Cognitive impairment and dementia: a new emerging complication of type 2 diabetes—The diabetologist’s perspective

Abstract

Type 2 diabetes mellitus (T2D) and Alzheimer's disease (AD) are two of the most common diseases of aging around the world. Given the frequency with which T2D and AD occur, the notion that people with T2D may be at increased risk for AD has large societal consequences, and understanding the mechanistic links between these diseases is imperative for the development of effective AD prevention and treatment strategies. Apart from being an accelerator of AD, T2D is associated with a progressive cognitive decline. Impaired insulin signaling, inflammation, the accumulation of advanced glycation end-products and oxidative stress all play an essential role in the pathogenesis of both AD and diabetic complications. Therefore, it is reasonable to postulate that these pathways are involved in the increased risk of dementia that occurs in the T2D population. The early diagnosis of cognitive impairment and the identification of the subset of patients at a higher risk of developing AD is a challenge for healthcare providers, and meeting it will permit us to implement a personalized medicine, which is an essential issue in diabetes care with significant therapeutic implications. The main gaps that should be filled to achieve this objective are examined.

Neurodegeneration in diabetic retinopathy: does it really matter?

“…Numerous epidemiological studies have demonstrated that individuals with type 2 diabetes have a significantly higher risk of developing neurodegenerative diseases, in particular, Alzheimer’s disease [81]. The retina is ontogenically brain-derived tissue, so it may provide an easily accessible and non-invasive way of examining CNS pathology.…”

“…Therefore, it could be postulated that, in individuals who develop brain neurodegeneration, a neurodegenerative process co-occurs in the retina (‘the eye as a window of the brain’). In fact, both diabetes-induced retinal neurodegeneration and Alzheimer’s disease share several pathogenic pathways, such as insulin signalling impairment, low-grade inflammation, the accumulation of advanced glycation end-products (AGEs) and an increase in oxidative stress [81]. In addition, several pathogenic pathways triggered in the brain of those with neurodegenerative diseases have also been found to be triggered in the retinas of individuals with type 2 diabetes [82].…”

“…This pilot study suggested that the assessment of retinal sensitivity by microperimetry could be a useful biomarker for identifying individuals with type 2 diabetes who are at risk of developing Alzheimer’s disease. This is an important issue since unrecognised cognitive dysfunction can affect treatment adherence and diabetes self-management, resulting in poor glycaemic control, an increased frequency of severe hypoglycaemic episodes and increased hospital admissions [81]. For these reasons, the early diagnosis of cognitive impairment is not only recommendable in itself, but also permits a more personalised treatment approach for patients with type 2 diabetes.…”

Reduction of Cognitive Decline in Patients with or at High Risk for Diabetes

“…Intensive research efforts in preclinical models have provided numerous hypotheses about the interaction between insulin resistance and neurodegeneration through a plethora of pathways. There is not enough evidence to provide specific recommendations to prevent the cognitive decline in individuals with or at high risk of type 2 diabetes [80]. …”

Searching cerebrovascular risk indicators for hypertensive patients: Is Framingham Stroke Risk Profile “the magic bullet”?

“…Exclusion of patients with diabetes and atrial fibrillation, frequently associated with high blood pressure, reduce the power of detecting small, but clinically relevant, effects. In fact, both diabetes and atrial fibrillation amplify the impact of blood pressure load on cerebrovascular risk and dementia . However, on clinical grounds, our task is to prevent cerebrovascular complications without too much care of which is the most relevant of the many coexisting patient risk factors.…”