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Review
. 2014 Jul;35(7):995-1001.
doi: 10.1007/s10072-014-1797-2. Epub 2014 Apr 29.

Diabetes and the brain: issues and unmet needs

Natan M Bornstein  1 , Michael Brainin, Alla Guekht, Ingmar Skoog, Amos D Korczyn
Affiliations
Review

Diabetes and the brain: issues and unmet needs

Natan M Bornstein et al. Neurol Sci. 2014 Jul.

Abstract

Diabetes mellitus (DM) is associated with an increased risk of mild cognitive impairment, dementia and stroke. The association between DM and dementia appears to be stronger for vascular cognitive impairment than for Alzheimer's disease, suggesting cerebrovascular disease may be an important factor in cognitive impairment in DM. Although the exact mechanisms by which DM affects the brain remain unclear, changes to brain vasculature, disturbances of cerebral insulin signaling, insulin resistance, glucose toxicity, oxidative stress, accumulation of advanced glycation end products, hypoglycemic episodes, and alterations in amyloid metabolism may all be involved. Cognitive impairment and dementia associated with DM may also be mediated via vascular risk factors, in particular brain ischemia, the occurrence of which can have an additive or synergistic effect with concomitant neurodegenerative processes. To date, no drug has been approved for the treatment of vascular dementia and there are no specific pharmacological treatments for preventing or reducing cognitive decline in patients with DM. Most focus has been on tighter management of vascular risk factors, although evidence of reduced cognitive decline through reducing blood pressure, lipid-lowering or tighter glycemic control is inconclusive. Tailored, multimodal therapies may be required to reduce the risk of cognitive dysfunction and decline in patients with DM. The use of pleiotropic drugs with multimodal mechanisms of action (e.g., cerebrolysin, Actovegin) may have a role in the treatment of cognitive dysfunction and their use may warrant further investigation in diabetic populations.

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Figures

Fig. 1
Fig. 1
Potential causes of cognitive impairment in type 2 diabetes. Adapted from [17]
Fig. 2
Fig. 2
Potential effects of hyperglycaemia over time on pathological development of cerebral infarction (reproduced with permission from [27])
Fig. 3
Fig. 3
Outcomes in the ACCORD-MIND study [46]. a Digit symbol substitution test (DSST). b Total brain volume
See this image and copyright information in PMC

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