Alzheimer’s Disease as Type 3 Diabetes: Common Pathophysiological Mechanisms between Alzheimer’s Disease and Type 2 Diabetes

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(5), P. 2687 - 2687

Published: Feb. 28, 2022

Globally, the incidence of type 2 diabetes mellitus (T2DM) and Alzheimer’s disease (AD) epidemics is increasing rapidly has huge financial emotional costs. The purpose current review article to discuss shared pathophysiological connections between AD T2DM. Research findings are presented underline vital role that insulin plays in brain’s neurotransmitters, homeostasis energy, as well memory capacity. this indicate existence a mechanistic interplay pathogenesis with T2DM and, especially, disrupted signaling. interlinked resistance, neuroinflammation, oxidative stress, advanced glycosylation end products (AGEs), mitochondrial dysfunction metabolic syndrome. Beta-amyloid, tau protein amylin can accumulate brains. Given patients not routinely evaluated terms their cognitive status, they rarely treated for impairment. Similarly, high levels or Studies suggesting caused by resistance brain also offer strong support hypothesis 3 diabetes.

Language: Английский

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Metformin Use Is Associated With Slowed Cognitive Decline and Reduced Incident Dementia in Older Adults With Type 2 Diabetes: The Sydney Memory and Ageing Study

Diabetes Care, Journal Year: 2020, Volume and Issue: 43(11), P. 2691 - 2701

Published: Sept. 23, 2020

OBJECTIVE Type 2 diabetes (diabetes) is characterized by accelerated cognitive decline and higher dementia risk. Controversy exists regarding the impact of metformin, which associated with both increased decreased rates. The objective this study was to determine association metformin use incident over 6 years in participants compared those not receiving without diabetes. RESEARCH DESIGN AND METHODS A prospective observational conducted N = 1,037 community-dwelling older aged 70–90 at baseline (the Sydney Memory Ageing Study). Exclusion criteria were dementia, major neurological or psychiatric disease, progressive malignancy. Neuropsychological testing measured function every years; a battery tests executive function, memory, attention/speed, language, visuospatial individually. These used measure global cognition. Incident ascertained multidisciplinary panel. Total brain, hippocampal, parahippocampal volumes MRI (n 526). Data analyzed linear mixed modeling, including covariates age, sex, education, BMI, heart hypertension, stroke, smoking, apolipoprotein Eε4 carriage. RESULTS Of n 1,037, 123 had diabetes; 67 received (DM+MF) demographically similar who did (DM-noMF) (no-DM). DM+MF significantly slower cognition DM-noMF. DM-noMF (odds ratio 5.29 [95% CI 1.17–23.88]; P 0.05). CONCLUSIONS Older people have lower Large randomized studies will whether these associations can be attributed metformin.

Language: Английский

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Glucose, glycolysis, and neurodegenerative diseases

Journal of Cellular Physiology, Journal Year: 2020, Volume and Issue: 235(11), P. 7653 - 7662

Published: April 2, 2020

Abstract Prolonged survival of a typical postmitotic neuron hinges on balance between multiple processes, among these are sustenance ATP production and protection against reactive oxygen species. In neuropathological conditions, mitochondrial defects often lead to both drop in levels, as well increase species from inefficient electron transport processes NADPH‐oxidases activities. The former resulted the phenomenon compensatory aerobic glycolysis. latter stretches capacity cell's redox buffering capacity, may damages key enzymes involved energy metabolism. Several recent reports have indicated that enhancing glucose availability uptake, increasing glycolytic flux via pharmacological or genetic manipulation enzymes, could be protective animal models several major neurodegenerative diseases, including Parkinson's disease, Huntington's Amyotrophic lateral sclerosis. Activation canonical Wnt signaling, which improves disease symptoms mouse Alzheimer's also appears work an elevation enhance Here, I discuss findings possible underlying mechanisms how uptake glycolysis neuroprotective. Increased would help alleviate deficiency, ATP's hydrotropic effect solubility clearance toxic aggregates prevalent many diseases. Furthermore, channeling into Pentose Phosphate Pathway cell.

Language: Английский

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Altered glucose metabolism in Alzheimer's disease: Role of mitochondrial dysfunction and oxidative stress

Free Radical Biology and Medicine, Journal Year: 2022, Volume and Issue: 193, P. 134 - 157

Published: Oct. 4, 2022

Language: Английский

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Impairment of insulin signaling pathway PI3K/Akt/mTOR and insulin resistance induced AGEs on diabetes mellitus and neurodegenerative diseases: a perspective review

Molecular and Cellular Biochemistry, Journal Year: 2022, Volume and Issue: 478(6), P. 1307 - 1324

Published: Oct. 29, 2022

Language: Английский

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Associations Between Diabetes Mellitus and Neurodegenerative Diseases

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(2), P. 542 - 542

Published: Jan. 10, 2025

Diabetes mellitus (DM) and neurodegenerative diseases/disturbances are worldwide health problems. The most common chronic conditions diagnosed in persons 60 years older type 2 diabetes (T2DM) cognitive impairment. It was found that is a major risk for decline, dementia, Parkinson's disease (PD), Alzheimer's (AD), Huntington's (HD), amyotrophic lateral sclerosis (ALS) other disorders. Different mechanisms of associations between these diseases have been suggested. For example, it postulated an impaired intracellular insulin signaling pathway, together with hyperglycemia hyperinsulinemia, may cause pathological changes, such as dysfunction the mitochondria, oxidative stress inflammatory responses, etc. association diseases, well associations, needs further investigation. aim this review to describe mellitus, especially 1 (T1DM) selected i.e., disease, sclerosis. Suggested also described.

Language: Английский

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Metabolism: A Novel Shared Link between Diabetes Mellitus and Alzheimer’s Disease

Journal of Diabetes Research, Journal Year: 2020, Volume and Issue: 2020, P. 1 - 12

Published: Jan. 30, 2020

As a chronic metabolic disease, diabetes mellitus (DM) is broadly characterized by elevated levels of blood glucose. Novel epidemiological studies demonstrate that some diabetic patients have an increased risk developing dementia compared with healthy individuals. Alzheimer’s disease (AD) the most frequent cause and leads to major progressive deficits in memory cognitive function. Multiple identified for AD populations, but it still unclear which will develop biological characteristics can predict decline. Although few mechanistic shown clear pathophysiological links between DM AD, there are several plausible ways this may occur. Since has many common impaired insulin signaling pathways, be regarded as disease. We conclude from published literature body’s status under certain circumstances such abnormalities increase incidence affecting glucose transport brain reducing metabolism. Furthermore, due its plentiful lipid content high energy requirement, brain’s metabolism places great demands on mitochondria. Thus, more susceptible oxidative damage than rest body. Emerging evidence suggests both stress mitochondrial dysfunction related amyloid- β (A ) pathology. Protein changes unfolded protein response or endoplasmic reticulum regulate A production closely associated tau Altogether, disorders including glucose/lipid metabolism, stress, dysfunction, caused signal pathway. These factors could prevalence via promotion

Language: Английский

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A Review and Hypothesized Model of the Mechanisms That Underpin the Relationship Between Inflammation and Cognition in the Elderly

Frontiers in Aging Neuroscience, Journal Year: 2019, Volume and Issue: 11

Published: March 13, 2019

Age is associated with increased risk for several disorders including dementias, cardiovascular disease, atherosclerosis, obesity, and diabetes. also cognitive decline particularly in domains memory processing speed. With increasing life expectancies many countries, the number of people experiencing age-associated impairment therefore from both economic social terms amelioration or slowing ageing an important target future research. However, biological causes age are not yet well understood. In current review, we outline role inflammation describe inflammatory processes, which have a direct effect on brain function indirect effects via changes function.

Language: Английский

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Insulin Resistance at the Crossroad of Alzheimer Disease Pathology: A Review

Frontiers in Endocrinology, Journal Year: 2020, Volume and Issue: 11

Published: Nov. 5, 2020

Insulin plays a major neuroprotective and trophic function for cerebral cells population, thus countering apoptosis, beta amyloid toxicity, oxidative stress; favoring neuronal survival, enhancing memory learning processes. resistance impaired glucose metabolism are invariantly reported in Alzheimer's disease (AD) other neurodegenerative AD is fatal disorder which progressive hypometabolism parallels to cognitive impairment. Although may appear progress virtue of multifactorial nosogenic ingredients, multiple interperpetuative interconnected vicious circles drive pathophysiology. The primarily metabolic/energetic accumulation as by-product more proximal events. As bridge between type-2 diabetes, activation c-Jun N-terminal kinase (JNK) pathway with the ensued serine phosphorylation IRS-1/2 be at crossroads insulin its subsequent dysmetabolic consequences. Central axis bankruptcy translates vulnerability demise. link chain pathogenic circles, mitochondrial dysfunction, stress, peripheral/central immune-inflammation increasingly advocated pathology drivers. Pharmacological interventions addressed preserve biogenesis, integral functionality mitophagy diseased organelles attenuate adjacent spillover free radicals that further perpetuate damages catalyzes inflammation. / or peripheral inflammation account local flood pro-inflammatory cytokines along astroglyosis amplifies resistance, stress. All these elements endogenous stressor factors contribute JNK activation. Taken together, evidences incite identify novel multi-mechanistic approaches succeed ameliorating this pandemic affliction.

Language: Английский

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Type 2 Diabetes Mellitus as a Risk Factor for Alzheimer’s Disease: Review and Meta-Analysis

Biomedicines, Journal Year: 2022, Volume and Issue: 10(4), P. 778 - 778

Published: March 27, 2022

Alzheimer’s disease is the most common type of dementia, reaching 60–80% case totals, and one major global causes elderly population’s decline in functionality concerning daily life activities. Epidemiological research has already indicated that, addition to several others metabolic factors, diabetes mellitus 2 a risk factor disease. Many molecular pathways have been described, at same time, there are clues that suggest connection between disease, through specific genes, autophagy, even inflammatory pathways. A systematic review with meta-analysis was conducted, its main goal reveal multilevel these diseases.

Language: Английский

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