scholarly journals Oxidized cholesterol species as signaling molecules in the brain: diabetes and Alzheimer’s disease

2019 ◽  
Vol 3 (4) ◽  
Author(s):  
Thaddeus K. Weigel ◽  
Joshua A. Kulas ◽  
Heather A. Ferris
Keyword(s):  
Alzheimer’S Disease ◽  
Type 2 Diabetes ◽  
Alzheimer's Disease ◽  
Cholesterol Oxidation ◽  
Oxidized Cholesterol ◽  
Increased Risk ◽  
Research Questions ◽  
The Brain

Abstract Type 2 diabetes is associated with adverse central nervous system effects, including a doubled risk for Alzheimer’s disease (AD) and increased risk of cognitive impairment, but the mechanisms connecting diabetes to cognitive decline and dementia are unknown. One possible link between these diseases may be the associated alterations to cholesterol oxidation and metabolism in the brain. We will survey evidence demonstrating alterations to oxysterols in the brain in AD and diabetes and how these oxysterols could contribute to pathology, as well as identifying research questions that have not yet been addressed to allow for a fuller understanding of the role of oxysterols in AD and diabetes.

A-19 The Effect of Type 2 Diabetes on Attention and Executive Functioning in Mild Cognitive Impairment Patients

2021 ◽  
Vol 36 (6) ◽  
pp. 1060-1060
Author(s):  
Zachary Peart ◽  
Samantha Spagna ◽  
Bailey McDonald ◽  
Brittny Arias ◽  
D'anna Sydow ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Type 2 Diabetes ◽  
Alzheimer's Disease ◽  
Executive Functioning ◽  
Digit Span ◽  
Research Centers ◽  
Disease Research ◽  
Altered Glucose ◽  
Increased Risk

Abstract Objective To investigate the effects of Type 2 Diabetes (T2D) on performance on attention and executive function measures in a sample of MCI patients. Method Individuals with a clinician diagnosis of MCI with T2D and [n = 719,Mage = 75.24,50.3% female] and MCI persons without T2D [n = 719,Mage = 75.21,47.1% female] were selected from the Alzheimer’s Disease Research Centers database by the National Institute on Aging. Those with motor disturbances were excluded from the analysis. Significant differences (p < 0.001) were found for race and education between groups. Results Multiple ANCOVAs controlled for gender, education, age, and race on performance. Significant differences (p < 0.001) were found in performance on the Trail Making Test [A, B], Digit Span forward [longest recall, correct trials], Digit Span backward [longest recall, correct trials], and Verbal Fluency tasks [F word, L words]. No significant differences were found in the animal and vegetable naming fluency tasks. The T2D group showed poorer mean scores on every test analyzed. Conclusion Results indicated modestly lower performance on measures of attention and executive functioning in MCI patients with comorbid T2D. Previous research supports these conclusions, as T2D has been associated with increased risk for dementia, accelerated decline from MCI to dementia, and modestly lower scores on cognitive tests via effects of microvascular function and altered glucose metabolism. Future studies should aim to identify protective factors in T2D cognitive decrements while controlling for exercise, diet, SES, and underlying medical comorbidities. The NACC database is funded by NIA/NIH Grant U01 AG016976. NACC data are contributed by the NIA-funded Alzheimer’s Disease Research Centers.

scholarly journals Type 2 Diabetes Mellitus Increases The Risk of Late-Onset Alzheimer’s Disease: Ultrastructural Remodeling of the Neurovascular Unit and Diabetic Gliopathy

2019 ◽  
Vol 9 (10) ◽  
pp. 262 ◽  
Author(s):  
Hayden
Keyword(s):  
Diabetes Mellitus ◽  
Alzheimer’S Disease ◽  
Type 2 Diabetes ◽  
Alzheimer's Disease ◽  
Type 2 Diabetes Mellitus ◽  
Late Onset ◽  
Neurovascular Unit ◽  
Age Related ◽  
Increased Risk

Type 2 diabetes mellitus (T2DM) and late-onset Alzheimer’s disease–dementia (LOAD) are increasing in global prevalence and current predictions indicate they will only increase over the coming decades. These increases may be a result of the concurrent increases of obesity and aging. T2DM is associated with cognitive impairments and metabolic factors, which increase the cellular vulnerability to develop an increased risk of age-related LOAD. This review addresses possible mechanisms due to obesity, aging, multiple intersections between T2DM and LOAD and mechanisms for the continuum of progression. Multiple ultrastructural images in female diabetic db/db models are utilized to demonstrate marked cellular remodeling changes of mural and glia cells and provide for the discussion of functional changes in T2DM. Throughout this review multiple endeavors to demonstrate how T2DM increases the vulnerability of the brain’s neurovascular unit (NVU), neuroglia and neurons are presented. Five major intersecting links are considered: i. Aging (chronic age-related diseases); ii. metabolic (hyperglycemia advanced glycation end products and its receptor (AGE/RAGE) interactions and hyperinsulinemia-insulin resistance (a linking linchpin); iii. oxidative stress (reactive oxygen–nitrogen species); iv. inflammation (peripheral macrophage and central brain microglia); v. vascular (macrovascular accelerated atherosclerosis—vascular stiffening and microvascular NVU/neuroglial remodeling) with resulting impaired cerebral blood flow.

Alleles that increase risk for type 2 diabetes mellitus are not associated with increased risk for Alzheimer's disease

2014 ◽  
Vol 35 (12) ◽  
pp. 2883.e3-2883.e10 ◽  
Author(s):  
Petroula Proitsi ◽  
Michelle K. Lupton ◽  
Latha Velayudhan ◽  
Gillian Hunter ◽  
Stephen Newhouse ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Alzheimer’S Disease ◽  
Type 2 Diabetes ◽  
Alzheimer's Disease ◽  
Type 2 Diabetes Mellitus ◽  
Increased Risk ◽  
Increase Risk

scholarly journals The role of melatonin in the treatment of type 2 diabetes mellitus and Alzheimer's disease

2022 ◽  
Vol 18 (3) ◽  
pp. 983-994
Author(s):  
Shengnan Shen ◽  
Qiwen Liao ◽  
Yin Kwan Wong ◽  
Xiao Chen ◽  
Chuanbin Yang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Alzheimer’S Disease ◽  
Type 2 Diabetes ◽  
Alzheimer's Disease ◽  
Type 2 Diabetes Mellitus

scholarly journals Gut Microbiota in Alzheimer’s Disease, Depression, and Type 2 Diabetes Mellitus: The Role of Oxidative Stress

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Maria Luca ◽  
Maurizio Di Mauro ◽  
Marco Di Mauro ◽  
Antonina Luca
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Alzheimer’S Disease ◽  
Type 2 Diabetes ◽  
Alzheimer's Disease ◽  
Type 2 Diabetes Mellitus ◽  
Gut Microbiota ◽  
Therapeutic Implications

Gut microbiota consists of over 100 trillion microorganisms including at least 1000 different species of bacteria and is crucially involved in physiological and pathophysiological processes occurring in the host. An imbalanced gastrointestinal ecosystem (dysbiosis) seems to be a contributor to the development and maintenance of several diseases, such as Alzheimer’s disease, depression, and type 2 diabetes mellitus. Interestingly, the three disorders are frequently associated as demonstrated by the high comorbidity rates. In this review, we introduce gut microbiota and its role in both normal and pathological processes; then, we discuss the importance of the gut-brain axis as well as the role of oxidative stress and inflammation as mediators of the pathological processes in which dysbiosis is involved. Specific sections pertain the role of the altered gut microbiota in the pathogenesis of Alzheimer’s disease, depression, and type 2 diabetes mellitus. The therapeutic implications of microbiota manipulation are briefly discussed. Finally, a conclusion comments on the possible role of dysbiosis as a common pathogenetic contributor (via oxidative stress and inflammation) shared by the three disorders.

scholarly journals Association between the Use of Dipeptidyl Peptidase 4 Inhibitors and the Risk of Dementia among Patients with Type 2 Diabetes in Taiwan

2020 ◽  
Vol 9 (3) ◽  
pp. 660
Author(s):  
Kuan-Chan Chen ◽  
Chi-Hsiang Chung ◽  
Chieh-Hua Lu ◽  
Nian-Sheng Tzeng ◽  
Chien-Hsing Lee ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Type 2 Diabetes ◽  
Alzheimer's Disease ◽  
Vascular Dementia ◽  
Dipeptidyl Peptidase ◽  
Class Effect ◽  
Dipeptidyl Peptidase 4 ◽  
Increased Risk ◽  
Dipeptidyl Peptidase 4 Inhibitors

Study Objectives: Diabetes mellitus per se and its related therapy have been frequently associated with an increased risk of developing dementia. However, studies that explored the risk of dementia from the use of the novel oral antidiabetic medication dipeptidyl peptidase 4 inhibitor (DPP-4i) have been limited, especially in Asian populations. The present study aimed to determine the effect of DPP-4i on the subsequent risk of dementia among patients with type 2 diabetes (T2D) in Taiwan. Methods: This study utilized data from the Longitudinal Health Insurance Database between 2008 and 2015. We enrolled 2903 patients aged ≥50 years, who were on DPP-4i for a diagnosis of T2D and had no dementia. A total of 11,612 subjects were included and compared with a propensity score-matched control group who did not use DPP-4i (non-DPP-4i group). Survival analysis was performed to estimate and compare the risk of dementia—including Alzheimer’s disease, vascular dementia, and other dementia types—between the two groups. Results: Both groups had a mean age of 68 years, had a preponderance of women (61.8%), and were followed up for a mean duration of 7 years. The risk of all-cause dementia was significantly lower in the DPP-4i group than in the non-DPP-4i group (hazard ratio (HR) 0.798; 95% confidence interval (CI) 0.681–0.883; p < 0.001), with a class effect. This trend was particularly observed for vascular dementia (HR 0.575; 95% CI 0.404–0.681; p < 0.001), but not in Alzheimer’s disease (HR 0.891; 95% CI 0.712–1.265; p = 0.297). The Kaplan–Meier analysis showed that the preventive effect on dementia was positively correlated with the cumulative dose of DPP-4i. Conclusions: DPP-4i decreased the risk of dementia with a class effect, especially vascular dementia, but not in Alzheimer’s disease. Our results provide important information on the drug choice when managing patients with T2D in clinical practice.

scholarly journals A Growing Link between Circadian Rhythms, Type 2 Diabetes Mellitus and Alzheimer’s Disease

2022 ◽  
Vol 23 (1) ◽  
pp. 504
Author(s):  
Xuemin Peng ◽  
Rongping Fan ◽  
Lei Xie ◽  
Xiaoli Shi ◽  
Kun Dong ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Alzheimer’S Disease ◽  
Type 2 Diabetes ◽  
Alzheimer's Disease ◽  
Type 2 Diabetes Mellitus ◽  
Circadian Rhythm ◽  
Circadian Rhythms ◽  
Light Therapy

Type 2 diabetes mellitus (T2DM) patients are at a higher risk of developing Alzheimer’s disease (AD). Mounting evidence suggests the emerging important role of circadian rhythms in many diseases. Circadian rhythm disruption is considered to contribute to both T2DM and AD. Here, we review the relationship among circadian rhythm disruption, T2DM and AD, and suggest that the occurrence and progression of T2DM and AD may in part be associated with circadian disruption. Then, we summarize the promising therapeutic strategies targeting circadian dysfunction for T2DM and AD, including pharmacological treatment such as melatonin, orexin, and circadian molecules, as well as non-pharmacological treatments like light therapy, feeding behavior, and exercise.

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