Cited by 563Dementia and Cognitive Impairment ResearchDiabetes Treatment and ManagementNeurological Disease Mechanisms and Treatments

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Type 2 diabetes mellitus, cognitive impairment and dementia

Stewart, R., Liolitsa, D.·1999·Diabetic Medicine

DOI 10.1046/j.1464-5491.1999.00027.x

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Abstract

Summary: Aims We set out to examine the evidence for an association between cognitive impairment or dementia and the presence of Type 2 diabetes mellitus (DM). We also sought evidence of potential mechanisms for such an association. Methods A literature search of three databases was performed and the reference lists of the papers so identified were examined, using English language papers only. Results We found evidence of cross‐sectional and prospective associations between Type 2 DM and cognitive impairment, probably both for memory and executive function. There is also evidence for an elevated risk of both vascular dementia and Alzheimer’s disease in Type 2 DM albeit with strong interaction of other factors such as hypertension, dyslipidaemia and apolipoprotein E phenotype. Both vascular and non‐vascular factors are likely to play a role in dementia in diabetes. Conclusions Current classification structures for dementia may not be adequate in diabetes, where mixed pathogenesis is likely. Further research into the mechanisms of cognitive impairment in Type 2 DM may allow us to challenge the concept of dementia, at least in these patients, as an irremediable disease. Diabet. Med. 16, 93–112 (1999)

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Structural and Functional Brain Changes in Middle-Aged Type 2 Diabetic Patients: A Cross-Sectional Study
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Diabetes Is Associated with Increased Rate of Cognitive Decline in Questionably Demented Elderly
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Alterations in Hippocampal Oxidative Stress, Expression of AMPA Receptor GluR2 Subunit and Associated Spatial Memory Loss by Bacopa monnieri Extract (CDRI-08) in Streptozotocin-Induced Diabetes Mellitus Type 2 Mice
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Peripheral Inflammation and Insulin Resistance: Their Impact on Blood–Brain Barrier Integrity and Glia Activation in Alzheimer’s Disease
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“The above is strongly supported by epidemiological studies that suggest T2D is a significant risk factor for developing cognitive dysfunction and AD [47–49].”
Association Between Cognitive Function and Social Support with Glycemic Control in Adults with Diabetes Mellitus
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Effects of metabolic control, patient education and initiation of insulin therapy on the quality of life of patients with type 2 diabetes mellitus
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“9 [0–100] 71.”
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The Cause of Alzheimer’s Disease: The Theory of Multipathology Convergence to Chronic Neuronal Stress
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“Interestingly, type 2 diabetes and AD share several pathologies, including insulin resistance (see below), dysregulation of glucose and insulin signaling [159], Aβ deposition [160] and cognitive impairment [161], and mitochondrial dysfunction [162], which is the basis for some researchers to call AD “type 3 diabetes”…”
Background
Pathophysiology of cognitive dysfunction in older people with type 2 diabetes: vascular changes or neurodegeneration?
Umegaki, H. (2009) · Age and Ageing · doi:10.1093/ageing/afp211 · Cited by 63
“Moreover, recent studies have indicated that older people with T2DM have a higher risk of cognitive dysfunction or dementia [1].”
Association between diabetes and cognitive function at baseline in the Brazilian Longitudinal Study of Adult Health (ELSA- Brasil)
Teixeira, M. M., Passos, V. M. D. A., Barreto, S. M., Schmidt, M. I., Duncan, B. B., Beleigoli, A. M. R., Fonseca, M. J. M., Vidigal, P. G., Araújo, L. F., & Diniz, M. D. F. H. S. (2020) · Scientific Reports · doi:10.1038/s41598-020-58332-9 · Cited by 65
Clinical Symptoms and Risk Factors in Cerebral Microangiopathy Patients
Okroglic, S., Widmann, C. N., Urbach, H., Scheltens, P., & Heneka, M. T. (2013) · PLoS ONE · doi:10.1371/journal.pone.0053455 · Cited by 62
Moringa oleifera supplemented diet modulates nootropic-related biomolecules in the brain of STZ-induced diabetic rats treated with acarbose
Oboh, G., Oyeleye, S. I., Akintemi, O. A., & Olasehinde, T. A. (2018) · Metabolic Brain Disease · doi:10.1007/s11011-018-0198-2 · Cited by 63
“Neuropsychological studies on DM revealed impairments in cognitive function, verbal memory or complex information processing and behavioral disturbances (Stewart and Liolitsa 1999; Hasanein and Shahidi 2011).”
Background
Diabetes Mellitus in a Subgroup of Older Mexicans: Prevalence, Association with Cardiovascular Risk Factors, Functional and Cognitive Impairment, and Mortality
Rodríguez‐Saldaña, J., Morley, J. E., Reynoso, M. T. M., Medina, C. A., Salazar, P., de la Cruz, E., & Torres, A. L. N. (2002) · Journal of the American Geriatrics Society · doi:10.1046/j.1532-5415.2002.50016.x · Cited by 62
Glycogen synthase kinase-3: A potential target for diabetes
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Apolipoprotein E polymorphism in cerebrovascular & coronary heart diseases.
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Expression changes of growth-associated protein-43 (GAP-43) and mitogen-activated protein kinase phosphatase-1 (MKP-1) and in hippocampus of streptozotocin-induced diabetic cognitive impairment rats
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Neuronal Ca2+ disregulation in diabetes mellitus
Biessels, G. J., ter Laak-Poort, M., Hamers, F. P. T., & Gispen, W. H. (2002) · European Journal of Pharmacology · doi:10.1016/s0014-2999(02)01844-7 · Cited by 60
Type 2 diabetes and cognitive impairment
Strachan, M. W. J., Frier, B. M., & Deary, I. J. (2003) · Diabetic Medicine · doi:10.1046/j.1464-5491.2003.00855.x · Cited by 59
Diabetes-, stress- and ageing-related changes in synaptic plasticity in hippocampus and neocortex — The same metaplastic process?
Artola, A. (2008) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2007.11.084 · Cited by 57
Effects of Alzheimer's amyloid-beta and tau protein on mitochondrial function — role of glucose metabolism and insulin signalling
Rhein, V., & Eckert, A. (2007) · Archives of Physiology and Biochemistry · doi:10.1080/13813450701572288 · Cited by 56
“Cross-sectional studies using different large populations have shown that the percentage of type 2 diabetes among AD patients is significantly higher than among age- matched non-AD controls (Ott et al., 1996; Kuusisto et al., 1997; Stewart & Liolitsa, 1999).”
Background
Effect of tempol on the passive avoidance and novel object recognition task in diabetic rats
Jabbarpour, Z., Shahidi, ‬., Saidijam, M., Sarihi, A., Hassanzadeh, T., & Esmaeili, R. (2014) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2013.12.013 · Cited by 57
Oral supplementation of catalpol ameliorates diabetic encephalopathy in rats
Wang, C., Dan-qing, L., Xue, H., & Hu, B. (2009) · Brain Research · doi:10.1016/j.brainres.2009.10.034 · Cited by 57
“…described a series of neuropathological and neurobehavioral changes in both type 1 and type 2 diabetic subjects, such as cognitive dysfunction and decline in memory and mental speed (Awad et al., 2004; Reaven et al., 1990; Ryan et al., 1993; Stewart and Liolitsa, 1999; Strachan et al., 1997).”
Impaired neural stem/progenitor cell proliferation in streptozotocin-induced and spontaneous diabetic mice
Guo, J., Yu, C., Li, H., Liu, F., Feng, R., Wang, H., Meng, Y., Li, Z., Ju, G., & Wang, J. (2010) · Neuroscience Research · doi:10.1016/j.neures.2010.08.012 · Cited by 60
“, 2004; Biessels and Gispen, 2005) and more rarely dementia (Stewart and Liolitsa, 1999; Arvanitakis et al., 2004).”
Background
Apolipoprotein E ε4 Allele Is Associated with Vascular Dementia
Baum, L., Lam, L. C. W., Kwok, T., Lee, J., Chiu, H. F. K., Mok, V. C. T., Wong, A., Chen, X., Cheung, W. S., Pang, C. P., et al. (2006) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000095246 · Cited by 57
“Interestingly, we found an interaction between ApoE e4 and either hypertension or diabetes concerning the risk of VaD. This suggests that ApoE e4 may act primarily in concert with other risk factors and might not cause VaD if other risk factors are absent. Previous studies reported associations of diabetes or hyperten…”
Diabetes mellitus Type II and cognitive capacity in healthy aging, mild cognitive impairment and Alzheimer's disease
Degen, C., Toro, P., Schönknecht, P., Sattler, C., & Schröder, J. (2016) · Psychiatry Research · doi:10.1016/j.psychres.2016.04.009 · Cited by 56
Diabetes impairs learning performance and affects the mitochondrial function of hippocampal pyramidal neurons
Lin, Y., Wang, F., & Yang, R. (2011) · Brain Research · doi:10.1016/j.brainres.2011.07.011 · Cited by 55
Effect of pioglitazone on insulin resistance in fructose-drinking rats correlates with AGEs/RAGE inhibition and block of NAPDH oxidase and NF kappa B activation
Liu, X., Luo, D., Zheng, M., Hao, Y., Hou, L., & Zhang, S. (2009) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2009.11.059 · Cited by 55
“…epidemiological studies on cognitive impairment in patients with diabetes found evidence of crosssectional and prospective associations between type 2 diabetes and moderate degree of cognitive impairment, both for memory and executive functions (Miles and Root, 1922; Stewart and Liolitsa, 1999).”
Background
Caffeine, mood and mental performance in everyday life
Rogers, P. J. (2007) · Nutrition Bulletin · doi:10.1111/j.1467-3010.2007.00607.x · Cited by 58
Donepezil for vascular cognitive impairment
Malouf, R. S., & Birks, J. (2003) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd004395 · Cited by 54
Unraveling Alzheimer’s: Making Sense of the Relationship between Diabetes and Alzheimer’s Disease
Schilling, M. A. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-150980 · Cited by 54
“Patients treated with insulin were at the highest risk of dementia (4.3 RR) Stewart and Liolitsa, 1999 [107] 1999 Review Luchsinger et al., 2001 [48] 2001 Longitudinal cohort study Study of Black and Hispanic cohort for average of 4.3 years suggested that diabetes (baseline rate of 20”
BackgroundInfluential
Brief report: Use of the Mini-Cog as a screening tool for cognitive impairment in diabetes in primary care
Sinclair, A. J., Gadsby, R., Hillson, R., Forbes, A., & Bayer, A. J. (2013) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2013.01.001 · Cited by 52
Dementia and its associations in type 2 diabetes mellitus: The Fremantle Diabetes Study
Bruce, D. G., Harrington, N., Davis, W. A., & Davis, T. M. E. (2001) · Diabetes Research and Clinical Practice · doi:10.1016/s0168-8227(01)00266-2 · Cited by 52
Impaired Insulin Signaling and Mechanisms of Memory Loss
Bloemer, J., Bhattacharya, S., Amin, R., & Suppiramaniam, V. D. (2014) · Progress in molecular biology and translational science · doi:10.1016/b978-0-12-800101-1.00013-2 · Cited by 52
Role of Dietary and Endogenous Antioxidants in Diabetes
Marrazzo, G., Barbagallo, I. A., Galvano, F., Malaguarnera, M., Gazzolo, D., Frigiola, A., D’Orazio, N., & Volti, G. L. (2013) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2011.644874 · Cited by 51
“In addition, hyperglycaemia is unlikely to be the only factor in the development of cognitive impairments in type 2 diabetes: previous studies in patients with diabetes do not invariably show an association between chronic hyperglycaemia, as assessed by HbA1 levels, and the severity of cognitive impairments (Strachan…”
Background
Beneficial Effects ofTeucrium poliumand Metformin on Diabetes-Induced Memory Impairments and Brain Tissue Oxidative Damage in Rats
Mousavi, S. M., Niazmand, S., Hosseini, M., Hassanzadeh, Z., Sadeghnia, H. R., Vafaee, F., & Keshavarzi, Z. (2015) · International Journal of Alzheimer s Disease · doi:10.1155/2015/493729 · Cited by 51
“Beneficial Effects of Teucrium polium and Metformin on”
Background
Cognitive and Physical Disabilities and Aging-Related Complications of Diabetes
Gregg, E. W., & Brown, A. F. (2003) · Clinical Diabetes · doi:10.2337/diaclin.21.3.113 · Cited by 51

Authors: Stewart, R., & Liolitsa, D.
Corresponding author: Stewart, R.
ORCID: Stewart, R.
Venue: Diabetic Medicine
Publisher: Wiley
Published: 1999-02
Volume: 16
Issue: 2
Pages: 93-112
ISSN: 0742-3071 (ISSN-L)
1464-5491
DOI: 10.1046/j.1464-5491.1999.00027.x
OpenAlex: W2078868323
Cited by: 562
References: 145
Citations by year: 2026: 2 · 2025: 12 · 2024: 13 · 2023: 11 · 2022: 12 · 2021: 12 · 2020: 18 · 2019: 18 · 2018: 18 · 2017: 18 · 2016: 19 · 2015: 33 · 2014: 17 · 2013: 21 · 2012: 35
FWCI: 9.03
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor, 1057 d)
Locations: Diabetic Medicine (publishedVersion)
PubMed (publishedVersion)
Funders: Wellcome Trust
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
Keywords: type 2 diabetes, cognitive impairment, dementia, vascular dementia, Alzheimer's disease, memory, executive function, hypertension, dyslipidemia, apolipoprotein E, dementia classification
MeSH terms: Cognition Disorders, Cross-Sectional Studies, Dementia, Diabetes Mellitus, Type 2, Humans, Population Surveillance, Prospective Studies, Risk Factors, Case-Control Studies

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Type 2 diabetes mellitus, cognitive impairment and dementia

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