What is the clinical evidence from this study?

Study design: Cohort. Population: Obesity and genetic susceptibility (n=35092). Intervention: High-stable obesity trajectory vs. Non-obesity. Primary outcome: Accelerated brain aging (OR 1.90, 95% CI 1.64-2.21).

What does this research mean for the field?

A high-stable obesity trajectory significantly increases the odds of accelerated brain aging, with a stronger effect in males than in females, while transitioning from obesity to non-obesity mitigates this risk even in genetically susceptible individuals. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

September 8, 2026Obesity

High-stable obesity is linked to accelerated brain aging, with ~90% higher odds in males.

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Why the study?

The study aimed to examine the associations of longitudinal obesity trajectories and polygenic risk with sex-specific brain aging.

Do longitudinal obesity trajectories and genetic susceptibility increase the risk of accelerated brain aging in males and females?

Population

35,092 UK Biobank participants (16,484 males and 18,608 females)

Comparison

Longitudinal obesity trajectories and polygenic risk scores

Design

Cohort study

Follow-up

16-year

Key result

A high-stable obesity trajectory increased the odds of accelerated brain aging, with a stronger effect in males (OR 1.90; 95% CI 1.64-2.21) than females (OR 1.25; 95% CI 1.12-1.40).

Authors

MZMingxia Zhu FYFan Yang JGJia Guo

Discussion

Member takes

Overview

Sex-specific obesity trajectories may link to brain aging; leaves open causal inference and any role in clinical risk stratification.

Key Points

To evaluate the individual and joint associations of 16-year longitudinal obesity trajectories and polygenic risk scores with sex-specific brain age acceleration.
Analyzed 35,092 UK Biobank participants (16,484 males and 18,608 females) using sex-specific XGBoost algorithms to estimate multimodal brain age.
Derived 16-year longitudinal obesity trajectories from repeated anthropometric measurements and calculated polygenic risk scores across 55 independent genetic loci.
Conducted multivariable logistic regression to measure associations between obesity patterns, genetic susceptibility, and brain age acceleration.
Accelerated brain aging occurred in 8,198 (49.73%) males and 9,089 (48.84%) females, with high genetic risk increasing the odds of acceleration in both males (OR = 1.39) and females (OR = 1.34).
A high-stable obesity trajectory exhibited a stronger association in males (OR = 1.90, 95% CI: 1.64–2.21) than in females (OR = 1.25, 95% CI: 1.12–1.40), escalating to an OR of 2.78 in males and 1.57 in females when combined with high genetic risk.
Transitioning from obesity to non-obesity reduced the risk of accelerated brain aging by 30% in males and 18% in females.

Study Design

Type

Cohort (n=35,092)

Structured PICO

Do longitudinal obesity trajectories and genetic susceptibility increase the risk of accelerated brain aging in males and females?

Population

35,092 UK Biobank participants followed for 16 years to assess the effects of longitudinal obesity trajectories and polygenic risk on sex-specific brain aging.

Exposure

16-year longitudinal obesity trajectories and polygenic risk scores (based on 55 independent genetic loci)

Comparator

Non-obesity trajectories and lower genetic risk

Outcome

Brain age acceleration (estimated via sex-specific XGBoost models)surrogate

Main Result

Odds Ratio: 1.9 (95% CI 1.64–2.21)

Long-term obesity is a critical, sex-dimorphic driver of accelerated brain aging, and midlife weight management offers robust neuroprotection even in genetically susceptible individuals.

Cite This Study

Zhu et al. (2026) conducted a cohort in Obesity and genetic susceptibility (n=35,092). High-stable obesity trajectory vs. Non-obesity was evaluated on Accelerated brain aging (OR 1.90, 95% CI 1.64-2.21). A high-stable obesity trajectory increased the odds of accelerated brain aging, with a stronger effect in males (OR 1.90; 95% CI 1.64-2.21) than females (OR 1.25; 95% CI 1.12-1.40).

synapsesocial.com/papers/6aa0091858e84d0ff5b47b30 https://doi.org/10.1002/oby.70304

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September 8, 2026Obesity

High-stable obesity is linked to accelerated brain aging, with ~90% higher odds in males.

View Full Paper

Ask AI

Bookmark

Why the study?

The study aimed to examine the associations of longitudinal obesity trajectories and polygenic risk with sex-specific brain aging.

Do longitudinal obesity trajectories and genetic susceptibility increase the risk of accelerated brain aging in males and females?

Population

35,092 UK Biobank participants (16,484 males and 18,608 females)

Comparison

Longitudinal obesity trajectories and polygenic risk scores

Design

Cohort study

Follow-up

16-year

Key result

A high-stable obesity trajectory increased the odds of accelerated brain aging, with a stronger effect in males (OR 1.90; 95% CI 1.64-2.21) than females (OR 1.25; 95% CI 1.12-1.40).

Authors

MZMingxia Zhu FYFan Yang JGJia Guo

Discussion

Member takes

Overview

Sex-specific obesity trajectories may link to brain aging; leaves open causal inference and any role in clinical risk stratification.

Key Points

To evaluate the individual and joint associations of 16-year longitudinal obesity trajectories and polygenic risk scores with sex-specific brain age acceleration.
Analyzed 35,092 UK Biobank participants (16,484 males and 18,608 females) using sex-specific XGBoost algorithms to estimate multimodal brain age.
Derived 16-year longitudinal obesity trajectories from repeated anthropometric measurements and calculated polygenic risk scores across 55 independent genetic loci.
Conducted multivariable logistic regression to measure associations between obesity patterns, genetic susceptibility, and brain age acceleration.
Accelerated brain aging occurred in 8,198 (49.73%) males and 9,089 (48.84%) females, with high genetic risk increasing the odds of acceleration in both males (OR = 1.39) and females (OR = 1.34).
A high-stable obesity trajectory exhibited a stronger association in males (OR = 1.90, 95% CI: 1.64–2.21) than in females (OR = 1.25, 95% CI: 1.12–1.40), escalating to an OR of 2.78 in males and 1.57 in females when combined with high genetic risk.
Transitioning from obesity to non-obesity reduced the risk of accelerated brain aging by 30% in males and 18% in females.

Study Design

Type

Cohort (n=35,092)

Structured PICO

Do longitudinal obesity trajectories and genetic susceptibility increase the risk of accelerated brain aging in males and females?

Population

35,092 UK Biobank participants followed for 16 years to assess the effects of longitudinal obesity trajectories and polygenic risk on sex-specific brain aging.

Exposure

16-year longitudinal obesity trajectories and polygenic risk scores (based on 55 independent genetic loci)

Comparator

Non-obesity trajectories and lower genetic risk

Outcome

Brain age acceleration (estimated via sex-specific XGBoost models)surrogate

Main Result

Odds Ratio: 1.9 (95% CI 1.64–2.21)

Long-term obesity is a critical, sex-dimorphic driver of accelerated brain aging, and midlife weight management offers robust neuroprotection even in genetically susceptible individuals.

Cite This Study

synapsesocial.com/papers/6aa0091858e84d0ff5b47b30 https://doi.org/10.1002/oby.70304

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