Cognitive decline and dementia in diabetes mellitus: mechanisms and clinical implications
By Geert Jan Biessels, F. Despa. Nature Reviews Endocrinology, 2018
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Cognitive dysfunction is increasingly recognized as an important comorbidity of diabetes mellitus. Different stages of diabetes-associated cognitive dysfunction exist, each with different cognitive features, affected age groups and prognoses and probably with 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 (>65 years of age). Patients in the latter group are the most relevant for patient management and are the focus of this Review. Here, we review the evolving insights from studies on risk factors, brain imaging and neuropathology, which provide important clues on mechanisms of both the subtle cognitive decrements and the more severe stages of cognitive dysfunction. In the majority of patients, the cognitive phenotype is probably defined by multiple aetiologies. Although both the risk of clinically diagnosed Alzheimer disease and that of vascular dementia is increased in association with diabetes, the cerebral burden of the prototypical pathologies of Alzheimer disease (such as neurofibrillary tangles and neuritic plaques) is not. A major challenge for researchers is to pinpoint from the spectrum of diabetes-related disease processes those that affect the brain and contribute to development of dementia beyond the pathologies of Alzheimer disease. Observations from experimental models can help to meet that challenge, but this requires further improving the synergy between experimental and clinical scientists. The development of targeted treatment and preventive strategies will therefore depend on these translational efforts.Cognitive dysfunction is an important comorbidity of diabetes mellitus. In this Review, Geert Jan Biessels and Florin Despa discuss the different manifestations of diabetes-mellitus-associated cognitive dysfunction. They also review the role of experimental models in improving our understanding of the pathophysiological mechanisms.Key pointsCognitive dysfunction in diabetes mellitus can manifest itself as diabetes-associated cognitive decrements, mild cognitive impairment (MCI) and dementia.Owing to the marked differences in affected age groups and trajectories of cognitive decline, diabetes-mellitus-associated cognitive decrements and dementia should be regarded as different entities that probably have different underlying mechanisms.Mechanisms of MCI and dementia in diabetes have mainly been studied in patients with type 2 diabetes mellitus (T2DM) and involve mixed vascular and neurodegenerative pathologies, often on a background of Alzheimer disease pathology; however, T2DM does not increase the burden of the latter.Key causative pathways in diabetes-associated cognitive dysfunction need to be identified in order to develop course-modifying therapies.Experimental models can single out individual causative pathways in ways and at a level of detail that are impossible in humans.Any potential mechanisms of brain dysfunction that are identified in experimental models of diabetes mellitus must also be evaluated in the complex setting of other morbidities with which they may co-occur in patients.
Subfields: Neurology, Physiology, Psychiatry and Mental health
View Paper: https://www.semanticscholar.org/paper/13a78a2961e8f77a3fbd05610daa6705be163610
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Citations in the corpus
- Vascular Cognitive Impairment and Dementia (2019, background): “Indeed, diabetes seems to primarily increases the burden of cerebrovascular pathology, but not the frequency of Alzheimer’s pathology (42).”