vance; Girardin Jean-Louis; Robbert L Harms; Ioannis Tarnanas Journal: Front Psychiatry Date: 2022-08-09 Impact factor: 5.435