Links to Cognitive Deficits in Type 2 Diabetes

The glymphatic system has recently been shown to clear brain extracellular solutes and abnormalities in glymphatic clearance system may contribute to both initiation and progression of neurological diseases. Despite that diabetes is known as a risk factor for vascular diseases, little is known how diabetes affects the glymphatic system. The current study is the first investigation of the effect of diabetes on the glymphatic system and the link between alteration of glymphatic clearance and cognitive impairment in Type-2 diabetes mellitus rats. MRI analysis revealed that clearance of cerebrospinal fluid contrast agent Gd-DTPA from the interstitial space was slowed by a factor of three in the hippocampus of Type-2 diabetes mellitus rats compared to the non-DM rats and confirmed by florescence imaging analysis. Cognitive deficits detected by behavioral tests were highly and inversely correlated to the retention of Gd-DTPA contrast and fluorescent tracer in the hippocampus of Type-2 diabetes mellitus rats. Type-2 diabetes mellitus suppresses clearance of interstitial fluid in the hippocampus and hypothalamus, suggesting that an impairment of the glymphatic system contributes to Type-2 diabetes mellitus-induced cognitive deficits. Whole brain MRI provides a sensitive, non-invasive tool to quantitatively evaluate cerebrospinal fluid and interstitial fluid exchange in Type-2 diabetes mellitus and possibly in other neurological disorders, with potential clinical application.

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In Addition to Poor Glycemic Control, a High Level of Irisin in the Plasma Portends Early Cognitive Deficits Clinically in Chinese Patients With Type 2 Diabetes Mellitus

Frontiers in Endocrinology ◽

10.3389/fendo.2019.00634 ◽

2019 ◽

Vol 10 ◽

Author(s):

Hongyan Lin ◽

Yang Yuan ◽

Sai Tian ◽

Jing Han ◽

Rong Huang ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Glycemic Control ◽

Cognitive Deficits ◽

Poor Glycemic Control ◽

Chinese Patients ◽

High Level

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Decreased plasma level of lipoprotein lipase predicted verbal disfluency in Chinese type 2 diabetes mellitus patients with early cognitive deficits

Current Alzheimer Research ◽

10.2174/1567205018666210922105850 ◽

2021 ◽

Vol 18 ◽

Author(s):

Ke An ◽

Peng Guo ◽

Haoqiang Zhang ◽

Wenwen Zhu ◽

Wuyou Cao ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Plasma Level ◽

Lipoprotein Lipase ◽

Cognitive Deficits ◽

Amyloid Β ◽

Chinese Patients ◽

Control Group

Background : Lipoprotein lipase (LPL) is the rate-limiting enzyme of catalyzing the hydrolysis of triglycerides and contributes to amyloid-β formation which shows promise as a pathological factor of cognitive decline in type 2 diabetes mellitus (T2DM). This study aimed to investigate the pathogenetic roles of LPL and rs328 polymorphism in mild cognitive impairment (MCI) in patients with T2DM. Methods: Chinese patients with T2DM were recruited and divided into two groups based on Montreal Cognitive Assessment score. Demographic data were collected, LPL was measured and neuropsychological test results were examined. Results: Seventy-nine patients with diabetes and MCI had signiﬁcantly decreased plasma LPL levels (p = 0.007) when compared with health-cognition controls (n = 91). Correlation analysis revealed that LPL was positively correlated with clock drawing test (r = 0.158, p = 0.043) and logical memory test (r = 0.162, p = 0.037), while lipoprotein a (r = -0.214, p = 0.006) was inversely associated with LPL. Logistic regression analysis further demonstrated that LPL concentration was an independent factor for diabetic MCI (p = 0.036). No significant differences were observed in the distributions of rs328 variants between patients with MCI and the controls. Moreover, no remarkable association was found among plasma LPL levels, cognitive performances, and lipid levels between the genotypic subgroups. The trail making tests A was increased in the GC group when compared with the CC genotype in the control group. Conclusion: Decreased plasma level of LPL could probably predict early cognitive deficits, especially verbal disfluency.

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DIABETIC ENCEPHALOPATHY IN TYPE 2 DIABETES

Journal of Medicine and Pharmacy ◽

10.34071/jmp.2016.6.8 ◽

2017 ◽

pp. 52-58

Author(s):

Van Vy Hau Nguyen ◽

Hai Thuy Nguyen ◽

Dinh Toan Nguyen

Keyword(s):

Type 2 Diabetes ◽

Cognitive Deficits ◽

Organ Damage ◽

Diabetic Encephalopathy ◽

Downstream Effects ◽

Increased Risk ◽

Underlying Mechanisms ◽

The Brain

Type 2 diabetes is a common metabolic disease with a rising global prevalence. It is associated with slowly progressive end-organ damage in the eyes and kidneys, but also in the brain. The latter complication is often referred to as "diabetic encephalopathy" and is characterized by mild to moderate impairments in cognitive functioning. It is also associated with an increased risk of dementia. Diabetic encephalopathies are now accepted complications of diabetes. To date, its pathogenetic mechanisms are largely unclear. They appear to differ in type 1 and type 2 diabetes as to underlying mechanisms and the nature of resulting cognitive deﬁcits. The increased incidence of Alzheimer’s disease in type 2 diabetes is associated with insulin resistance, hyperinsulinemia and hyperglycemia, and commonly accompanying attributes such as hypercholesterolemia, hypertension and obesity. However, cognitive impairement in type 1 diabetes have other differences with type 2 diabetes. The major underlying component here appears to be insulin deﬁciency with downstream effects on the expression of neurotrophic factors, neurotransmitters, oxidative and apoptotic stressors resulting in defects in neuronal integrity, connectivity and loss commonly occurring in the still developing brain.

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Type 2 diabetes mellitus accelerates brain aging and cognitive decline: complementary findings from UK Biobank and meta-analyses.

10.1101/2021.05.23.21257682 ◽

2021 ◽

Author(s):

Liam P McMahon ◽

Botond Antal ◽

Syed Fahad Sultan ◽

Andrew Lithen ◽

Deborah J Wexler ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Cognitive Deficits ◽

Brain Aging ◽

Premotor Cortex ◽

Normal Brain ◽

Aging Effects ◽

Functional Changes

Type 2 diabetes mellitus is known to be associated with cognitive deficits; however, their extent, overlap with aging effects, and neurobiological correlates are currently unknown. We characterized neurocognitive effects in T2DM in a large cohort complemented by meta-analysis of the published literature. As compared to age, sex, and education-matched HC, T2DM was associated with marked cognitive deficits, particularly in executive functioning and processing speed. Likewise, we found that the diagnosis of T2DM was significantly associated with gray matter atrophy, primarily within the ventral striatum, cerebellum, and putamen, with reorganization of brain activity (decreased in the caudate, frontal eye fields, and premotor cortex and increased in the subgenual area, thalamus, brainstem and posterior cingulate cortex). The structural and functional changes associated with T2DM show marked overlap with the effects of aging but appear earlier, with disease duration linked to more severe neurodegeneration. The neurocognitive impact of T2DM suggests marked acceleration of normal brain aging, by approximately 24%, made worse with chronicity. As such, neuroimaging-based biomarkers may provide a valuable adjunctive measure of T2DM progression and treatment efficacy based on neurological outcomes.

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