# Type 2 diabetes and age-related cognitive decline over 40 years in Danish men–A cohort study based on the Danish Aging and Cognition (DanACo) cohort

**Authors:** Gunhild Tidemann Okholm, Marie Grønkjær, Jørgen Rungby, Erik Lykke Mortensen, Merete Osler, Aleksandra Klisic, Aleksandra Klisic, Aleksandra Klisic

PMC · DOI: 10.1371/journal.pone.0340622 · PLOS One · 2026-01-13

## TL;DR

This study found that type 2 diabetes is linked to slightly faster cognitive decline in men over 40 years, based on long-term data from a Danish cohort.

## Contribution

The study provides long-term evidence of cognitive decline in men with type 2 diabetes over an average of 44 years.

## Key findings

- Men with type 2 diabetes had a 1.81 IQ point greater decline compared to those without diabetes.
- Type 2 diabetes was associated with 1.42 times higher odds of significant IQ decline.
- Findings were robust after adjusting for selection bias using inverse probability weights.

## Abstract

The extant literature on type 2 diabetes and cognitive decline is based on short cognitive follow-ups and assessments of baseline cognitive ability after diagnosis. The objective was to investigate the influence of type 2 diabetes on cognitive decline over a period of on average 44 years.

This cohort study included 5,147 men from the Danish Aging and Cognition cohort consisting of a late mid-life (mean age 64.2 years) follow-up of men with intelligence test scores (IQ) available from statutory conscription board examinations in young adulthood (mean age 20.4 years). Follow-up included re-administration of the conscription board intelligence test and a comprehensive questionnaire. Exposure was self-reported but register-based type 2 diabetes and duration of disease were also calculated. Cognitive decline was defined as both IQ change (baseline-follow-up) and significant IQ decline based on the reliable change index (cut-off: 13.2 IQ-points). Associations were analyzed in linear and logistic regression models.

Men having type 2 diabetes had a 1.81 IQ points (95%CI:1.14,2.49) larger decline compared to men without diabetes when adjusting for baseline IQ, years of education, follow-up age, retest interval, depression, and smoking status. Moreover, type 2 diabetes was associated with 1.42 times higher odds of a significant IQ decline and longer duration was associated with a larger, though not statistically significant, decline. The participation rate was 13.4%, and the participants were healthier and more well-educated than non-participants. To account for potential selection bias, inverse probability weights (IPW) were calculated based on baseline characteristics. The analyses applying these weights yielded similar estimates.

Type 2 diabetes was associated with modestly greater cognitive decline and higher odds of a statistically significant (>13.2 IQ points) and clinically relevant decline. Finally, the alignment between main and IPW results indicates the findings are robust and likely generalizable.

## Linked entities

- **Diseases:** type 2 diabetes (MONDO:0005148)

## Full-text entities

- **Diseases:** dementia (MESH:D003704), T2D (MESH:D003924), psychiatric (MESH:D001523), underweight (MESH:D013851), IQ decline (MESH:D060825), inflammation (MESH:D007249), dysfunction of the HPA-axis (MESH:C566610), Cognitive decline (MESH:D003072), prediabetes (MESH:D011236), Depression (MESH:D003866), Diabetes (MESH:D003920), T1D (MESH:D003922)
- **Chemicals:** PONE-D-25-26526 (-), insulin (MESH:D007328)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** DiaKO-19 — Homo sapiens (Human), Prostate carcinoma, Cancer cell line (CVCL_5989), -15 — Cricetulus griseus (Chinese hamster), Spontaneously immortalized cell line (CVCL_UU65)

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12798970/full.md

## References

39 references — full list in the complete paper: https://tomesphere.com/paper/PMC12798970/full.md

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Source: https://tomesphere.com/paper/PMC12798970