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Emerging links between type 2 diabetes and Alzheimer's disease
Open accessAbstract
Type 2 diabetes mellitus and Alzheimer's disease are both associated with increasing age, and each increases the risk of development of the other. Epidemiological, clinical, biochemical and imaging studies have shown that elevated glucose levels and diabetes are associated with cognitive dysfunction, the most prevalent cause of which is Alzheimer's disease. Cross sectional studies have clearly shown such an association, whereas longitudinal studies are equivocal, reflecting the many complex ways in which the two interact. Despite the dichotomy, common risk and etiological factors (obesity, dyslipidemia, insulin resistance, and sedentary habits) are recognized; correction of these by lifestyle changes and pharmacological agents can be expected to prevent or retard the progression of both diseases. Common pathogenic factors in both conditions span a broad sweep including chronic hyperglycemia per se, hyperinsulinemia, insulin resistance, acute hypoglycemic episodes, especially in the elderly, microvascular disease, fibrillar deposits (in brain in Alzheimer's disease and in pancreas in type 2 diabetes), altered insulin processing, inflammation, obesity, dyslipidemia, altered levels of insulin like growth factor and occurrence of variant forms of the protein butyrylcholinesterase. Of interest not only do lifestyle measures have a protective effect against the development of cognitive impairment due to Alzheimer's disease, but so do some of the pharmacological agents used in the treatment of diabetes such as insulin (especially when delivered intranasally), metformin, peroxisome proliferator-activated receptors γ agonists, glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors. Diabetes must be recognized as a risk for development of Alzheimer's disease; clinicians must ensure preventive care be given to control and postpone both conditions, and to identify cognitive impairment early to manage it appropriately.
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“AD patients are predisposed to some complications including increased oxidative stress (Sultana et al., 2011), morbidity, mortality (Schelke et al., 2016), microvascular disease, dyslipidemia, and insulin resistance (Sridhar et al., 2015).”
From Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer's Disease: A Randomized, Double-Blind and Controlled Trial (2016) · cites this paper as Sridhar et al., 2015
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Diabetes Mellitus and Cognitive Decline – Prevention Should Not Be Delayed!
Sinclair, A. J., & Vellas, B. J. (2018) · The Journal of Prevention of Alzheimer s Disease · doi:10.14283/jpad.2018.9 · Cited by 6
“The pathophysiological basis remains uncertain but multiple factors are likely to play a part (21)including the hyperglycaemic state itself, hypoglycaemia, impaired neuroregulatory aspects of insulin action (leading to dysregulation of Aβ amyloid peptide, inflammation, modulating neurotransmitter…”
Zhang, Y., Deng, S., Zhong, H., Liu, M., Ding, J., Geng, R., & Tu, Q. (2023) · Biomedicines · doi:10.3390/biomedicines11040993 · Cited by 6
“Furthermore, patients with T2DM generally show worse cognitive performance [10] and a higher risk of dementia [11,12].”
BackgroundYesudas, C., Neethu, P., & Devaraj, I. (2024) · Brain Disorders · doi:10.1016/j.dscb.2024.100178 · Cited by 4
The neurogenic effects of rosmarinic acid in a mouse model of type 2 diabetes mellitus
Ali, M., & Zahid, S. (2020) · Brazilian Journal of Pharmaceutical Sciences · doi:10.1590/s2175-979020200003180772 · Cited by 4
Multi-nutrient interventions and cognitive ageing: are we barking up the right tree?
Young, H. A., Geurts, L., Scarmeas, N., Benton, D., Brennan, L., Farrimond, J. A., Kiliaan, A. J., Pooler, A. M., Trovò, L., Sijben, J., et al. (2022) · Nutrition Research Reviews · doi:10.1017/s095442242200018x · Cited by 4
“For example, it was reported that type II diabetes is a risk factor for developing AD (50,51) .”
BackgroundCognitive Impairment and the Diabetic Brain
Jellinger, K. A. (2015) · International Journal of Neurology and Neurotherapy · doi:10.23937/2378-3001/2/2/1033 · Cited by 4
“Intranasal administration of insulin successfully improved memory deficits without the risk of peripheral hypoglycaemia in AD patients [20,73,101,102].”
InfluentialEffects of long-term exposure to aluminum in the hippocampus in the type 2 diabetes model rats
Nam, S. M., Yoo, D. Y., Kwon, H. J., Kim, J. W., Jung, H. Y., Kim, D. W., Seong, J. K., Hwang, I. K., & Yoon, Y. S. (2018) · Toxicology Research · doi:10.1039/c8tx00192h · Cited by 4
Wybrane zagadnienia z zakresu przemysłu spożywczego oraz zarządzania i inżynierii produkcji
Babicz, M., & Kropiwiec-Domańska, K. (2020) · doi:10.24326/mon.2020.5 · Cited by 4
Zhang, H., Zhou, G., Li, C., Muhammad, M., Yang, S., Xie, J., & Kang, X. (2025) · Medicine Bulletin · doi:10.1002/mdb2.70017 · Cited by 3
C-peptide: an essential ally in microvascular complications of type 2 diabetes mellitus and obesity
Esze, R., Barna, S., Fülöp, P., Kempler, P., Mikó, M., Páll, D., Paragh, G., Somodi, S., Emri, M., Képes, Z., et al. (2024) · Diabetology & Metabolic Syndrome · doi:10.1186/s13098-024-01454-1 · Cited by 3
“Cerebral microvascular impairments induced by metabolic dysfunction lead to perfusion abnormalities that represent an increased likelihood for the development of cognitive dysfunction and neurodegenerative disorders [4–8].”
BackgroundAdipobiology of the brain: From brain diabetes to adipose Alzheimer‘s disease
Aloe, L., Tonchev, A. B., Maucher, A., Fiore, M., Zhelezov, M., & Chaldakov, G. N. (2015) · Adipobiology · doi:10.14748/adipo.v7.1559 · Cited by 3
“brain-metabolism link (36-55) the concept of cognitive diabetes and brain diabetes was recently introduced (56, 57; for the antidiabetic drug metformin and APP processing, see 58, 59).”
BackgroundSridhar, G. R. (2017) · SpringerBriefs in applied sciences and technology · doi:10.1007/978-981-10-6653-5_4 · Cited by 3
Self-citationPrediction of Alzheimer Disease Using Pearson Recursive Graph Convolutional Neural NetworkPreprint
Roobini, M. S., & Lakshmi, M. (2021) · Research Square · doi:10.21203/rs.3.rs-935323/v1 · Cited by 3
“Recent research proves that there is a relation between the type 2 diabetes and AD [8].”
BackgroundSong, B., Yue, D., Yan, H., Feng, L., & Li, M. (2025) · Drug Design Development and Therapy · doi:10.2147/dddt.s531909 · Cited by 3
“9,10 AD can be considered a central metabolic disorder characterized by impaired glucose metabolism, which is associated with compromised insulin and IGF (insulin-like growth factor) signaling pathways in the brain.”
Salam, A., Mukherjee, B., Sapkal, G. T., & Nandi, C. K. (2025) · Chemical & Biomedical Imaging · doi:10.1021/cbmi.5c00170 · Cited by 2
“38,39 Therefore, the Zn − Sl − MPM complex was incubated in cells for real-time tracking of lysosomes to effectively monitor the change in microviscosity of lysosomes within a hyperglycemic environment.”
Serum levels of acetylcholinesterase in metabolic syndrome
Hristova, M. G. (2015) · Adipobiology · doi:10.14748/adipo.v7.1561 · Cited by 2
“(14, 15) and since NGF and BDNF are also implicated in the pathogenesis of cardiometabolic and neurodegenerative diseases (16, 17), further studies are required on the possible role of NGF/BDNF and acetylcholinesterase/CRP in the development of these diseases.”
BackgroundDiabetes and data in many forms
Sridhar, G. R. (2016) · International Journal of Diabetes in Developing Countries · doi:10.1007/s13410-016-0540-3 · Cited by 2
“A series of other studies have suggested that it could be one of the mediators between type 2 diabetes mellitus and Alzheimer’s disease [39].”
BackgroundSelf-citationMurali, P., Venkatasubramanian, V., & Ram, B. (2020) · Sugar and Sugar Derivatives: Changing Consumer Preferences · doi:10.1007/978-981-15-6663-9_16 · Cited by 2
НЕЙРОПРОТЕКТОРНІ ВЛАСТИВОСТІ α-ЛІПОЄВОЇ КИСЛОТИ У ХВОРИХ НА ДІАБЕТ
SOKOLOVA, L. K., Vm, P., & Tronko, M. D. (2021) · PROBLEMS OF ENDOCRINE PATHOLOGY · doi:10.21856/j-pep.2021.4.19 · Cited by 2
Choi, Y., Song, J. E., Kim, E., Kim, C. H., Lee, J. E., & Song, H. (2023) · Yonsei Medical Journal · doi:10.3349/ymj.2022.0554 · Cited by 2
“An epidemiological study reported the frequency of dementia in patients among diabetic patients.(1) Since type 2 diabetes mellitus Hyperpolarized [1-(13)C]pyruvate Magnetic Resonance Spectroscopy Shows That Agmatine Increased Lactate Production in the Brain of Type 2 Diabetic Mice”
BackgroundMeng, Y., Lu, J., Shi, C., Zhu, H., & Zhang, J. (2025) · Diabetology & Metabolic Syndrome · doi:10.1186/s13098-025-01876-5 · Cited by 1
“Apart from its well-known vascular and metabolic complications, T2DM is increasingly recognized as a significant risk factor for cognitive decline and dementia, including Alzheimer’s disease (AD) and vascular cognitive impairment (VCI) [1].”
van Ginneken, V., de Vries, E., Verheij, E. R., & van der Greef, J. (2017) · Journal of Bioanalysis & Biomedicine · doi:10.4172/1948-593x.1000171 · Cited by 1
FONKSİYONEL GIDA BİLEŞENLERİNİN BİLİŞSEL FONKSİYONLAR ÜZERİNE MOLEKÜLER ETKİ MEKANİZMALARI
Güzel‐Seydim, Z. B., Keles, S., & Şatır, G. (2024) · JOURNAL OF BIOTECHNOLOGY AND STRATEGIC HEALTH RESEARCH · doi:10.34084/bshr.1413281 · Cited by 1
Amylin and amylin receptors in Alzheimer's disease
Fu, W., & Jhamandas, J. H. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-815868-5.00020-7 · Cited by 1
Fernandez-Filha, A. H. (2017) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/d.89.2017.tde-09022017-142711 · Cited by 1
Wei, B., Stitt, A. W., & Little, K. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.10.24.684393 · Cited by 1
Metadata
- Authors
- Sridhar, G. R.
- Corresponding author
- Sridhar, Gumpeny R
- ORCID
- Sridhar, Gumpeny R
- Venue
- World Journal of Diabetes
- Publisher
- Baishideng Publishing Group Inc.
- Published
- 2015
- Volume
- 6
- Issue
- 5
- Pages
- 744
- ISSN
- 1948-9358 (ISSN-L)
- PMC
- PMC4458503
- OpenAlex
- W563315964
- Cited by
- 123
- References
- 65
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 5 · 2023: 8 · 2022: 19 · 2021: 7 · 2020: 14 · 2019: 14 · 2018: 11 · 2017: 12 · 2016: 13 · 2015: 8
- FWCI
- 2.02
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- cc-by-nc
- Locations
- World Journal of Diabetes (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- type 2 diabetes, Alzheimer's disease, cognitive impairment, hyperglycemia, insulin resistance, hyperinsulinemia, obesity, dyslipidemia, sedentary lifestyle, insulin-like growth factor, butyrylcholinesterase, insulin therapy, metformin, PPARγ agonists, GLP-1 receptor agonists, DPP-4 inhibitors, dementia prevention
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