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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Background
Diabetes Mellitus Is a Risk Factor for Vascular Dementia, but Not for Alzheimer’s Disease: A Population-Based Study of the Oldest Old
Hassing, L. B., Johansson, B. E. A., Nilsson, S. E., Berg, S., Pedersen, N. L., Gatz, M., & McClearn, G. E. (2002) · International Psychogeriatrics · doi:10.1017/s104161020200844x · Cited by 175
Role of apolipoprotein E in neurodegenerative diseases
Giau, V. V., Bagyinszky, E., An, S. S. A., & Kim, S. (2015) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s84266 · Cited by 177
“Recently, studies have showed that older patients with T2DM have a higher risk of cognitive dysfunction or dementia.(98) Moreover, T2DM was related not only to VD, but also to the clinical diagnosis of AD-type dementia.”
Background
Cognitive impairment and MRI correlates in the elderly patients with type 2 diabetes mellitus
van Harten, B., Oosterman, J. M., Muslimović, D., van Loon, B. J. P., Scheltens, P., & Weinstein, H. C. (2007) · Age and Ageing · doi:10.1093/ageing/afl180 · Cited by 171
“Results of the subjective memory questionnaire, global cognitive functioning tests, different cognitive domains and individual neuropsychological tests DM Control subjects P-value d . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .…”
BackgroundMethodInfluential
Change in Cognitive Performance From Midlife Into Old Age: Findings from the Midlife in the United States (MIDUS) Study
Hughes, M. L., Agrigoroaei, S., Jeon, M., Bruzzese, M., & Lachman, M. E. (2018) · Journal of the International Neuropsychological Society · doi:10.1017/s1355617718000425 · Cited by 177
“…& D’Agostino, 2000; Karlamangla et al., 2005), sensory/motor functioning (Lindenberger & Baltes, 1994; Wingfield, Tun, & McCoy, 2005), diabetes (Stewart & Liolitsa, 1999; Wu et al., 2008; Yeung, Fischer, & Dixon, 2009), stress and allostatic load (Seeman, McEwen, Singer, Albert, & Rowe,…”
Cognition in the Early Stage of Type 2 Diabetes
Ruis, C., Biessels, G. J., Gorter, K. J., van den Donk, M., Kappelle, L. J., & Rutten, G. E. H. M. (2009) · Diabetes Care · doi:10.2337/dc08-2143 · Cited by 171
“Previous studies have shown decrements in memory function, executive function, and information-processing speed (4,5).”
Result
Effect of Intranasal Insulin on Cognitive Function: A Systematic Review
Shemesh, E., Rudich, A., Harman-Boehm, I., & Cukierman-Yaffe, T. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-1802 · Cited by 162
Insulin resistance and pathological brain ageing
Cholerton, B., Baker, L. D., & Craft, S. (2011) · Diabetic Medicine · doi:10.1111/j.1464-5491.2011.03464.x · Cited by 164
Maintained exercise‐enhanced brain executive function related to cerebral lactate metabolism in men
Hashimoto, T., Tsukamoto, H., Takenaka, S., Olesen, N. D., Petersen, L. G., Sørensen, H., Nielsen, H. B., Secher, N. H., & Ogoh, S. (2018) · The FASEB Journal · doi:10.1096/fj.201700381rr · Cited by 156
A high fructose diet impairs spatial memory in male rats
Ross, A. P., Bartness, T. J., Mielke, J. G., & Parent, M. B. (2009) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2009.05.007 · Cited by 162
“For instance, extensive evidence suggests that peripheral insulin resistance and type 2 diabetes are associated with deficits in hippocampal-dependent declarative memory (Convit, 2005; Messier, 2005; Stewart and Liolitsa, 1999; Strachan, Deary, Ewing, and Frier, 1997; Zhao, Chen, Xu, Moore, Meiri, Quon, and Alkon, 199…”
Background
Guidelines for Improving the Care of the Older Person with Diabetes Mellitus
Ickowicz, E. (2003) · Cited by 152
Impairments in glucose tolerance can have a negative impact on cognitive function: A systematic research review
Lamport, D. J., Lawton, C. L., Mansfield, M. W., & Dye, L. (2008) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2008.10.008 · Cited by 156
“Several reviews have shown that type 2 diabetes is associated with cognitive impairments (Awad et al., 2004; Biessels et al., 2002; Stewart and Liolitsa, 1999; Strachan et al., 1997), and longitudinal research has shown that type 2 diabetes can result in accelerated cognitive decline (Allen et al.,…”
Cerebral dysfunction in type 1 diabetes: effects of insulin, vascular risk factors and blood-glucose levels
Brands, A. M. A., Kessels, R. P. C., de Haan, E. H. F., Kappelle, L. J., & Biessels, G. J. (2004) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2004.02.053 · Cited by 154
A four-day Western-style dietary intervention causes reductions in hippocampal-dependent learning and memory and interoceptive sensitivity
Attuquayefio, T., Stevenson, R. J., Oaten, M., & Francis, H. (2017) · PLoS ONE · doi:10.1371/journal.pone.0172645 · Cited by 155
Cognitive impairment, physical disability and depressive symptoms in older diabetic patients: the Fremantle Cognition in Diabetes Study
Bruce, D. G., Casey, G. P., Grange, V., Clarnette, R. C., Almeida, O. P., Foster, J. K., Ives, F. J., & Davis, T. M. E. (2003) · Diabetes Research and Clinical Practice · doi:10.1016/s0168-8227(03)00084-6 · Cited by 145
Peripheral Hyperinsulinemia Promotes Tau Phosphorylation In Vivo
Freude, S., Plum, L., Schnitker, J., Leeser, U., Udelhoven, M., Krone, W., Brüning, J. C., & Schubert, M. (2005) · Diabetes · doi:10.2337/diabetes.54.12.3343 · Cited by 147
Risk of Hypoglycemia in Older Veterans with Dementia and Cognitive Impairment: Implications for Practice and Policy
Feil, D. G., Rajan, M., Soroka, O., Tseng, C., Miller, D. R., & POGACH, L. M. (2011) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2011.03726.x · Cited by 145
Self‐Reported Goals of Older Patients with Type 2 Diabetes Mellitus
Huang, E. S., Gorawara‐Bhat, R., & Chin, M. H. (2005) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2005.53119.x · Cited by 139
Antidiabetic drugs restore abnormal transport of amyloid-β across the blood–brain barrier and memory impairment in db/db mice
Chen, F., Dong, R. R., Zhong, K. L., Ghosh, A., Tang, S. S., Long, Y., Hu, M. Y., Miao, M. X., Liao, J. M., Sun, H. B., et al. (2015) · Neuropharmacology · doi:10.1016/j.neuropharm.2015.07.023 · Cited by 137
Cognitive function and information processing in Type 2 diabetes
Cosway, R., Strachan, M. W. J., Dougall, A., Frier, B. M., & Deary, I. J. (2001) · Diabetic Medicine · doi:10.1046/j.1464-5491.2001.00577.x · Cited by 137
Brain Lesions on MRI in Elderly Patients with Type 2 Diabetes Mellitus
van Harten, B., Oosterman, J. M., van Loon, B. J. P., Scheltens, P., & Weinstein, H. C. (2006) · European Neurology · doi:10.1159/000098054 · Cited by 135
“Diabetes mellitus (DM) has been associated with cognitive impairment and dementia, particularly in the elderly [”
Background
Overweight and cognition
Nilsson, L., & Nilsson, E. D. (2009) · Scandinavian Journal of Psychology · doi:10.1111/j.1467-9450.2009.00777.x · Cited by 133
Cognitive dysfunction and hippocampal changes in experimental type 1 diabetes
Alvarez, E. O., Beauquis, J., Revsin, Y., Banzán, A. M., Roig, P., Nicola, A. F. D., & Saravia, F. (2008) · Behavioural Brain Research · doi:10.1016/j.bbr.2008.11.001 · Cited by 131
Statins for the prevention of dementia
McGuinness, B., Craig, D., Bullock, R., & Passmore, P. (2016) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd003160.pub3 · Cited by 490
Vascular risk factors and Alzheimer’s disease
Cechetto, D. F., Hachinski, V., & Whitehead, S. N. (2008) · Expert Review of Neurotherapeutics · doi:10.1586/14737175.8.5.743 · Cited by 133
Low BDNF is associated with cognitive deficits in patients with type 2 diabetes
Zhen, Y. F., Zhang, J., Liu, X. Y., Fang, H., Tian, L. B., Zhou, D. H., Kosten, T. R., & Zhang, X. Y. (2013) · Psychopharmacology · doi:10.1007/s00213-012-2942-3 · Cited by 126
“…performance in T2DM patients in our present study is concordant with most of the studies evaluating cognitive function in patients with T2DM (Stewart et al. 1999; Gold et al. 2007; Nooyens et al. 2010; Szémán et al. 2012), and with the higher risk that T2DM patients have for cognitive…”
Result
Hypercholesterolaemia and vascular dementia
Appleton, J. P., Scutt, P., Sprigg, N., & Bath, P. M. (2017) · Clinical Science · doi:10.1042/cs20160382 · Cited by 129
The impact of diabetes mellitus on cognitive decline in the oldest of the old: a prospective population-based study
van den Berg, E., de Craen, A. J. M., Biessels, G. J., Gussekloo, J., & Westendorp, R. G. J. (2006) · Diabetologia · doi:10.1007/s00125-006-0333-1 · Cited by 126
“While hypertension has been suggested to be an important determinant of impaired cognition in diabetes [ 4 ], in the present study no clear relationship was found between hypertension and cognitive function within the group of diabetes patients, in line with other recent studies [27, 29].”
Result
Reduced hippocampal neurogenesis and number of hilar neurones in streptozotocin‐induced diabetic mice: reversion by antidepressant treatment
Beauquis, J., Roig, P., Homo‐Delarche, F., Nicola, A. F. D., & Saravia, F. (2006) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2006.04691.x · Cited by 132
“…performance in neuropsychological tests, impairments in learning and memory, high risk of dementia, Alzheimer’s disease and elevated incidence of depression (Flood et al., 1990; McCall, 1992; Biessels et al., 1994; Mankovsky, 1997; Helgason, 1998; Ott et al., 1999; Stewart & Liolitsa, 1999).”
Background
Glycogen synthase kinase-3 is increased in white cells early in Alzheimer's disease
Hye, A., Kerr, F., Archer, N. J., Foy, C., Poppe, M., Brown, R. G., Hamilton, G., Powell, J. F., Anderton, B. H., & Lovestone, S. (2004) · Neuroscience Letters · doi:10.1016/j.neulet.2004.10.031 · Cited by 130
Insulin-like growth factor I (IGF-I) and cognitive decline in older persons
Dik, M. G., Pluijm, S. M. F., Jonker, C., Deeg, D. J. H., Lomecky, M. Z., & Lips, P. T. A. M. (2003) · Neurobiology of Aging · doi:10.1016/s0197-4580(02)00136-7 · Cited by 124
Glycaemic Control for People with Type 2 Diabetes Mellitus in Bangladesh - An urgent need for optimization of management plan
Afroz, A., Ali, L., Karim, M. N., Alramadan, M. J., Alam, K., Magliano, D. J., & Billah, B. (2019) · Scientific Reports · doi:10.1038/s41598-019-46766-9 · Cited by 123
Exploring effects of type 2 diabetes on cognitive functioning in older adults.
Yeung, S. E., Fischer, A. L., & Dixon, R. A. (2009) · Neuropsychology · doi:10.1037/a0013849 · Cited by 124
“Third, selected measures of executive functioning have produced diabetes-related performance deficits in some (but not all) studies (Awad et al., 2004; Messier, 2005; Ryan & Geckle, 2000; Stewart & Liolitsa, 1999).”
Cross-Sectional Relationships of Physical Activity and Sedentary Behavior With Cognitive Function in Older Adults With Probable Mild Cognitive Impairment
Falck, R. S., Landry, G. J., Best, J. R., Davis, J. C., Chiu, B. K., & Liu-Ambrose, T. Y. L. (2017) · Physical Therapy · doi:10.1093/ptj/pzx074 · Cited by 127

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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