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Abstract
Objectives: For this cross-sectional study, we aimed to elucidate whether higher glycosylated hemoglobin (HbA1c) and glucose levels exert a negative impact on memory performance and hippocampal volume and microstructure in a cohort of healthy, older, nondiabetic individuals without dementia.
Methods: In 141 individuals (72 women, mean age 63.1 years ± 6.9 SD), memory was tested using the Rey Auditory Verbal Learning Test. Peripheral levels of fasting HbA1c, glucose, and insulin and 3-tesla MRI scans were acquired to assess hippocampal volume and microstructure, as indicated by gray matter barrier density. Linear regression and simple mediation models were calculated to examine associations among memory, glucose metabolism, and hippocampal parameters.
Results: Lower HbA1c and glucose levels were significantly associated with better scores in delayed recall, learning ability, and memory consolidation. In multiple regression models, HbA1c remained strongly associated with memory performance. Moreover, mediation analyses indicated that beneficial effects of lower HbA1c on memory are in part mediated by hippocampal volume and microstructure.
Conclusions: Our results indicate that even in the absence of manifest type 2 diabetes mellitus or impaired glucose tolerance, chronically higher blood glucose levels exert a negative influence on cognition, possibly mediated by structural changes in learning-relevant brain areas. Therefore, strategies aimed at lowering glucose levels even in the normal range may beneficially influence cognition in the older population, a hypothesis to be examined in future interventional trials.
GLOSSARY
- AD=
- Alzheimer disease;
- BDI=
- Beck Depression Inventory;
- BMI=
- body mass index;
- DTI=
- diffusion tensor imaging;
- FIRST=
- FMRIB's Integrated Registration and Segmentation Tool;
- HbA1c=
- glycosylated hemoglobin;
- ICV=
- intracranial volume;
- IGT=
- impaired glucose tolerance;
- MD=
- mean diffusivity;
- T2DM=
- type 2 diabetes mellitus
Footnotes
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Supplemental data at www.neurology.org
- Received May 7, 2013.
- Accepted in final form August 14, 2013.
- © 2013 American Academy of Neurology
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- Higher glucose levels associated with lower memory and reduced hippocampal microstructure.
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