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June 7, 2026Diabetes

Higher HbA1c shows no independent link to mild cognitive impairment after full covariate adjustment.

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Why the study?

T2D is a risk factor for cognitive impairment, but the role of glycemia changes over time in cognitive impairment risk remains unclear.

Does HbA1c trajectory over 20 years increase the risk of cognitive impairment in adults with prediabetes or T2D?

Population

1,682 middle-aged adults with pre-diabetes at enrollment

Comparison

Longitudinal HbA1c trajectory (intercept and slope)

Design

Cohort study

Follow-up

20 years of follow-up

Key result

Higher mean HbA1c was associated with a higher risk for amnestic mild cognitive impairment independent of demographics (OR 1.77; 95% CI 1.06-2.97; p=0.03), but not after full covariate adjustment.

Authors

ASAllison ShapiroRSRICHARD SHUMTMarinella Temprosa

Discussion

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Overview

Mean HbA1c does not independently predict aMCI after full adjustment; leaves open glycemic effects on cognition in prediabetes.

Key Points

  • This research aims to explore how changes in glycemia over time relate to the risk of cognitive impairment in adults with pre-diabetes or type 2 diabetes.
  • Analyzed 1,682 middle-aged adults with pre-diabetes over 20 years of follow-up.
  • Used random effects model to assess HbA1c trajectories and cognitive impairment classification.
  • Applied multinomial logistic models controlling for demographics and cardiovascular risk factors.
  • Higher mean HbA1c associated with increased risk of amnestic mild cognitive impairment (OR=1.77, 95% CI: 1.06, 2.97, p=0.03).
  • After adjustment, HbA1c was not independently linked to cognitive impairment risk.
  • Older age, male sex, Black race, Hispanic ethnicity, higher SBP, and APOE copy number were related to higher cognitive impairment risk (p<0.05 for all).

Study Design

Type

Cohort (n=1,682)

Structured PICO

Does HbA1c trajectory over 20 years increase the risk of cognitive impairment in adults with prediabetes or T2D?

P
Population
1,682 middle-aged adults with pre-diabetes at enrollment, followed for 20 years to assess the association of longitudinal HbA1c trajectories with cognitive impairment.
E
Exposure
HbA1c trajectory over 20 years of follow-up (intercept and slope)
O
Outcome
Prevalent cognitive impairment (CI) assessed via the National Alzheimer’s Coordinating Center Uniform Data Set (v3) 25 years after enrollmenthard clinical

Main Result

Odds Ratio: 1.77 (95% CI 1.06–2.97)

p-value: p=0.03

Long-term glycemia trajectories in prediabetes and T2D do not independently confer risk for cognitive impairment when accounting for established demographic, genetic, and cardiovascular risk factors.

Cite This Study

Shapiro et al. (2026) conducted a cohort in Pre-diabetes or Type 2 Diabetes (n=1,682). Higher mean HbA1c (glycemia trajectory) vs. Lower mean HbA1c was evaluated on Prevalent cognitive impairment (CI) assessed 25 years after enrollment (OR 1.77, 95% CI 1.06-2.97, p=0.03). Higher mean HbA1c was associated with a higher risk for amnestic mild cognitive impairment independent of demographics (OR 1.77; 95% CI 1.06-2.97; p=0.03), but not after full covariate adjustment.

synapsesocial.com/papers/6a250cd27def13d035e1d0e5https://doi.org/10.2337/db26-2173-p
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