Cognitive decline and dementia in diabetes mellitus: mechanisms and clinical implications

Abstract

<p class="first" id="P1">Cognitive dysfunction is increasingly recognized as an important comorbidity of diabetes mellitus. Different stages of diabetes-associated cognitive dysfunction can be discerned, with different cognitive features, affected age groups, prognosis, and likely also different underlying mechanisms. Relatively subtle, slowly progressive cognitive decrements occur in all age groups. More severe stages, particularly mild cognitive impairment and dementia, with progressive deficits, occur primarily in older individuals. The latter are clearly most relevant for patient management and are the focus of this review. </p><p id="P2">Evolving insights from studies on risk factors, brain imaging, and neuropathology provide important clues on mechanisms. In the majority of patients multiple etiologies likely determine the cognitive phenotype. Although both the risk of -clinically diagnosed- Alzheimer’s disease and that of vascular dementia is increased in association with diabetes, the cerebral burden of the prototypical Alzheimer’s pathologies is not. A major challenge is therefore to pinpoint from the spectrum of diabetes-related disease processes those that affect the brain and contribute to development of dementia beyond Alzheimer’s pathologies. Observations from experimental models can help to meet that challenge, but this requires further improving the synergy between experimental and clinical scientists. Development of targeted treatment and preventive strategies depends on these translational efforts. </p>