Journal Article

Leptin bioavailability and markers of brain atrophy and vascular injury in the middle age

Himali, Jayandra J., Kautz, Tiffany F., Mathews, Julia, Aslam, Asra, DeCarli, Charles, Maillard, Pauline, Ramachandran, Vasan S., Seshadri, Sudha, Beiser, Alexa S., Satizabal, Claudia L., Luckey, Alison M., Shipp, Eric L., Dediós, Angel Gabriel Velarde, Short, Meghan I., Habes, Mohamad, Bernal, Rebecca, Scarmeas, Nikolaos, Treviño, Hector A., Charisis, Sokratis, Muhammad, Jazmyn A. S.

2024

Overview

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.

• Publisher: John Wiley and Sons Inc
• Subject: Atrophy - pathology / Biomarkers / Brain - diagnostic imaging / Brain - pathology / cognition / DTI / Female / fractional anisotropy / free leptin index / free water / Humans / leptin / Leptin - blood / leptin bioavailability / leptin perturbations / leptin receptor / Magnetic Resonance Imaging / Male / MarkVCID / mean diffusivity / Middle Aged / MRI / neuropsychological evaluation / Neuropsychological Tests / peak width of skeletonized mean diffusivity / Receptors, Leptin / the Framingham Heart Study / white matter microstructural integrity