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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Items 201–300 of 563

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Fischer, A. L., de Frias, C. M., Yeung, S. E., & Dixon, R. A. (2009) · Journal of Clinical and Experimental Neuropsychology · doi:10.1080/13803390802537636 · Cited by 51
“Findings on the broad and multidimensional construct of executive function are similarly mixed in the diabetes literature and are likely related to the fact that single tests may represent different aspects of the domain for both healthy and special populations of older adults ( Awad et al, 2004 ; de Frias, Dixon, & S…”
Neuropsychological functioning in older people with Type 2 diabetes: the effect of controlling for confounding factors
Asimakopoulou, K. G., Hampson, S. E., & Morrish, N. J. (2002) · Diabetic Medicine · doi:10.1046/j.1464-5491.2002.00680.x · Cited by 50
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Meng, L., Li, X., Shen, L., & Ji, H. (2020) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2020.02.002 · Cited by 49
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de Moraes, S. A., Szklo, M., Knopman, D. S., & Sato, R. (2002) · Preventive Medicine · doi:10.1006/pmed.2002.1077 · Cited by 49
Vascular risk factors and cognitive decline among elderly male twins
Xiong, G. L., Plassman, B. L., Helms, M. J., & Steffens, D. C. (2006) · Neurology · doi:10.1212/01.wnl.0000242730.44003.1d · Cited by 49
Cranial Volume, Mild Cognitive Deficits, and Functional Limitations Associated with Diabetes in a Community Sample
Christman, A. L., Vannorsdall, T. D., Pearlson, G. D., Hill‐Briggs, F., & Schretlen, D. J. (2009) · Archives of Clinical Neuropsychology · doi:10.1093/arclin/acp091 · Cited by 48
“The two existing major published reviews of cognition studies in diabetes (Stewart & Liolitsa, 1999; Strachan, Dreary, Ewing, & Frier, 1997a) * Corresponding author at: Welch Center for Prevention, Epidemiology, and Clinical Research, 2024 E. Monument Street, Suite 2-600, Baltimore, MD 21287, USA.”
Background
Spatial working memory impairment in primary onset middle-age type 2 diabetes mellitus: An ethology and BOLD-fMRI study
Huang, R., Jia, B., Xie, L., Ma, S., Yin, J., Sun, Z., Le, H., Xu, W., Huang, J., & Luo, D.-X. (2015) · Journal of Magnetic Resonance Imaging · doi:10.1002/jmri.24967 · Cited by 49
“Some neuropsychological studies have reported that DM patients have mild cognitive impairment (MCI), particularly for tasks involving verbal memory or complex information processing.(5,6) Ruis et al 7 found that MCI was already present in the early stages of T2DM patients, and Dey et al 8 reported cognitive impairment…”
Background
Cognitive functioning and structural brain abnormalities in people with Type 2 diabetes mellitus
Mankovsky, B., Zherdova, N., van den Berg, E., Biessels, G. J., & de Bresser, J. (2018) · Diabetic Medicine · doi:10.1111/dme.13800 · Cited by 48
Metabolic profile of the hippocampus of Zucker Diabetic Fatty rats assessed by in vivo1H magnetic resonance spectroscopy
van der Graaf, M., Janssen, S. W. J., van Asten, J. J. A., Hermus, A. R., Sweep, F. C. G. J., Pikkemaat, J. A., Martens, G. J. M., & Heerschap, A. (2004) · NMR in Biomedicine · doi:10.1002/nbm.896 · Cited by 48
“especially in older type 2 diabetic patients, cognitive deficits can be observed.(5) In diabetic rats, central nervous system damage is characterized by impairment of learning and memory, changes in synaptic plasticity and neurophysiologic alterations.”
Background
Risk factors associated with cognitive decline in the elderly with type 2 diabetes: Baseline data analysis of the Japanese elderly diabetes intervention trial
Umegaki, H., Iimuro, S., Shinozaki, T., Araki, A., Sakurai, T., Iijima, K., Ohashi, Y., Ito, H., & the Japanese Elderly Diabetes Intervention Trial Study Group (2012) · Geriatrics and gerontology international/Geriatrics & gerontology international · doi:10.1111/j.1447-0594.2011.00817.x · Cited by 50
Chronic Cyanidin‐3‐glucoside Administration Improves Short‐term Spatial Recognition Memory but not Passive Avoidance Learning and Memory in Streptozotocin‐diabetic Rats
Nasri, S., Roghani, M., Baluchnejadmojarad, T., Balvardi, M., & Rabani, T. (2012) · Phytotherapy Research · doi:10.1002/ptr.3702 · Cited by 47
“…pathogenesis of cognitive and memory impairments in diabetes is not completely understood, several factors such as metabolic impairments, vascular complications and enhanced release of free radicals have been implicated (Stewart and Liolitsa, 1999; Biessels et al., 2007; Kucukatay et al., 2007).”
Background
Lipidomic Profiles in Diabetes and Dementia
Huynh, K., Martins, R. N., & Meikle, P. J. (2017) · Journal of Alzheimer s Disease · doi:10.3233/jad-161215 · Cited by 47
“It is now established that T2D is associated with poorer cognitive outcomes, especially in the elderly [12], and in the past decade, mounting evidence suggests T2D as a strong risk factor for dementia and AD [13].”
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Wiberg, B., Lind, L., Kilander, L., Zethelius, B., Sundelöf, J. E., & Sundström, J. (2010) · Neurology · doi:10.1212/wnl.0b013e3181ccc516 · Cited by 46
Potential hippocampal region atrophy in diabetes mellitus type 2: a voxel-based morphometry VSRAD study
Kamiyama, K., Wada, A., SUGIHARA, M., Kurioka, S., Hayashi, K., Hayashi, T., Yoshisako, T., Yamamoto, N., Tsuchie, Y., Yamaguchi, S., et al. (2010) · Japanese Journal of Radiology · doi:10.1007/s11604-009-0416-2 · Cited by 46
Cerebrospinal fluid levels of insulin in patients with Alzheimer's disease
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Longitudinal evaluation of memory performance and peripheral neuropathy in the Ins2C96Y Akita mice
Choeiri, C., Hewitt, K. E., Durkin, J. P., Simard, C. J., Renaud, J., & Messier, C. (2004) · Behavioural Brain Research · doi:10.1016/j.bbr.2004.06.005 · Cited by 48
Short-Term Effects of Improved Glycemic Control on Cognitive Function in Patients with Type 2 Diabetes
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Age, vascular risk, and cognitive decline in an older, British, African-Caribbean population.
Stewart, R., Prince, M., & Mann, A. (2003) · Journal of the American Geriatrics Society · doi:10.1046/j.1532-5415.2003.51504.x · Cited by 45
“Diabetes mellitus may modify the association between age and cognitive decline through several mechanisms, including levels of cerebrovascular disease, cerebral effects of hyper- or hypoglycemia, and potentially common pathways underlying insulin resistance and neurodegeneration.(37) Causal pathways are of relevance f…”
Background
Methylglyoxal can mediate behavioral and neurochemical alterations in rat brain
Hansen, F., Pandolfo, P., Galland, F., Torres, F. V., Dutra, M. F., Batassini, C., Guerra, M. C., Leite, M. C., & Gonçalves, C. (2016) · Physiology & Behavior · doi:10.1016/j.physbeh.2016.05.046 · Cited by 45
Risk factors associated with cognitive decline in the elderly with type 2 diabetes: Pooled logistic analysis of a 6‐year observation in the Japanese elderly diabetes intervention trial
Umegaki, H., Iimuro, S., Shinozaki, T., Araki, A., Sakurai, T., Iijima, K., Ohashi, Y., Ito, H., & the Japanese Elderly Diabetes Intervention Trial Study Group (2012) · Geriatrics and gerontology international/Geriatrics & gerontology international · doi:10.1111/j.1447-0594.2011.00818.x · Cited by 45
Genetic variability in the insulin signalling pathway may contribute to the risk of late onset Alzheimer's disease
Liolitsa, D. (2002) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.73.3.261 · Cited by 45
Self-citation
The Association Between Light Physical Activity and Cognition Among Adults: A Scoping Review
Erlenbach, E. D., McAuley, E., & Gothe, N. P. (2021) · The Journals of Gerontology Series A · doi:10.1093/gerona/glab013 · Cited by 51
Excessive daytime sleepiness in migraine patients
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The effect of gamma-linolenic acid–alpha-lipoic acid on functional deficits in the peripheral and central nervous system of streptozotocin-diabetic rats
Biessels, G. J., Smale, S., Duis, S., Kamal, A., & Gispen, W. H. (2001) · Journal of the Neurological Sciences · doi:10.1016/s0022-510x(00)00456-1 · Cited by 43
Cardiovascular Risk Factors Cause Cortical Thinning in Cognitively Impaired Patients
Seo, S. W., Lee, J., Im, K., Park, J.-S., Kim, S.-H., Kim, S. T., Ahn, J., Kim, M.-J., Kim, G. H., Kim, J., et al. (2011) · Alzheimer Disease & Associated Disorders · doi:10.1097/wad.0b013e31822e0831 · Cited by 42
“Our findings may be in line with previous neuropsychological results showing that DM correlated with cognitive impairments in attention, executive functioning, and/or information processing.(29,30) The lack of association between hyperlipidemia and cortical thinning is notable, because hyperlipidemia is an important r…”
Result
The etiology of age-related dementia is more complicated than we think
McDonald, R. J., Craig, L. A., & Hong, N. S. (2010) · Behavioural Brain Research · doi:10.1016/j.bbr.2010.05.005 · Cited by 42
Ethnic Differences in Geriatric Conditions and Diabetes Complications Among Older, Insured Adults With Diabetes
Karter, A. J., Laiteerapong, N., Chin, M. H., Moffet, H. H., Parker, M. M., Sudore, R. L., Adams, A. S., Schillinger, D., Adler, N., Whitmer, R. A., et al. (2015) · Journal of Aging and Health · doi:10.1177/0898264315569455 · Cited by 49
“However, the basic epidemiology of geriatric conditions, particularly with respect to ethnic differences, has not been well studied in older patients with diabetes (Anderson et al., 2001; Bertoni, Krop, Anderson, & Brancati, 2002; J. S. Brown, et al., 1996; Stewart & Liolitsa, 1999).”
Background
Kinase–Kinase Interaction and Modulation of Tau Phosphorylation
Hashiguchi, M., & Hashiguchi, T. (2012) · International review of cytology · doi:10.1016/b978-0-12-405210-9.00004-7 · Cited by 44
Central nervous system involvement in diabetes mellitus
Selvarajah, D., & Tesfaye, S. H. (2006) · Current Diabetes Reports · doi:10.1007/s11892-006-0075-y · Cited by 42
“Epidemiologic studies have reported that diabetes is an independent risk factor for cognitive impairment [3, 4 ].”
BackgroundInfluential
Mild impairments in cognition in patients with type 2 diabetes mellitus: the use of the concepts MCI and CIND
van den Berg, E. (2005) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.2005.062737 · Cited by 42
Diabetes and dementia
Lovestone, S. (1999) · Neurology · doi:10.1212/wnl.53.9.1907 · Cited by 42
Editorial: Diabetes Mellitus: A Major Disease Of Older Persons
Morley, J. E. (2000) · The Journals of Gerontology Series A · doi:10.1093/gerona/55.5.m255 · Cited by 42
Protein and lipid oxidative damage in streptozotocin-induced diabetic rats submitted to forced swimming test: the insulin and clonazepam effect
Wayhs, C. A. Y., Manfredini, V., Sitta, Â., Deon, M., Ribas, G. S., Vanzin, C. S., Biancini, G. B., Ferri, M. K., Nin, M. S., Barros, H. M. T., et al. (2010) · Metabolic Brain Disease · doi:10.1007/s11011-010-9211-0 · Cited by 41
“Since the early 20th century the cognitive dysfunction of diabetic subjects has been recognized (Miles and Root 1922) and several studies of diabetic subjects have described neuropsychological and neurobehavioral changes (Strachan et al. 1997; Stewart and Liolitsa 1999), suggesting that diabetic encephalopathy could b…”
Background
The Effect of Green Tea Extract on Oxidative Stress and Spatial Learning in Streptozotocin-diabetic Rats.
Sharifzadeh, M. S., Ranjbar, A., Hosseini, A., & Khanavi, M. (2017) · PubMed Central · Cited by 41
Insulin-degrading enzyme (IDE) as a modulator of microglial phenotypes in the context of Alzheimer’s disease and brain aging
Corraliza-Gómez, M., Bermejo, T., Lilue, J., Rodríguez-Iglesias, N., Valero, J., Cózar‐Castellano, I., Arranz, E. M., Sánchez, D., & Ganfornina, M. D. (2023) · Journal of Neuroinflammation · doi:10.1186/s12974-023-02914-7 · Cited by 39
“…cross-sectional studies in humans show such association in a bidirectional manner: T2D is over-represented in AD patients in comparison with controls [15–17] and, on the other hand, large population-based longitudinal studies show that T2D may significantly increase the risk of AD [18–21].”
Result
Neurocognitive impairment and comorbid depression in patients of diabetes mellitus
Solanki, R. K., Dubey, V., & Munshi, D. (2009) · International Journal of Diabetes in Developing Countries · doi:10.4103/0973-3930.54291 · Cited by 40
“The speciÞ c mechanism linking type 2 diabetes with cognitive deÞ cits has not been identiÞ ed; however, extraneuronal hyperglycemia, disturbed brain glucose metabolism, altered brain insulin signaling[8] and complications secondary to potential hypercortisolemia have all been implicated.”
Effect of age and glucoregulation on cognitive performance
Messier, C., Tsiakas, M., Gagnon, M., & Desrochers, A. (2010) · Journal of Clinical and Experimental Neuropsychology · doi:10.1080/13803390903540323 · Cited by 39
“…& De Leon, 2003; Kaplan et al., 2000), adults with impaired glucose tolerance (Vanhanen et al., 1997; Vanhanen et al., 1998), and in older adults with type 2 diabetes (Awad et al., 2004; Biessels et al., 2002; Stewart & Liolitsa, 1999; Strachan et al., 1997; Strachan, Frier, & Deary, 2003).”
Use of oral diabetes medications and the risk of incident dementia in US veterans aged ≥60 years with type 2 diabetes
Tang, X., Brinton, R. D., Chen, Z., Farland, L. V., Klimentidis, Y. C., Migrino, R. Q., Reaven, P. D., Rodgers, K. E., & Zhou, J. J. (2022) · BMJ Open Diabetes Research & Care · doi:10.1136/bmjdrc-2022-002894 · Cited by 38
The prevalence and predictors of cognitive impairment in type 2 diabetic population of Punjab, India
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“However, conclusions vary depending on the sampling strategy, study design, tests for cognition used, diabetes severity, and co-existing morbidities.([6,7]) Several association pathways of T2DM and cognitive decline have been established whereby some studies reported the association of diabetes with Alzheimer’s([8]) a…”
Background
Higher GABA concentration in the medial prefrontal cortex of Type 2 diabetes patients is associated with episodic memory dysfunction
Thielen, J.-W., Gancheva, S., Hong, D., Rankouhi, S. R., Chen, B., Apostolopoulou, M., Anadol, E., Roden, M., Norris, D. G., & Tendolkar, I. (2019) · Human Brain Mapping · doi:10.1002/hbm.24702 · Cited by 37
“In this regard, previous work has mainly investigated T2D related decline in single item memory, for example, word list learning (Jones et al., 2014; Stewart & Liolitsa, 1999), which is a different process with distinct neural substrates as compared to associative memory (Ranganath, 2010; Wang, Li,…”
Background
Accuracy of Self-Monitored Blood Glucose in Type 2 Diabetes
Kazlauskaite, R., Soni, S., Evans, A. T., Graham, K., & Fisher, B. (2009) · Diabetes Technology & Therapeutics · doi:10.1089/dia.2008.0111 · Cited by 39
“…of glucose self-monitoring might be adversely affected not only by the common conditions of depression and low literacy, but also by cognitive impaired from ‘‘diabetic encephalopathy,’’ 16 which was recently correlated with lesions on brain imaging by the Utrecht Diabetic Encephalopathy Group.”
Cerebral metabolism in streptozotocin-diabetic rats: an in vivo magnetic resonance spectroscopy study
Biessels, G. J., Braun, K. P. J., de Graaf, R. A., van Eijsden, P., Gispen, W. H., & Nicolay, K. (2001) · Diabetologia · doi:10.1007/s001250051625 · Cited by 37
MR spectroscopy of cerebral white matter in type 2 diabetes; no association with clinical variables and cognitive performance
Tiehuis, A. M., van der Meer, F. S., Mali, W. P. T. M., Pleizier, M., Biessels, G. J., Kappelle, J. L. J., & Luijten, P. R. (2009) · Neuroradiology · doi:10.1007/s00234-009-0598-4 · Cited by 37
“An important complication of DM2 is an increased risk for dementia [1].”
Background
Postural control and detection of slip/fall initiation in the elderly population
Kim, B., & Robinson, C. J. (2005) · Ergonomics · doi:10.1080/00140130500071028 · Cited by 36
“1991 , Stewart and Liolits 1999 , Gispen and Biessels 2000 ) have reported that diabetic people showed slower cognition, lack of proprioceptive feedback and higher magnitude of sway compared to the age-matched non-diabetic group.”
Association between Toxoplasma gondii seropositivity and memory function in nondemented older adults
Wyman, C. E., Gale, S. D., Hedges‐Muncy, A., Erickson, L. D., Wilson, E., & Hedges, D. W. (2017) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2017.01.018 · Cited by 36
“Introduction Multiple factors are associated with cognitive function and cognitive aging in older adults including sociodemographic variables, lifestyle, and diseases such as hypertension and diabetes (Gifford, et al., 2013, Stewart and Liolitsa, 1999, Zhang, et al., 2015).”
BackgroundResultInfluential
The Effects of Chromium Complex and Level on Glucose Metabolism and Memory Acquisition in Rats Fed High-Fat Diet
Şahin, K., Tuzcu, M., Orhan, C., Ağca, C. A., Şahin, N., Güvenç, M., Krejpcio, Z., Staniek, H., & Hayırlı, A. (2010) · Biological Trace Element Research · doi:10.1007/s12011-010-8905-9 · Cited by 36
“There are cross-sectional and prospective associations between type 2 diabetes and cognitive impairment, probably both for memory and executive functions [48, 49].”
Background
Nerve conduction velocity and evoked potential latencies in streptozotocin‐diabetic rats: effects of treatment with an angiotensin converting enzyme inhibitor
Manschot, S., Gispen, W. H., Kappelle, L. J., & Biessels, G. J. (2003) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.401 · Cited by 36
“Furthermore, recent epidemiological studies demonstrate an association between diabetes and vascular dementia as well as Alzheimer’s disease [3,5].”
Background
The Synergistic Effects of HIV, Diabetes, and Aging on Cognition
Vance, D. E., Fazeli, P. L., Dodson, J. E., Ackerman, M. L., Talley, M. H., & Appel, S. J. (2014) · Journal of Neuroscience Nursing · doi:10.1097/jnn.0000000000000074 · Cited by 36
“…of patients with type 2 diabetes when compared with the general population across all age groups (Noble, Manly, Schupf, Tang, & Luchsinger, 2012; Stewart & Liolitsa, 1999; Strachan, Deary, Ewing, & Frier, 1997), whereas longitudinal studies suggest a slow process of developing cognitive…”
Background
Cerebrovascular degradation of TRKB by MMP9 in the diabetic brain
Navaratna, D., Fan, X., Leung, W., Lok, J., Guo, S., Xing, C., Wang, X., & Lo, E. H. (2013) · Journal of Clinical Investigation · doi:10.1172/jci65767 · Cited by 32
The effects of glucose ingestion and glucose regulation on memory performance in older adults with mild cognitive impairment
Riby, L. M., Marriott, A., Bullock, R. M., Hancock, J., Smallwood, J., & McLaughlin, J. (2008) · European Journal of Clinical Nutrition · doi:10.1038/sj.ejcn.1602981 · Cited by 34
“Even with limited knowledge of how these factors interact, an elevated risk of both vascular dementia and AD exists for those with diabetes and associated disorders (Stewart and Liolitsa, 1999; Messier, 2005).”
Background
The effects of diabetes and/or peripheral neuropathy in detecting short postural perturbations in mature adults
Fulk, G. D., Robinson, C. J., Mondal, S., Storey, C. M., & Hollister, A. M. (2010) · Journal of NeuroEngineering and Rehabilitation · doi:10.1186/1743-0003-7-44 · Cited by 34
“Since our method of assessing psychophysical thresholds of balance requires attention, mild cognitive impairments secondary to diabetes could be involved [ 36 ,37].”
Method
Axonal and Dendritic Changes are Associated with Diabetic Encephalopathy in Rats: An Important Risk Factor for Alzheimer's Disease
Zhou, Y., Luo, Y., & Dai, J. (2013) · Journal of Alzheimer s Disease · doi:10.3233/jad-121762 · Cited by 33
“lesions, and cortical and subcortical atrophy [10–13].”
Caffeine, Diabetes, Cognition, and Dementia
Biessels, G. J. (2010) · Journal of Alzheimer s Disease · doi:10.3233/jad-2010-091228 · Cited by 34
“5) in populations with a mean age below 60 [28, 31].”
Chromium Picolinate Modulates Serotonergic Properties and Carbohydrate Metabolism in a Rat Model of Diabetes
Komorowski, J. R., Tuzcu, M., Şahin, N., Juturu, V., Orhan, C., Ulaş, M., & Şahin, K. (2012) · Biological Trace Element Research · doi:10.1007/s12011-012-9393-x · Cited by 32
“Stewart and Liolitsa [33] concluded that there is a cross-sectional and prospective association between type 2 and cognitive impairment, probably both for memory and executive functions.”
Background
Glucose tolerance and cognitive impairment in an elderly population
La, H., Keinanen-Kiukaanniemi, S. M., & Läärä, E. (2001) · Public Health · doi:10.1038/sj.ph.1900758 · Cited by 32
Increased spike broadening and slow afterhyperpolarization in CA1 pyramidal cells of streptozotocin-induced diabetic rats
Kamal, A., Artola, A., Biessels, G. J., Gispen, W. H., & Ramakers, G. M. J. (2003) · Neuroscience · doi:10.1016/s0306-4522(02)00874-6 · Cited by 32
A comparative study of reaction times between type II diabetics and non-diabetics
Richerson, S. J., Robinson, C. J., & Shum, J. (2005) · BioMedical Engineering OnLine · doi:10.1186/1475-925x-4-12 · Cited by 32
“In addition to the measured effects in these two studies, diabetes has also been shown to affect peripheral nerves in the somatosensory [7] and auditory system [8], slows psychomotor responses [9], and has cognitive effects on those individuals without proper metabolic control [ 10- 13 ], all of which may affect react…”
Background
Brain insulin resistance and Alzheimer’s disease: a systematic review
Andrade, L. J. D. O., de Oliveira, L. M., Bittencourt, A. M. V., Lourenço, L. G. D. C., & de Oliveira, G. C. M. (2024) · Dementia & Neuropsychologia · doi:10.1590/1980-5764-dn-2023-0032 · Cited by 35
“These studies reported that higher hemoglobin A1c levels were associated with more severe deficiencies, including memory impairments 53 .”
Background
AMPK γ2 subunit gene PRKAG2 polymorphism associated with cognitive impairment as well as diabetes in old age
Kim, E., Lee, S. H., Lee, K. S., Cheong, H., Namkoong, K., Hong, C. H., & Oh, B. H. (2011) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2011.07.005 · Cited by 31
The Brain-Gut-Islet Connection
Woods, S. C., Benoit, S. C., & Clegg, D. J. (2006) · Diabetes · doi:10.2337/db06-s015 · Cited by 30
Cognitive function in diabetic persons with peripheral neuropathy: a systematic review and meta-analysis
Palomo‐Osuna, J., Sola, H. D., Dueñas, M., Moral-Muñoz, J. A., & Failde, I. (2022) · Expert Review of Neurotherapeutics · doi:10.1080/14737175.2022.2048649 · Cited by 31
“tive impairment and dementia [48,49] and that fluctuations in blood sugar levels, insulin resistance and deposits of β-”
Background
Challenges in the epidemiological investigation of the relationships between physical activity, obesity, diabetes, dementia and depression
Brayne, C., Gao, L., & Matthews, F. E. (2005) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2005.09.030 · Cited by 30
Effectiveness of Yoga as the Public Health Intervention Module in the Management of Diabetes and Diabetes Associated Dementia in South East Asia: A Narrative Review
Bali, P., Kaur, N., Tiwari, A., Bammidi, S., Podder, V., Devi, C., Kumar, S., Sivapuram, M. S., Ghani, A., Modgil, S., et al. (2020) · Neuroepidemiology · doi:10.1159/000505816 · Cited by 32
Cognitive neuropsychology of Alzheimer's disease
Crutch, S. J. (2005) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.2005.063982 · Cited by 30
The Additive Effects of Type-2 Diabetes on Cognitive Function in Older Adults with Heart Failure
Alosco, M. L., Spitznagel, M. B., van Dulmen, M. H. M., Raz, N., Cohen, R. A., Sweet, L. H., Colbert, L. H., Josephson, R., Hughes, J. W., Rosneck, J., et al. (2012) · Cardiology Research and Practice · doi:10.1155/2012/348054 · Cited by 29
“It is likely that T2DM could be an important contributor to cognitive dysfunction in HF, as patients with T2DM are at increased risk for cognitive impairment independent of HF [18, 19].”
Background
Gait Parameters and Peripheral Neuropathy in Patients With Diabetes: A Meta-Analysis
Wang, Z., Peng, S., Zhang, H., Sun, H., & Hu, J. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.891356 · Cited by 32
“Epidemiologic studies have reported that diabetes is an independent risk factor for cognitive impairment (34, 35).”
Background
Which aspects of executive dysfunction influence ability to manage diabetes in older adults?
Munshi, M. N., Hayes, M., Iwata, I., Lee, Y., & Weinger, K. (2012) · Diabetic Medicine · doi:10.1111/j.1464-5491.2012.03606.x · Cited by 31
Testing covariates of Type 2 diabetes-cognition associations in older adults: Moderating or mediating effects?
McFall, G. P., Geall, B. P., Fischer, A. L., Dolcos, S. M., & Dixon, R. A. (2010) · Neuropsychology · doi:10.1037/a0019246 · Cited by 32
“When presenting with T2D, obesity (often measured as BMI) could affect cognitive performance through a variety of peripheral processes (e.g., sleep disturbance and apnoeic episodes; see McEwen, 2006; Stewart & Liolitsa, 1999).”
BackgroundInfluential
Glycemic load and risk of Alzheimer's disease.
Luchsinger, J. A., Tang, M. ‐., & Mayeux, R. P. (2007) · PubMed · Cited by 29
Diabetes mellitus and cognitive performance in older women
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Effects of the Ca2+ antagonist nimodipine on functional deficits in the peripheral and central nervous system of streptozotocin-diabetic rats
Biessels, G. J., ter Laak-Poort, M., Kamal, A., & Gispen, W. H. (2005) · Brain Research · doi:10.1016/j.brainres.2004.12.025 · Cited by 29
The Effects of Exercise Training on the Brain-Derived Neurotrophic Factor (BDNF) in the Patients with Type 2 Diabetes: A Systematic Review of the Randomized Controlled Trials
Jamali, A., Shahrbanian, S., & Tayebi, S. M. (2020) · Journal of Diabetes & Metabolic Disorders · doi:10.1007/s40200-020-00529-w · Cited by 30
Factors Associated with Cognitive Decline in Elderly Diabetics
Umegaki, H., Kawamura, T., Kawano, N., Umemura, T., Kanai, A., & Sano, T. (2011) · Dementia and Geriatric Cognitive Disorders Extra · doi:10.1159/000323188 · Cited by 28
Etanercept Improves Cognitive Performance and Increases eNOS and BDNF Expression During Experimental Vascular Dementia in Streptozotocin- induced Diabetes
Utkan, T., Yazır, Y., Karson, A., & Bayramgürler, D. (2015) · Current Neurovascular Research · doi:10.2174/1567202612666150311111340 · Cited by 27
“Second, DM is associated with moderate cognitive function impairments, and patients carry a high risk of dementia [44, 4, 1].”
Background
Neuro-Psychiatric Alterations in Patients with Diabetic Foot Syndrome
Navarro‐Flores, E., Pérez‐Ros, P., Martínez‐Arnau, F. M., Julían-Rochina, I., & Cauli, O. (2019) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/1871527318666191002094406 · Cited by 28
Mild Cognitive Impairment and Donepezil Impact Mitochondrial Respiratory Capacity in Skeletal Muscle
Morris, J. K., McCoin, C. S., Fuller, K. N. Z., John, C. S., Wilkins, H., Green, Z. D., Wang, X., Sharma, P., Burns, J. M., Vidoni, E. D., et al. (2021) · Function · doi:10.1093/function/zqab045 · Cited by 26
Impairment of executive cognitive control in type 2 diabetes, and its effects on health-related behavior and use of health services
Tran, D., Baxter, J., Hamman, R. F., & Grigsby, J. (2013) · Journal of Behavioral Medicine · doi:10.1007/s10865-013-9499-4 · Cited by 31
“For example, some reports have noted a link between diabetes and both vascular dementia and Alzheimer’s disease (AD; Bruce et al., 2001; Stewart & Liolitsa, 1999), possibly in conjunction with an increase in the prevalence of cerebrovascular disease (CVD) among diabetic persons.”
Relationship between the diagnostic components of metabolic syndrome (MS) and cognition by ApoE genotype in the elderly
Lee, K. S., Jang, Y., Chung, Y. K., Chung, J. H., Oh, B. H., & Hong, C. H. (2009) · Archives of Gerontology and Geriatrics · doi:10.1016/j.archger.2009.01.014 · Cited by 27
“, 2005), diabetes (Elias et al., 1997; Stewart and Liolitsa, 1999), dyslipidemia (Isbir et al.”
Alzheimer’s Disease: Halothane Induces Aβ Peptide to Oligomeric Form—Solution NMR Studies
Mandal, P. K., Pettegrew, J. W., McKeag, D. W., & Mandal, R. (2006) · Neurochemical Research · doi:10.1007/s11064-006-9092-0 · Cited by 27
“These risk factors for AD are age [8], low educational attainment [9], gender (AD affects more women than men) [10], head injury [11], hypertension [12], cardiovascular disease [13] and diabetes [14].”
Background
Retracted
Effects of improved glycaemic control maintained for 3 months on cognitive function in patients with Type 2 diabetes
Mussell, M., Hewer, W., Kulzer, B., Bergis, K., & Rist, F. (2004) · Diabetic Medicine · doi:10.1111/j.1464-5491.2004.01322.x · Cited by 27
Vascular Risk Factors and Alzheimer's Disease
Stewart, R. J., Prince, M. J., & MANN, A. H. (1999) · Australian & New Zealand Journal of Psychiatry · doi:10.1046/j.1440-1614.1999.00657.x · Cited by 26
“Recent evidence has suggested potentially important similarities between the intracellular pathways of insulin metabolism and those involved in the phosphorylation of tau protein (underlying neurofibrillary tangle formation in AD), raising the possibility of common, possibly genetically determined, abnormalities under…”
BackgroundSelf-citation
Folic Acid Reduces Tau Phosphorylation by Regulating PP2A Methylation in Streptozotocin-Induced Diabetic Mice
Zheng, M., Zou, C., Li, M., Huang, G., Gao, Y., & Liu, H. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18040861 · Cited by 27
“A number of cross-sectional and longitudinal studies have examined the association between type II diabetes mellitus (DM) and cognitive impairment [4,5], mild cognitive impairment (MCI), and dementia [6].”
Background
Appropriate Application of Evidence to the Care of Elderly Patients with Diabetes
Huang, E. S. (2007) · Current Diabetes Reviews · doi:10.2174/1573399810703040260 · Cited by 26
“Other geriatric syndromes, such as depression [31], cognitive impairment [32], urinary incontinence [33], and chronic pain [34] are more common among elderly patients with diabetes and may be of great importance to the patient.”
Background
Vascular and Endothelial Function in Youth with Type 2 Diabetes Mellitus
SHAH, A. S., & Urbina, E. M. (2017) · Current Diabetes Reports · doi:10.1007/s11892-017-0869-0 · Cited by 26
Cognitive Functioning and Self-Management in Older People With Diabetes
Asimakopoulou, K. G., & Hampson, S. E. (2002) · Diabetes Spectrum · doi:10.2337/diaspect.15.2.116 · Cited by 26
RAGE-NF-κB-PPARγ Signaling is Involved in AGEs-Induced Upregulation of Amyloid-β Influx Transport in an In Vitro BBB Model
Chen, F., Ghosh, A., Hu, M. Y., Long, Y., Sun, H., Kong, L., Hong, H., & Tang, S. (2017) · Neurotoxicity Research · doi:10.1007/s12640-017-9784-z · Cited by 26
“A growing number of clinical and epidemiological evidences correlate a strong connection between type 2 diabetes (T2D) and Alzheimer’s disease (AD) (Arvanitakis et al. 2004; Sanz et al. 2012; Stewart and Liolitsa 1999).”
Background
Heat therapy: possible benefits for cognitive function and the aging brain
Schulze, A. T. V., Deng, F., Morris, J. K., & Geiger, P. C. (2020) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00168.2020 · Cited by 26
“Mitochondrial dysfunction in skeletal muscle has also been heavily studied as a primary cause of whole body insulin resistance (41, 72, 127), a recognized risk factor for AD (9, 24, 60, 74, 80, 93, 97, 100, 110, 119, 123, 124).”
Background
Exploring the Chemical Profiles and Biological Values of Two Spondias Species (S. dulcis and S. mombin): Valuable Sources of Bioactive Natural Products
Sinan, K. I., Zengin, G., Zheleva‐Dimitrova, D., Gevrenova, R., Picot-Allain, M. C. N., Dall’Acqua, S., Behl, T., Goh, B. H., Tang, S. Y., & Mahomoodally, M. F. (2021) · Antioxidants · doi:10.3390/antiox10111771 · Cited by 25
Fleshing out the amyloid cascade hypothesis: the molecular biology of Alzheimer's disease
Lovestone, S. (2000) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2000.2.2/slovestone · Cited by 28
“However, in cells, we demonstrated that it is only glycogen synthase kinase–3 (GSK-3) that is able to phosphorylate tau readily at epitopes also phosphorylated in AD.57,58 Simultaneously, Ishiguro and colleagues purified a kinase from brain that readily phosphorylated tau, which they named tau protein kinase 1 (TPK1).…”
BackgroundInfluential
Neuroanatomical correlates of executive functioning in depressed adults with type 2 diabetes
Watari, K. F., Elderkin‐Thompson, V., Ajilore, O., Haroon, E., Darwin, C. H., Pham, D. L., & Kumar, A. (2008) · Journal of Clinical and Experimental Neuropsychology · doi:10.1080/13803390701440486 · Cited by 25
“…Gagnon, & Messier, 2004), specifically in the domains of verbal memory, executive functioning and psychomotor speed; however, methodological and study design differences have resulted in tentative conclusions (Hassing et al., 2004; Stewart & Liolitsa, 1999; Strachan, Deary, Ewing, & Frier, 1997).”
Result
Glucose regulation is associated with cognitive performance in young nondiabetic adults
Messier, C., Awad, N., Gagnon, M., Desrochers, A., & Tsiakas, M. (2011) · Behavioural Brain Research · doi:10.1016/j.bbr.2011.03.023 · Cited by 25
Synaptic plasticity in the diabetic brain: advanced aging?
Artola, A., Kamal, A., Ramakers, G., Gardoni, F., di Luca, M., Biessels, G., Cattabeni, F., & Gispen, W. (2002) · Progress in Brain Research · doi:10.1016/s0079-6123(02)38084-1 · Cited by 28
Management of Diabetes Mellitus in Older Adults: Are National Guidelines Appropriate?
Blaum, C. S. (2002) · Journal of the American Geriatrics Society · doi:10.1046/j.1532-5415.2002.50130.x · Cited by 25
Effects of demographic variables and health status on brief vocabulary measures in Greek
Simos, P. G., Kasselimis, D. S., & Mouzaki, A. (2010) · Aphasiology · doi:10.1080/02687038.2010.512120 · Cited by 24
“Finally, the study did not provide detailed information on several important variables in participants who reported suffering from Type-II diabetes, namely the duration of the disease, degree of compliance with medication and diet regimes, overall success in controlling glucose levels, and presence of other vascular r…”
Background
Is There Inflammatory Synergy in Type II Diabetes Mellitus and Alzheimer’s Disease?
Lue, L., Andrade, C., Sabbagh, M. N., & Walker, D. G. (2012) · International Journal of Alzheimer s Disease · doi:10.1155/2012/918680 · Cited by 24
Glucoregulation has Greater Impact on Cognitive Performance than Macro-vascular Disease in Men with type 2 Diabetes: Data from the Caerphilly Study
Gallacher, J., Pickering, J. E., Elwood, P. C., Bayer, A. J., YARNELL, J. W. G., & Ben‐Shlomo, Y. (2005) · European Journal of Epidemiology · doi:10.1007/s10654-005-2146-9 · Cited by 24
“Hyperglycemic related vascular and neurological complications of diabetes have led some to suggest that vascular and neurological pathology are the mechanism by diabetes is related to cognitive impairment [22, 23].”
Background
Education and the Association Between Vascular Risk Factors and Cognitive Function: A Cross-Sectional Study in Older Koreans With Cognitive Impairment
Stewart, R. J., Kim, J., Shin, I., & Yoon, J. (2003) · International Psychogeriatrics · doi:10.1017/s1041610203008731 · Cited by 24
Self-citation
Clinical and Genetic Aspects of Epilepsy
Heron, S., & Mulley, J. (2011) · InTech eBooks · doi:10.5772/1138 · Cited by 24

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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