Nat Commun. 2026 Mar 26.
Dafna Pachter,
Hadar Klein,
Omer Kamer,
Dana Tamar Goldberg Toren,
Liav Alufer,
Noa Ebstein Karamani,
Tomer Atlas,
Amit Yaary,
Idan Hagbi,
Yoash Chassidim,
Ilan Shelef,
Moti Salti,
Frauke Beyer,
Veronica Witte,
Assaf Rudich,
Uri Yoel,
Gal Ben-Arie,
Anat Yaskolka Meir,
Alon Kaplan,
Gal Tsaban,
Hila Zelicha,
Carmi Bartal,
Lu Qi,
Matthias Blüher,
Michael Stumvoll,
Uta Ceglarek,
Berend Isermann,
Dong D Wang,
Meir J Stampfer,
Frank B Hu,
Galia Avidan,
Iris Shai.
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).