Clinical antidiabetic medication used in Alzheimer’s disease: From basic discovery to therapeutics development

Huang, Juan; Huang, Nanqu; Cui, Di; Shi, Jingshan; Qiu, Yu

doi:10.3389/fnagi.2023.1122300

Cited by 5 publications

(3 citation statements)

References 78 publications

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“…Self-reported balance difficulty and dizziness was subsequently linked to worse concentration ability and increased confusion (48). The Alzheimer's-related degeneration that most affects vestibular processing occurs in cortical regions responsible for visuospatial processing (50). However, deficits in the vestibular system may precede, and indeed may cause, neurodegeneration in these visuospatial domains (51,52).…”

Section: Discussionmentioning

confidence: 99%

Epidemiology and Comorbidities of Vestibular Disorders: Preliminary Findings of the AVOCADO Study

Thorman,

Schrack,

Schubert

2024

Otol Neurotol

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Introduction Studies on incidence and prevalence of vestibular disorders tend to focus on small pockets of patients recruited from specialized clinics and often exclude measures of vestibular function. The objectives of the study were to characterize patients with common vestibular disorders, estimate the prevalence of common vestibular disorders, and ascertain whether patients with vestibular disorders experience increased risks of falls and morbidity. Materials and Methods This retrospective cohort study includes both inpatient and outpatient routine clinical care data culled from a nationally representative, population-based sample. Patients were included if their record in the TriNetX Diamond Cohort comprised at least one vestibular function test or vestibular diagnosis. The main outcome measures were diagnosis with a vestibular disorder, a fall, or a common medical comorbidity (e.g., diabetes, cerebrovascular disease). Results The cohort includes n = 4,575,724 patients, of which 55% (n = 2,497,136) had a minimum of one vestibular diagnosis. Patients with vestibular diagnoses were 61.3 ± 16.6 years old (mean ± standard deviation), 67% women, 28% White race (69% unknown race), and 30% of non-Hispanic or Latino ethnicity (66% unknown ethnicity). The prevalence of vestibular disorders was estimated at 2.98% (95% confidence interval [CI]: 2.98–2.98%). Patients with vestibular diagnoses experienced a significantly greater odds of falls (odds ratio [OR] = 1.04; 95% CI: 1.02–1.05), cerebrovascular disease (OR = 1.42; 95% CI: 1.40–1.43), ischemic heart disease (OR = 1.17; 95% CI: 1.16–1.19), and diabetes (OR = 1.14; 95% CI: 1.13–1.15), among others. Discussion Vestibular disorders affect an estimated 3% of the U.S. population, after weighting. Patients with these disorders are at greater risk for many common, consequential medical conditions.

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Section: Discussionmentioning

confidence: 99%

Epidemiology and Comorbidities of Vestibular Disorders: Preliminary Findings of the AVOCADO Study

Thorman,

Schrack,

Schubert

2024

Otol Neurotol

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“…In elderly individuals, falls resulting from hypoglycemia can have severe consequences, and patients should be advised to use these medications only when there is strong evidence of benefit for dementia. Future studies in the design of such drugs should consider the mechanism of such drugs, such as regulating the insulin pathway, having minimal effect on blood glucose (or stabilizing blood glucose within a reasonable range) (Huang et al, 2023).…”

Section: Potential Directionsmentioning

confidence: 99%

Novel targets and therapies of metformin in dementia: old drug, new insights

Cui,

Lv,

Geng

et al. 2024

Front. Pharmacol.

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Dementia is a devastating disorder characterized by progressive and persistent cognitive decline, imposing a heavy public health burden on the individual and society. Despite numerous efforts by researchers in the field of dementia, pharmacological treatments are limited to relieving symptoms and fail to prevent disease progression. Therefore, studies exploring novel therapeutics or repurposing classical drugs indicated for other diseases are urgently needed. Metformin, a first-line antihyperglycemic drug used to treat type 2 diabetes, has been shown to be beneficial in neurodegenerative diseases including dementia. This review discusses and evaluates the neuroprotective role of metformin in dementia, from the perspective of basic and clinical studies. Mechanistically, metformin has been shown to improve insulin resistance, reduce neuronal apoptosis, and decrease oxidative stress and neuroinflammation in the brain. Collectively, the current data presented here support the future potential of metformin as a potential therapeutic strategy for dementia. This study also inspires a new field for future translational studies and clinical research to discover novel therapeutic targets for dementia.

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“…While certain studies have demonstrated favorable results, contrasting outcomes marked by the absence of noteworthy effects or conflicting findings have also been reported. These inconsistencies could potentially be elucidated by disparities in multiple factors, including study architecture, specific patient demographics, variations in drug protocols, and the diverse array of metrics employed to gauge outcomes [56][57][58][59][60][61][62].…”

Section: Clinical Studies Investigating the Use Of Antidiabetic Agent...mentioning

confidence: 99%

Exploring the Potential of Antidiabetic Agents as Therapeutic Approaches for Alzheimer's and Parkinson's Diseases: A Comprehensive Review

Koshatwar,

Acharya,

Prasad

et al. 2023

Cureus

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Alzheimer's and Parkinson's are two prevalent neurodegenerative disorders with significant societal and healthcare burdens. The search for effective therapeutic approaches to combat these diseases has led to growing interest in exploring the potential of antidiabetic agents. This comprehensive review aims to provide a detailed overview of the current literature on using antidiabetic agents as therapeutic interventions for Alzheimer's and Parkinson's diseases. We discuss the underlying pathological mechanisms of these neurodegenerative diseases, including protein misfolding, inflammation, oxidative stress, and mitochondrial dysfunction. We then delve into the potential mechanisms by which antidiabetic agents may exert neuroprotective effects, including regulation of glucose metabolism and insulin signaling, antiinflammatory effects, modulation of oxidative stress, and improvement of mitochondrial function and bioenergetics. We highlight in vitro, animal, and clinical studies that support the potential benefits of antidiabetic agents in reducing disease pathology and improving clinical outcomes. However, we also acknowledge these agents' limitations, variability in treatment response, and potential side effects. Furthermore, we explore emerging therapeutic targets and novel approaches, such as glucagon-like peptide-1 receptor (GLP-1R) agonists, insulin sensitizer drugs, neuroinflammation-targeted therapies, and precision medicine approaches. The review concludes by emphasizing the need for further research, including largescale clinical trials, to validate the efficacy and safety of antidiabetic agents in treating Alzheimer's and Parkinson's disease. The collaboration between researchers, clinicians, and pharmaceutical companies is essential in advancing the field and effectively treating patients affected by these debilitating neurodegenerative disorders.

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Clinical antidiabetic medication used in Alzheimer’s disease: From basic discovery to therapeutics development

Cited by 5 publications

References 78 publications

Epidemiology and Comorbidities of Vestibular Disorders: Preliminary Findings of the AVOCADO Study

Epidemiology and Comorbidities of Vestibular Disorders: Preliminary Findings of the AVOCADO Study

Novel targets and therapies of metformin in dementia: old drug, new insights

Exploring the Potential of Antidiabetic Agents as Therapeutic Approaches for Alzheimer's and Parkinson's Diseases: A Comprehensive Review

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