Vol 55, No 5 (2021)
Review Article
Published online: 2021-08-06

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Alzheimer’s disease and type 2 diabetes mellitus: similarities in pathomechanisms lead to therapeutic opportunities

Krzysztof Bednarz1, Joanna Siuda1
Pubmed: 34355790
Neurol Neurochir Pol 2021;55(5):418-428.

Abstract

Introduction. Type 2 diabetes mellitus is a metabolic disease the development of which depends on both environmental and genetic factors. The rapid increase in the number of cases observed in recent decades has been associated with the lifestyle predominant in the West, characterised by a high-calorie diet rich in carbohydrates and saturated fatty acids as well as little physical activity and chronic stress. Another disease with growing morbidity is Alzheimer’s disease, a neurodegenerative disorder characterised by progressive dementia.

State of the art. The results of numerous studies indicate many similarities between these two diseases in terms of their pathomechanisms, especially changes in the activity of enzymatic pathways, accumulation of peptides with altered structure, and chronic inflammation. Amyloid β, hyperphosphorylated tau protein, amylin, and apolipoprotein J are involved in both pathologies. The reasons for their excessive accumulation are not fully understood, but cellular metabolism disorders associated with insulin resistance and diabetes mellitus may play a key role in this process.
It is highly probable that the changes observed at cellular level, which translate into the clinical state of patients, are caused by many abnormalities common to both diseases.

Clinical implications. The discovery of pathophysiological similarities has resulted in attempts to use antidiabetic drugs in Alzheimer’s disease therapy. While animal studies have revealed the potential benefits of oral antidiabetic drugs, studies on humans have not provided clear data regarding their effectiveness. Most clinical trial results are promising, but there have also been studies that have shown no significant, or even adverse, effects of these drugs on Alzheimer’s disease course.

Future directions. Undoubtedly, further research is needed to better understand the mechanisms by which the medications used in diabetes treatment affect the nervous system, and further clinical trials to compare the effectiveness of this therapy in patients presenting different clinical conditions at different stages of Alzheimer’s disease.

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