Sokratis Charisis, Meghan I. Short, Rebecca Bernal, Tiffany F. Kautz, Hector A. Treviño, Julia Mathews, Angel Gabriel Velarde Dediós, Jazmyn A. S. Muhammad, Alison M. Luckey, Asra Aslam, Jayandra J. Himali, Eric L. Shipp, Mohamad Habes, Alexa S. Beiser, Charles DeCarli, Nikolaos Scarmeas, Vasan S. Ramachandran, Sudha Seshadri, Pauline Maillard, Claudia L. Satizabal
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Abstract
INTRODUCTION
We investigated the associations of leptin markers with cognitive function and magnetic resonance imaging (MRI) measures of brain atrophy and vascular injury in healthy middle-aged adults.
METHODS
We included 2262 cognitively healthy participants from the Framingham Heart Study with neuropsychological evaluation; of these, 2028 also had available brain MRI. Concentrations of leptin, soluble leptin receptor (sOB-R), and their ratio (free leptin index [FLI]), indicating leptin bioavailability, were measured using enzyme-linked immunosorbent assays. Cognitive and MRI measures were derived using standardized protocols.
RESULTS
Higher sOB-R was associated with lower fractional anisotropy (FA, β = −0.114 ± 0.02, p < 0.001), and higher free water (FW, β = 0.091 ± 0.022, p < 0.001) and peak-width skeletonized mean diffusivity (PSMD, β = 0.078 ± 0.021, p < 0.001). Correspondingly, higher FLI was associated with higher FA (β = 0.115 ± 0.027, p < 0.001) and lower FW (β = -0.096 ± 0.029, p = 0.001) and PSMD (β = -0.085 ± 0.028, p = 0.002).
DISCUSSION
Higher leptin bioavailability was associated with better white matter (WM) integrity in healthy middle-aged adults, supporting the putative neuroprotective role of leptin in late-life dementia risk.
Highlights
Higher leptin bioavailability was related to better preservation of white matter microstructure.
Higher leptin bioavailability during midlife might confer protection against dementia.
Potential benefits might be even stronger for individuals with visceral obesity.
DTI measures might be sensitive surrogate markers of subclinical neuropathology.
期刊介绍：
Alzheimer's & Dementia is a peer-reviewed journal that aims to bridge knowledge gaps in dementia research by covering the entire spectrum, from basic science to clinical trials to social and behavioral investigations. It provides a platform for rapid communication of new findings and ideas, optimal translation of research into practical applications, increasing knowledge across diverse disciplines for early detection, diagnosis, and intervention, and identifying promising new research directions. In July 2008, Alzheimer's & Dementia was accepted for indexing by MEDLINE, recognizing its scientific merit and contribution to Alzheimer's research.
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