# Headache associated with adverse cognitive trajectories in Chinese aging cohort: a group-based trajectory modeling study

**Authors:** Hong Wang, Weisheng Deng, Wei Qiu

PMC · DOI: 10.1007/s10072-026-08922-8 · 2026-03-07

## TL;DR

This study finds that headache is linked to worse cognitive decline in older Chinese adults, with alcohol and hypertension increasing the risk.

## Contribution

The novel use of group-based trajectory modeling reveals headache's role in predicting adverse cognitive trajectories.

## Key findings

- Headache increases the likelihood of low and medium cognitive trajectories in aging adults.
- Alcohol, hypertension, and stroke amplify the cognitive risk associated with headache.
- Diabetes unexpectedly reduces the risk of adverse cognitive trajectories linked to headache.

## Abstract

Conflicting evidence exists regarding the associations between headache- and cognition, with conventional methods failing to capture the heterogeneous cognitive trajectories. We investigated dynamic relationships using group-based trajectory modeling (GBTM).

This longitudinal analysis included 2,949 participants aged ≥45 from the China Health and Retirement Longitudinal Study (CHARLS, 2011-2020). Headache was ascertained via a standardized questionnaire. Cognitive trajectories were derived from global cognition Z-scores using GBTM. Multinomial logistic regression evaluated headache-cognition associations, adjusting for demographics, health behaviors, and comorbidities. Stratified analyses tested effect modification by demographics, health behaviors, and comorbidities

GBTM identified three cognitive trajectories: low (17.5%), medium (43.8%), and high (38.7%). Headache significantly increased the probability of belonging to low (OR = 1.29, 95% CI: 1.11–1.50; p < 0.001) and medium trajectories (OR = 1.14, 95% CI: 1.01–1.30; p = 0.033). Alcohol, hypertension, and stroke amplified associations, while diabetes paradoxically attenuated them (p for interaction < 0.05).

Headache independently predicts adverse cognitive trajectories, with alcohol, hypertension, and stroke acting as critical effect modifiers. Paradoxically, diabetes attenuated this risk. Integrating headache screening into cognitive risk stratification and targeting modifiable factors may mitigate cognitive risk.

The online version contains supplementary material available at 10.1007/s10072-026-08922-8.

## Linked entities

- **Diseases:** stroke (MONDO:0005098), diabetes (MONDO:0005015)

## Full-text entities

- **Genes:** PRKAA1 (protein kinase AMP-activated catalytic subunit alpha 1) [NCBI Gene 5562] {aka AMPK, AMPK alpha 1, AMPKa1}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, CALCA (calcitonin related polypeptide alpha) [NCBI Gene 796] {aka CALC1, CGRP, CGRP-I, CGRP-alpha, CGRP1, CT}, MAPT (microtubule associated protein tau) [NCBI Gene 4137] {aka DDPAC, FTD1, FTDP-17, MAPTL, MSTD, MTBT1}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, TLR4 (toll like receptor 4) [NCBI Gene 7099] {aka ARMD10, CD284, TLR-4, TOLL}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}
- **Diseases:** dementia (MESH:D003704), CSD (MESH:D003866), neuronal injury (MESH:D009410), Chronic conditions (MESH:D002908), cognitive decline (MESH:D003072), migraine (MESH:D008881), hypertension (MESH:D006973), CHARLS (OMIM:603663), Stroke (MESH:D020521), white matter damage (MESH:D056784), metabolic (MESH:D008659), pain (MESH:D010146), Headache (MESH:D006261), inflammatory (MESH:D007249), neuroinflammation (MESH:D000090862), Headache disorders (MESH:D020773), diabetes (MESH:D003920)
- **Chemicals:** Alcohol (MESH:D000438), nicotine (MESH:D009538), metformin (MESH:D008687)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12966203/full.md

---
Source: https://tomesphere.com/paper/PMC12966203