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Pachter, D.* ; Klein, H.* ; Kamer, O.* ; Goldberg Toren, D.T.* ; Alufer, L.* ; Ebstein Karamani, N.* ; Atlas, T.* ; Yaary, A.* ; Hagbi, I.* ; Chassidim, Y.* ; Shelef, I.* ; Salti, M.* ; Beyer, F.* ; Witte, V.* ; Rudich, A.* ; Yoel, U.* ; Ben-Arie, G.* ; Yaskolka Meir, A.* ; Kaplan, A.* ; Tsaban, G.* ; Zelicha, H.* ; Bartal, C.* ; Qi, L.* ; Blüher, M. ; Stumvoll, M.* ; Ceglarek, U.* ; Isermann, B.* ; Wang, D.D.* ; Stampfer, M.J.* ; Hu, F.B.* ; Avidan, G.* ; Shai, I.*

Sustained visceral fat loss is associated with attenuated brain atrophy and improved cognitive function in late midlife.

Nat. Commun. 17:4434 (2026)

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We examined whether long-term exposure to visceral-adipose-tissue (VAT) influences brain atrophy and cognitive performance years after lifestyle intervention. In the Follow-Interventions-Trials (FIT) project, 533 adults (age=61.4 y, 86% men) from four prior 18-24-month lifestyle randomized-clinical-trials underwent abdominal/brain magnetic-resonance-imaging (MRI)s and Montreal-Cognitive-Assessment (MoCA) testing 5-16 y after interventions. Lower VAT exposure, calculated by area-under-the-curve, from baseline, post-intervention, and follow-up, independently resulted in higher MoCA scores. VAT loss during intervention predicted higher brain volumes at follow-up, independent of weight loss. Among participants with three brain and VAT MRI scans, lower long-term VAT was associated with a slower rate of brain atrophy. These patterns were not observed for deep/superficial subcutaneous-adipose-tissues. Improved glycemic control parameters, rather than lipid or inflammatory markers, were mostly related to the favorable longitudinal brain outcomes. This long-term, large-scale intervention and follow-up MRI study suggests that sustained visceral fat loss, rather than weight loss, is linked to better cognition and attenuation of brain atrophy years later, mainly via improved glycemic control. Trial registration: DIRECT (Clinical-trials-identifier: NCT00160108); CASCADE (Clinical-trials-identifier: NCT00784433); CENTRAL (Clinical-trials-identifier: NCT01530724); DIRECT-PLUS (Clinical-trials-identifier: NCT03020186).

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Publication type Article: Journal article

Document type Scientific Article

Keywords Adipose-tissue; Adults; Inflammation

ISSN (print) / ISBN 2041-1723

e-ISSN 2041-1723

Journal Nature Communications

Quellenangaben Volume: 17, Issue: 1, Article Number: 4434

Publisher Springer

Publishing Place London

Reviewing status Peer reviewed

Institute(s) Helmholtz Institute for Metabolism, Obesity and Vascular Research (HI-MAG)

Grants B11
project number 209933838 - SFB 1052
This work was supported by grants from the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy - EXC-3105/1 - 533765739 to I. Shai, M. Stumvoll, and M. Blher