A Longitudinal Investigation of Prediabetes, Diabetes, HbA1c and Cognitive Trajectories Among Cognitively Unimpaired Individuals

Background
Previous studies on the relationship between prediabetes, HbA1c and cognitive trajectories show mixed results. Therefore, we investigated the association of prediabetes, diabetes and HbA1c with change in global and domain-specific cognitive scores in cognitively unimpaired (CU) adults, as well as the potential effect modification by sex or age.

Methods
This longitudinal study included 4236 CU persons aged ≥ 50 years from the population-based Mayo Clinic Study of Aging. We ran linear mixed-effect models with baseline prediabetes, diabetes and HbA1c predicting longitudinal global and domain-specific (i.e., memory, language, attention/executive function, and visuospatial skills) cognitive z-scores and raw scores. Models were adjusted for age, sex, education, medical comorbidity, repeated cognitive testing, and ApoEɛ4. We additionally ran models with sex and age interactions.

Results
Compared to normoglycemic individuals, individuals with prediabetes and diabetes showed poorer performance on cognitive tests, i.e., TMT-B, category fluency, and block design subtest over time. Additionally, the presence of prediabetes, diabetes, longer diabetes duration and higher HbA1c were associated with faster global and domain-specific cognitive decline over a median follow-up of 6.4 years (range 1–19). ... mehrThree-way interactions showed that the effect of diabetes on decline in global cognition, attention and visuospatial domains was more pronounced in women than in men. Age did not modify the effect of diabetes or higher HbA1c on cognition.

Conclusions
The results suggest that prediabetes and diabetes significantly shorten the timeframe before a potentially clinically noticeable change in global and domain-specific cognition is reached. Thus, lifestyle modification to reverse prediabetes and prevent diabetes could potentially reduce the rate of cognitive decline in aging populations. The findings differed by sex (i.e., the effect of diabetes on decline in global cognition, attention and visuospatial domains was more pronounced in women than men).