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Alzheimer Disease l: Introduction01:29

Alzheimer Disease l: Introduction

Alzheimer disease is a chronic, progressive, and irreversible neurodegenerative disorder and the most common cause of dementia in older adults. It leads to gradual neuronal loss, causing cognitive decline, behavioral changes, and loss of functional independence.Risk Factors and EtiologyThe disease is multifactorial. Age is the strongest risk factor, with prevalence doubling every 5 years after age 65. Genetic factors include mutations in genes such as APP, PSEN1, and PSEN2, which are associated...
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Chronic stress has been linked to both the onset and progression of serious health conditions, including Type 2 diabetes and cancer. Type 2 diabetes, a widespread chronic illness, is closely associated with obesity and insulin resistance, both of which often worsen under stress. Studies indicate that men experiencing high levels of chronic stress face a 45% higher risk of developing diabetes compared to those with minimal stress. Stress triggers physiological responses that elevate blood...
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Dementia is an acquired, progressive syndrome characterized by a decline in multiple cognitive domains severe enough to impair daily functioning and reduce independence. Although memory loss is a central feature, the diagnosis requires additional deficits involving language, executive function, visuospatial skills, judgment, calculation, or abstract reasoning. These cognitive impairments reflect underlying neurodegenerative or vascular processes that gradually disrupt neuronal networks...
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For most patients, experiencing several weeks of polyuria, polydipsia, fatigue, and significant weight loss may indicate the presence of diabetes. Furthermore, adults displaying the phenotypic appearance of type 2 diabetes (particularly those who are obese and not initially insulin-requiring), may have islet cell autoantibodies, suggesting autoimmune-mediated β cell destruction and a diagnosis of latent autoimmune diabetes of adults (LADA). The categorization of glucose homeostasis is based on...
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Osmotic Minipump Implantation for Increasing Glucose Concentration in Mouse Cerebrospinal Fluid
06:21

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Published on: April 7, 2023

(Pre)diabetes, brain aging, and cognition.

Jarbas S Roriz-Filho1, Ticiana M Sá-Roriz, Idiane Rosset

  • 1Division of Geriatrics, Department of Internal Medicine, Faculty of Medicine, University of São Paulo-RP, Brazil.

Biochimica Et Biophysica Acta
|January 13, 2009
PubMed
Summary
This summary is machine-generated.

Diabetes and insulin resistance are linked to cognitive decline and dementia. High insulin levels may impair amyloid-beta clearance, accelerating brain aging and increasing dementia risk.

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Area of Science:

  • Neuroscience
  • Endocrinology
  • Gerontology

Background:

  • Diabetes mellitus (DM) and related metabolic phenotypes (obesity, metabolic syndrome) are increasingly recognized as risk factors for cognitive dysfunction and dementia, including Alzheimer's disease (AD).
  • Both Type 1 and Type 2 diabetes negatively impact neuropsychological functions.
  • Chronic hyperglycemia and hyperinsulinemia contribute to oxidative stress and advanced glycation end-products (AGEs), key mechanisms in aging and potentially AD pathogenesis.

Purpose of the Study:

  • To explore the paradoxical relationship between insulin's neurotrophic role and its risk factor status in AD.
  • To elucidate the mechanisms by which insulin resistance, hyperglycemia, and hyperinsulinemia contribute to cognitive decline and dementia.

Main Methods:

  • Review of existing literature on diabetes, insulin homeostasis, and cognitive function.
  • Analysis of the role of insulin-degrading enzyme (IDE) in amyloid-beta (Abeta) clearance.
  • Examination of the impact of hyperglycemia and hyperinsulinemia on brain aging markers like tau hyperphosphorylation, amyloid oligomerization, and microangiopathy.

Main Results:

  • Insulin, while neurotrophic at normal levels, can impede Abeta clearance in conditions of hyperinsulinemia due to competition for IDE.
  • Hyperglycemia and hyperinsulinemia accelerate brain aging through mechanisms including tau hyperphosphorylation, amyloid oligomerization, and microangiopathy.
  • Diabetes is associated with increased leukoaraiosis (White Matter High-Intensity Lesions - WMHL), a marker linked to cognitive impairment and dementia risk.

Conclusions:

  • Insulin resistance phenotypes represent significant risk factors for cognitive decline and dementia.
  • Impaired Abeta clearance due to hyperinsulinemia and IDE competition is a potential mechanism linking diabetes to AD.
  • Diabetes-associated brain aging, including microangiopathy and WMHL, contributes to cognitive dysfunction and dementia.