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Higher glucose levels associated with lower memory and reduced hippocampal microstructure

  1. Agnes Flöel, MD
  1. From the Departments of Neurology (L.K., A.V.W., A.W., A.F.) and Biostatistics and Clinical Epidemiology (U.G.), NeuroCure Cluster of Excellence (A.V.W., A.F.), and Center for Stroke Research Berlin (U.G., A.F.), Charité–University Medicine, Berlin; and Department of Psychiatry (D.R.), University of Halle, Germany.
  1. Correspondence to Dr. Flöel: agnes.floeel{at}charite.de or Ms. Kerti: lucia.kerti{at}charite.de
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  1. (1) German society for neurology, compensation for travel related expenses (conference talks 2010 and 2011)

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Funding for Travel or Speaker Honoraria:

  1. (1) German Society for Neurology, travel compensations for conference talks, 2010-12, (2) Alzheimer's Association, travel grant for conference talk, 2012, (3) German National Academic Foundation, compensation for educational course, 2012, (4) Sport-Gesundheitspark Berlin e.V., honoraria for a symposium's talk, 2012

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  1. (1) Federal Ministry of Education and Research, FKZ 0315673, Co-PI, 2010-13

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  1. NONE

Research Support, Foundations and Societies:

  1. German Research Foundation, FL 379/8-1, Co-PI, 2009-present

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  1. NONE

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Funding for Travel or Speaker Honoraria:

  1. (1) German society for neurology, compensation for travel related expenses (conference talk 2012)

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  1. I received funding from the Center for Rusmiddelforskning Aarhus University, Denmark, from the Albrecht-Kossel-Institute for Neuroregeneration Rostock University, Germany and from the Federal Ministry of Education and Research via the Grant Center for Stroke Research Berlin (01 EO 0801).

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  1. F.Hoffmann-La Roche Advisory Board

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  1. F.Hoffmann-La Roche Advisory Board

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  1. International Journal of Neuropsychopharmacology (CINP) Field Editor for Molecular Psychiatry of the World Journal of Biological Psychiatry BMC Medical Genetics European Neuropsychopharmacology (ECNP) Suizidprophylaxe European Archives of Psychiatry and Clinical Neuroscience

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  1. Received one-time speaker honoraria (between 500 and 1000 Euro) for oral presentations from Novartis, B?hringer-Ingelheim and Souvenaid (commercial entities). not related to present study

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  1. Royalties from the book ?Alzheimer- Unabwendbares Schicksal?? from 2012 onwards (less than 3000 Euro total) not related to present study

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  1. Received one-time consulting fees from Schwabe (1500 Euro, commercial entity). not related to present study

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  1. This work was supported by grants from the Deutsche Forschungsgemeinschaft (Fl 379-8/1, Fl 379-10/1, Fl 279-11/1; and DFG-Exc 257), the Else-Kr?ner Fresenius Stiftung (2009-141 ; 2011-119), and the Bundesministerium f?r Bildung und Forschung (FKZ 0315673A, 01EO0801 and 01GY1144).

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  1. ↵* These authors contributed equally to this work.

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.

  • Received May 7, 2013.
  • Accepted in final form August 14, 2013.
  1. Published online before print October 23, 2013, doi: 10.1212/01.wnl.0000435561.00234.ee Neurology 10.1212/01.wnl.0000435561.00234.ee
  1. » Abstract
  2. Full Text (PDF)
  3. Data Supplement
  4. Abstract in Arabic

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