Diagnostic, Prognostic, and Mechanistic Biomarkers of Diabetes Mellitus-Associated Cognitive Decline

Abstract

Cognitive dysfunctions such as mild cognitive impairment (MCI), Alzheimer’s disease (AD), and other forms of dementia are recognized as common comorbidities of type 2 diabetes mellitus (T2DM). Currently, there are no disease-modifying therapies or definitive clinical diagnostic and prognostic tools for dementia, and the mechanisms underpinning the link between T2DM and cognitive dysfunction remain equivocal. Some of the suggested pathophysiological mechanisms underlying cognitive decline in diabetes patients include hyperglycemia, insulin resistance and altered insulin signaling, neuroinflammation, cerebral microvascular injury, and buildup of cerebral amyloid and tau proteins. Given the skyrocketing global rates of diabetes and neurodegenerative disorders, there is an urgent need to discover novel biomarkers relevant to the co-morbidity of both conditions to guide future diagnostic approaches. This review aims to provide a comprehensive background of the potential risk factors, the identified biomarkers of diabetes-related cognitive decrements, and the underlying processes of diabetes-associated cognitive dysfunction. Aging, poor glycemic control, hypoglycemia and hyperglycemic episodes, depression, and vascular complications are associated with increased risk of dementia. Conclusive research studies that have attempted to find specific biomarkers are limited. However, the most frequent considerations in such investigations are related to C reactive protein, tau protein, brain-derived neurotrophic factor, advanced glycation end products, glycosylated hemoglobin, and adipokines.

Changes of brain function in patients with type 2 diabetes mellitus measured by different analysis methods: A new coordinate-based meta-analysis of neuroimaging

“…The results showed that the difference between ReHo and ICA/DC was not the primary source of heterogeneity. Previous studies have demonstrated that comprehensive background such as the age, course of disease, education level, emotional disorder, and biomarkers like HbA1c were related to cognitive impairment ( 142 , 143 ). In addition, the brain regions of cortical atrophy in patients with T2DM were also found in early Alzheimer's disease ( 144 ).…”

Sleeve gastrectomy attenuated diabetes-related cognitive decline in diabetic rats

“…Slowly progressive DCD occurs in all age groups, not limited to the aged population ( 30 ). The main pathological features of DCD include hyperphosphorylation of tau and apoptosis of hippocampal neurons, leading to progressive impairment of hippocampal function ( 31 – 33 ). A large number of DCD patients are more likely to present mild cognitive impairment (MCI) or dementia, showing a poor prognosis even after treatment ( 33 , 34 ).…”

“…The main pathological features of DCD include hyperphosphorylation of tau and apoptosis of hippocampal neurons, leading to progressive impairment of hippocampal function ( 31 – 33 ). A large number of DCD patients are more likely to present mild cognitive impairment (MCI) or dementia, showing a poor prognosis even after treatment ( 33 , 34 ). Conventional treatment options for DCD include measurements for lowering blood glucose, lifestyle interventions, and cognitive rehabilitation training.…”

Development of Dementia in Type 2 Diabetes Patients: Mechanisms of Insulin Resistance and Antidiabetic Drug Development

“…AD is more common in diabetic patients than in nondiabetic patients and it is associated with a higher incidence or mortality rate [ 12 ]. The development of dementia and other neurological disorders is common in T2DM, although a sporadic form of dementia is more common ( Table 1 ) [ 13 ]. The pancreatic islets contain alpha and beta cells, which regulate glucagon and insulin, respectively.…”