The DOI matches its Crossref record; 145 of the 145 references it cites were found in a registry or an index.
Type 2 diabetes mellitus, cognitive impairment and dementia
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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“There is a growing literature indicating that individuals with diabetes have impairments in recent memory (3–6).”
From Reduced glucose tolerance is associated with poor memory performance and hippocampal atrophy among normal elderly (2003) · cites this paper as [4]
In the citing paper
“However, many of these studies were cross-sectional and were thus unable to provide estimates of diabetes as a risk factor for future cognitive dysfunction.”
From Cognitive decline and dementia in diabetes—systematic overview of prospective observational studies (2005) · cites this paper as [6]
In the citing paper
“Recent evidence from several epidemiological studies suggests that it is also a risk factor for cognitive dysfunction [3 -6].”
From Cognitive decline and dementia in diabetes—systematic overview of prospective observational studies (2005) · cites this paper as [6]
In the citing paper
“Indeed, only one [7] of the review articles that summarised the available data pertaining to this relationship [4, 6 -11] provided a quantitative estimate.”
From Cognitive decline and dementia in diabetes—systematic overview of prospective observational studies (2005) · cites this paper as [6]
In the citing paper
“These findings are supported by previous reviews of the available longitudinal studies [3, 4, 6].”
From Cognitive decline and dementia in diabetes—systematic overview of prospective observational studies (2005) · cites this paper as [6]
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Diabetes, Insulin and Alzheimer's Disease
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“Recent studies have shown that patients with T2DM have a higher risk of developing cognitive impairment and are prone to dementia (Ott et al., 1999; Stewart and Liolitsa, 1999; Exalto et al., 2012; Pearce et al., 2012).”
BackgroundBafadam, S., Beheshti, F., Khodabakhshi, T., Asghari, A., Ebrahimi, B., Sadeghnia, H. R., Mahmoudabady, M., Niazmand, S., & Hosseini, M. (2019) · Hormone Molecular Biology and Clinical Investigation · doi:10.1515/hmbci-2018-0074 · Cited by 24
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“By contrast, insulin resistance in T2D [130–132] results in impaired learning and immediate memory.”
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“And metabolic disturbances, particularly type 2 diabetes (T2D) increase the risk of cognitive impairment and AD (Stewart and Liolitsa, 1999; Pugazhenthi et al., 2017; Boccardi et al., 2019).”
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“It is established that the well-known cerebrovascular complications of non-insulin-dependent diabetes mellitus (Ott et al., 1999; Stewart & Liolitsa, 1999; Wannamethee et al., 1999) interact with AD pathology in causing cognitive decline (Schneider et al., 2007).”
BackgroundDNA methylation patterns of LINE-1 and Alu for pre-symptomatic dementia in type 2 diabetes
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“Other risk factor combinations have also been used: stroke + diabetes (Stewart and Liolitsa, 1999); stroke + stress (Madrigal et al., 2003); stress + seizures (Srinivasan et al., 2006); stress + aging (Lupien et al., 1998; Sapolsky, 1999).”
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“Althoughmost of the AD cases are sporadic, occur later in life (aged >65 years) and have no known cause, the disease is associated with several vascular risk factors, especially type 2 diabetes (T2D) mellitus (Arvanitakis et al., 2004; Stewart and Liolitsa, 1999), which more than doubles the risk of developing AD (Sch…”
BackgroundThe brain of the elderly diabetic patient
Bauduceau, B., Bourdel‐Marchasson, I., Brocket, P., & Taillia, H. (2005) · Diabetes & Metabolism · doi:10.1016/s1262-3636(05)73657-0 · Cited by 22
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“However, the association between the AKT1 rs2498786 polymorphism and AD was independent of T2D status, which may be explained by the increasing evidence demonstrating that AD has some pathological features in common with T2D, and the two disorders may share a similar etiology [26].”
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“The brain is one of the organs in which diabetes causes electrophysiological and degenerative changes and a decrease in cognitive functions, which collectively are termed diabetic encephalopathy (Biessels et al., 1994; Manschot et al., 2007; Mastrocola et al., 2005; Reske-Nielsen et al., 1965; Stewart and Liolitsa, 19…”
BackgroundSasaki‐Hamada, S., Hojo, Y., Koyama, H., Otsuka, H., & Oka, J. (2015) · European Journal of Neuroscience · doi:10.1111/ejn.12891 · Cited by 23
“Several reviews have shown that type 2 DM is associated with cognitive impairments (Strachan et al., 1997; Stewart & Liolitsa, 1999; Awad et al., 2002; Biessels et al., 2002), and longitudinal research revealed that type 2 DM could result in accelerated cognitive decline (Allen et al., 2004;…”
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Nursing Care of Older People with Diabetes
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“The morbidity of cognitive impairment is particularly increased in T2DM patients older than 65 years [3].”
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“Epidemiological studies suggest that cognitive impairment and decline are linked to individual-level characteristics including age [1], race/ethnicity [2, 3], education/socioeconomic status [4–7], vascular conditions [8, 9], and social integration/support [10].”
BackgroundAuditory P300 event-related potentials in patients with type 2 diabetes mellitus
Andreadou, E., Mitrakou, A., Constantinides, V. C., & Triantafyllou, N. I. (2012) · journal of Diabetes Research and Clinical Metabolism · doi:10.7243/2050-0866-1-1 · Cited by 18
Hassing, L. B., Johansson, B. E. A., Pedersen, N. L., Nilsson, S. E., Berg, S., & McClearn, G. E. (2003) · Aging Neuropsychology and Cognition · doi:10.1076/anec.10.2.99.14458 · Cited by 18
“In a recent review on the diabetes-cognition research, Stewart and Liolitsa (1999) pointed out that many of the studies up to date suffer from various methodological problems.”
BackgroundEffects of Hypertension and Diabetes on Sentence Comprehension in Aging
Cahana-Amitay, D., Albert, M. L., Ojo, E. A., Sayers, J. T., Goral, M., Obler, L. K., & Spiro, A. (2012) · The Journals of Gerontology Series B · doi:10.1093/geronb/gbs085 · Cited by 18
ε-Glycation, APP and Aβ in ageing and Alzheimer disease: A hypothesis
Schmitt, H. P. (2006) · Medical Hypotheses · doi:10.1016/j.mehy.2005.11.016 · Cited by 19
“The formation and tissue deposition of AGEs has been shown to be particularly increased in type 2 diabetes mellitus [78], in which age-related decline of cognitive functions appears to be accelerated [93] and the risk of dementia seems to be increased [64,90,91,114], presumably (but not unequivocally) including the de…”
BackgroundHalling, A., & Berglund, J. S. (2006) · Scandinavian Journal of Primary Health Care · doi:10.1080/02813430500428919 · Cited by 17
“Both HF and DM have been shown to be independently associated with poorer cognitive function [20,21].”
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elaaty, T. A., Ismail, A. A., Sheshtawy, H. A., Sultan, E. A., & Ebrahim, M. G. (2019) · Diabetes & Metabolic Syndrome Clinical Research & Reviews · doi:10.1016/j.dsx.2019.03.012 · Cited by 17
Heng, L., Yang, R., & Jia, D. (2011) · Behavioural Brain Research · doi:10.1016/j.bbr.2011.05.043 · Cited by 17
iabetic Encephalopathy Affecting Mitochondria and Axonal Transport Proteins
Eslami, M. (2020) · Basic and Clinical Neuroscience Journal · doi:10.32598/bcn.11.6.1657.1 · Cited by 16
“Following prolonged DM, the impaired hippocampal plasticity may damage learning and memory processing (Flood, Mooradian, & Morley, 1990; Stewart & Liolitsa, 1999; Stranahan et al., 2008).”
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Cerebral antioxidant enzyme increase associated with learning deficit in type 2 diabetes rats
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Ishii, D., & Šerbed�ija, P. (2012) · Indian Journal of Endocrinology and Metabolism · doi:10.4103/2230-8210.105578 · Cited by 16
Mruthinti, S., Hill, W., Swamy-Mruthinti, S., & Buccafusco, J. J. (2003) · Journal of Molecular Neuroscience · doi:10.1385/jmn:20:3:223 · Cited by 17
“Whereas the production and cytotoxicity of glycated proteins are more commonly associated with diabetes (and diabetes may constitute a risk factor for AD [Ott et al., 1996; Stewart and Liolitsa 1999 ]), glycation of neural proteins over time is associated with inflammation and the production of free radical species (S…”
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“Large amounts of studies suggest that diabetes mellitus are accompanied with impaired cognitive functions [7-11].”
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“Numerous studies have demonstrated that T2DM can increase the risk of cognitive impairment and may even progress to dementia, such as vascular dementia and Alzheimer’s disease (AD) (Stewart and Liolitsa, 1999; Strachan et al., 2011; Moran et al., 2019; Alkethiri et al., 2021).”
BackgroundBenfotiamine prevents increased β-amyloid production in HEK cells induced by high glucose
Sun, X., Zhao, L., Zhao, N., Pan, X.-L., Fei, G.-Q., Jin, L., & Zhong, C. (2012) · Neuroscience Bulletin · doi:10.1007/s12264-012-1264-0 · Cited by 15
“Mild to moderate impairments of cognitive functions have been reported in patients with Type I([16]) and Type II DM([17,18]).”
BackgroundDiabetes and cognitive functioning: The role of age and comorbidity
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“In the 1990s, the link between DM and some dementias, such as AD and DaV, was already discussed [86].”
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“…findings from earlier studies that depression (Yaffe et al 1999; Wilson et al 2004), amounts of exercise (Laurin et al 2001), metabolic syndrome (Stewart and Liolitsa 1999; Yaffe et al 2004), and regular consumption of alcohol (Pinder and Sandler 2004) modulate the risk for cognitive impairment…”
The Prevalence of Cognitive Impairment among Older Adults in Jamaica
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“Cognitive impairment and dementia have been associated with rural dwellers (16), increased rates of hospitalization (17, 18), increased risk for falls (19, 20), increased prevalence of fear of falling (21, 22), diabetes mellitus (23, 24), depression (17, 25), and dependence in activities of daily living [ADL] (26).”
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“Epidemiological studies have shown that persons with Type 2 diabetes have a twofold increased risk of developing either Alzheimer’s Disease or vascular dementia, with strong interaction of other factors such as hypertension, dyslipidemia, and apolipoprotein E phenotype [11].”
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“Several large population-based studies have demonstrated that diabetes increases the risk of cognitive impairment [27-29], and the disease duration is associated with cognitive decline [17].”
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“studies have reported reduced cognitive functions in diabetic patients, especially among the elderly; however, the exact mechanism for this condition is not clear.(2,3) The rise in the number of diabetic elderly patients mandates close evaluation of dementia and cognitive functional disorders in this particular popula…”
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Synergistic Effect of Serum Homocysteine and Diabetes Mellitus on Brain Alterations
Byeon, G., Byun, M. S., Yi, D., Lee, J. H., Jeon, S. Y., Ko, K., Jung, G., Lee, J., Kim, Y. K., Lee, Y., et al. (2021) · Journal of Alzheimer s Disease · doi:10.3233/jad-210036 · Cited by 11
“Both elevated blood homocysteine [1–3] and diabetes mellitus (DM) [4–6] are related to cognitive impairments or clinically defined dementias including Alzheimer’s disease (AD) dementia.”
Kim, J. W., Chae, J., Nam, S. M., Kim, Y. N., Yoo, D. Y., Choi, J. H., Jung, H. Y., Song, W. J., Hwang, I. K., Seong, J. K., et al. (2015) · Journal of Veterinary Science · doi:10.4142/jvs.2015.16.1.11 · Cited by 10
Investigational treatment for vascular cognitive impairment
Birks, J., & Flicker, L. A. (2007) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.16.5.647 · Cited by 10
“Memory loss is not necessarily as prominent in VCI as in Alzheimer’s disease [16].”
BackgroundEze, C. O. (2015) · Journal of Metabolic Syndrome · doi:10.4172/2167-0943.1000171 · Cited by 10
“Type 2 diabetes mellitus (DM2) is associated with cognitive impairment [3].”
BackgroundBrain Insulin Signaling is Associated with Late-Life Cognitive Decline
Tong, H., Capuano, A. W., Carmichael, O. T., Gwizdala, K. L., Bennett, D. A., Ahima, R. S., Arnold, S. E., & Arvanitakis, Z. (2023) · Aging and Disease · doi:10.14336/ad.2023.1117 · Cited by 11
“Accumulating evidence suggests that T2DM and cognitive impairment are linked [2-4].”
BackgroundCognitive and psychosocial aspects of caring for elderly patients with diabetes
Iwata, I., & Munshi, M. N. (2009) · Current Diabetes Reports · doi:10.1007/s11892-009-0024-7 · Cited by 9
“Stewart and Liolitsa [ 6 ] summarized more than 20 case-control studies and found that the defi cit in the attention/concentration domain and verbal fl uency among patients with diabetes appeared to be consistent.”
BackgroundSachar, A. (2013) · London Journal of Primary Care · doi:10.1080/17571472.2013.11493377 · Cited by 9
The Association Between Diabetes and Cognitive Function in Later Life
Momtaz, Y. A., Hamid, T. A., Bagat, M. F., & Hazrati, M. (2019) · Current Aging Science · doi:10.2174/1874609812666190614104328 · Cited by 9
“growing body of scientific investigations indicating that diabetes is associated with an increased risk of developing cognitive impairment and dementia [31-33], the findings from the current study revealed that diabetic respondents had a higher score of cognitive function.”
ResultLi, Y., Hui, C. L. M., Lee, E. H. M., Chang, W. C., Chan, S. K. W., Leung, C., & Chen, E. Y. H. (2013) · Early Intervention in Psychiatry · doi:10.1111/eip.12109 · Cited by 9
Basal ganglia calcification in BB/E rats with diabetes
Lammie, G. A., Kelly, P. A. T., BAIRD, J. D., Smith, W., Chatterjee, S., Frier, B. M., & Strachan, M. W. J. (2005) · Journal of Clinical Neuroscience · doi:10.1016/j.jocn.2004.03.026 · Cited by 9
Diabetes and elevated glycosylated haemoglobin: Episodic memory and utilisation of cognitive support
Nilsson, E. D., & Wåhlin, Å. (2008) · The European Journal of Cognitive Psychology · doi:10.1080/09541440802333133 · Cited by 9
“Diabetes is also related to an increased risk of developing Alzheimer’s disease (AD), and other dementias (see, e.g., Ott et al., 1996; Stewart & Liolitsa, 1999; Xu, Qiu, Wahlin, Winblad, & Fratiglioni, 2004).”
BackgroundPsychiatric Disorders and Psychotropic Medication Use in Elderly Persons with Diabetes
Feil, D. G., Weinreb, J. E., & Sultzer, D. L. (2006) · Cited by 9
Francoeur, R. B. (2016) · Diabetes Metabolic Syndrome and Obesity · doi:10.2147/dmso.s118432 · Cited by 10
“Obesity and diabetes may share similar pathways in contributing to late-life dementia since both conditions are associated with atrial fibrillation, in part through their role in precipitating obstructive sleep apnea.(28,30) Thus, disease-specific effects of obesity and diabetes may aggravate existing vascular conditi…”
Design of human centered augmented reality for managing chronic health conditions
McLaughlin, A. C., Matalenas, L. A., & Coleman, M. G. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-811272-4.00011-7 · Cited by 9
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Hernández, C. F., Villamán, C., Leu, C., Lal, D., Mata, I. F., Klein, A. D., & Pérez‐Palma, E. (2025) · Scientific Reports · doi:10.1038/s41598-025-95755-8 · Cited by 9
“Even after controlling for diabetic vascular disease and inadequate cerebral circulation, increased cortical and subcortical atrophy have been observed in T2D patients 33,34 .”
A positive effect of intranasal insulin on spatial memory in rats with neonatal diabetes mellitus
Chistyakova, O. V., Бондарева, В. М., Шипилов, В. Н., Sukhov, I. B., & Shpakov, A. O. (2011) · Endocrinology Studies · doi:10.4081/es.2011.e16 · Cited by 8
Diabetes and the Nervous System
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Curtis, S., Beirne, J., & Jude, E. B. (2003) · Practical Diabetes · doi:10.1002/pdi.506 · Cited by 8
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Yu, W., Yin, H., Sun, Y., Shi, S., Li, J., & Wang, X. (2022) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.13847 · Cited by 7
How Effective are Gliflozins as DPP-4 Inhibitors? A Computational Study
Saini, K., Khan, Y., & Sharma, S. (2023) · Theoretical Foundations of Chemical Engineering · doi:10.1134/s0040579523030168 · Cited by 7
Stott, D. J. (2006) · ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) · Cited by 7
The Influences of Dietary Sugar and Related Metabolic Disorders on Cognitive Aging and Dementia
Seetharaman, S. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-801816-3.00024-8 · Cited by 7
Youth-Onset Type 2 Diabetes and the Developing Brain
Redel, J. M., Dolan, L. M., DiFrancesco, M. W., Vannest, J. J., & SHAH, A. S. (2019) · Current Diabetes Reports · doi:10.1007/s11892-019-1120-y · Cited by 7
Shishkova, V. N. (2015) · Terapevticheskii arkhiv · doi:10.17116/terarkh2015871109-114 · Cited by 7
Hirschstein, Z., Novakovic, Z. M., & Grasso, P. (2019) · International Journal of Peptide Research and Therapeutics · doi:10.1007/s10989-019-09995-0 · Cited by 7
Fan, X., O’Donnell, A., Singh, S. P., Pungan, R., & Perlmuter, L. C. (2008) · Experimental Aging Research · doi:10.1080/03610730701876953 · Cited by 7
“In addition, diabetes is associated with an elevated risk of vascular or probable Alzheimer's dementia (Stewart & Liolitsa, 1999 ).”
Background
Metadata
- 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
- 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
- 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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