Cognitive decline and dementia in diabetes mellitus: mechanisms and clinical implications
Open accessAbstract
Cognitive dysfunction is increasingly recognized as an important comorbidity of diabetes mellitus. Different stages of diabetes-associated cognitive dysfunction exist, each with different cognitive features, affected age groups and prognoses and probably with different underlying mechanisms. Relatively subtle, slowly progressive cognitive decrements occur in all age groups. More severe stages, particularly mild cognitive impairment and dementia, with progressive deficits, occur primarily in older individuals (>65 years of age). Patients in the latter group are the most relevant for patient management and are the focus of this Review. Here, we review the evolving insights from studies on risk factors, brain imaging and neuropathology, which provide important clues on mechanisms of both the subtle cognitive decrements and the more severe stages of cognitive dysfunction. In the majority of patients, the cognitive phenotype is probably defined by multiple aetiologies. Although both the risk of clinically diagnosed Alzheimer disease and that of vascular dementia is increased in association with diabetes, the cerebral burden of the prototypical pathologies of Alzheimer disease (such as neurofibrillary tangles and neuritic plaques) is not. A major challenge for researchers is to pinpoint from the spectrum of diabetes-related disease processes those that affect the brain and contribute to development of dementia beyond the pathologies of Alzheimer disease. Observations from experimental models can help to meet that challenge, but this requires further improving the synergy between experimental and clinical scientists. The development of targeted treatment and preventive strategies will therefore depend on these translational efforts.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Self-monitoring and judgments about symptoms, physical status, and needed alterations to self-management behaviors are mediated by executive function.
“Thus, monitoring of cognitive capacity of individuals is recommended, particularly regarding their ability to self-monitor and make judgments about their symptoms, physical status, and needed alterations to their self-management behaviors, all of which are mediated by executive function (427).”
From 5. Facilitating Positive Health Behaviors and Well-being to Improve Health Outcomes:<i>Standards of Care in Diabetes—2023</i> (2023) · cites this paper as [427]
Diagnosis of dementia is more prevalent among people with diabetes, both type 1 and type 2.
“Diagnosis of dementia is also more prevalent among people with diabetes, both type 1 and type 2 (427).”
From 5. Facilitating Positive Health Behaviors and Well-being to Improve Health Outcomes:<i>Standards of Care in Diabetes—2023</i> (2023) · cites this paper as [427]
Cites
International Diabetes Federation 2017
Carracher, A. M., Marathe, P. H., & Close, K. L. (2018) · Journal of Diabetes · doi:10.1111/1753-0407.12644 · Cited by 13,369 · see citing works
Standards of Medical Care in Diabetes
Power, D. V. (2006) · Diabetes Care · doi:10.2337/diacare.29.02.06.dc05-1593 · Cited by 8,672 · see citing works
Mild cognitive impairment as a diagnostic entity
Petersen, R. C. (2004) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2004.01388.x · Cited by 7,864 · see citing works
Wardlaw, J. M., Smith, E. E., Biessels, G. J., Cordonnier, C., Fazekas, F., Frayne, R., Lindley, R. I., O'Brien, J. T., Barkhof, F., Benavente, O. R., et al. (2013) · The Lancet Neurology · doi:10.1016/s1474-4422(13)70124-8 · Cited by 5,560 · see citing works
Self-citationThe global prevalence of dementia: a systematic review and metaanalysis.
Prince, M., Bryce, R., Albanese, E., Wimo, A., Ribeiro, W., & Ferri, C. P. (2013) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2012.11.007 · Cited by 4,941 · see citing works
Scheltens, P., Blennow, K., Breteler, M. M. B., de Strooper, B., Frisoni, G. B., Salloway, S., & Van der Flier, W. M. (2016) · The Lancet · doi:10.1016/s0140-6736(15)01124-1 · Cited by 3,125 · see citing works
The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease
Sevigny, J., Chiao, P., Bussière, T., Weinreb, P. H., Williams, L., Maier, M., Dunstan, R., Salloway, S., Chen, T., Ling, Y., et al. (2016) · Nature · doi:10.1038/nature19323 · Cited by 3,059 · see citing works
Mendelson, G. (1995) · Australian & New Zealand Journal of Psychiatry · doi:10.3109/00048679509064964 · Cited by 2,592 · see citing works
Potential for primary prevention of Alzheimer's disease: an analysis of population-based data
Norton, S., Matthews, F. E., Barnes, D. E., Yaffe, K., & Brayne, C. (2014) · The Lancet Neurology · doi:10.1016/s1474-4422(14)70136-x · Cited by 2,466 · see citing works
Risk of dementia in diabetes mellitus: a systematic review
Biessels, G. J., Staekenborg, S., Brunner, E., Brayne, C., & Scheltens, P. (2006) · The Lancet Neurology · doi:10.1016/s1474-4422(05)70284-2 · Cited by 2,187 · see citing works
Self-citationRevising the definition of Alzheimer's disease: a new lexicon
Dubois, B., Feldman, H. H., Jacova, C., Cummings, J. L., DeKosky, S. T., Barberger-Gateau, P., Delacourte, A., Frisoni, G., Fox, N. C., Galasko, D., et al. (2010) · The Lancet Neurology · doi:10.1016/s1474-4422(10)70223-4 · Cited by 1,869 · see citing works
The Pathobiology of Vascular Dementia
Iadecola, C. (2013) · Neuron · doi:10.1016/j.neuron.2013.10.008 · Cited by 1,857 · see citing works
Pathophysiology and treatment of type 2 diabetes: perspectives on the past, present, and future
Kahn, S. E., Cooper, M. E., & Del Prato, S. (2014) · The Lancet · doi:10.1016/s0140-6736(13)62154-6 · Cited by 1,743 · see citing works
Mechanisms of sporadic cerebral small vessel disease: insights from neuroimaging
Wardlaw, J. M., Smith, C., & Dichgans, M. (2013) · The Lancet Neurology · doi:10.1016/s1474-4422(13)70060-7 · Cited by 1,657 · see citing works
Brain insulin resistance in type 2 diabetes and Alzheimer disease: concepts and conundrums
Arnold, S. E., Arvanitakis, Z., Macauley-Rambach, S. L., Koenig, A. M., Wang, H.-Y., Ahima, R. S., Craft, S., Gandy, S., Buettner, C., Stoeckel, L. E., et al. (2018) · Nature Reviews Neurology · doi:10.1038/nrneurol.2017.185 · Cited by 1,597 · see citing works
Islet Amyloid Polypeptide, Islet Amyloid, and Diabetes Mellitus
Westermark, P., Andersson, A., & Westermark, G. T. (2011) · Physiological Reviews · doi:10.1152/physrev.00042.2009 · Cited by 1,044 · see citing works
Basta, G. (2004) · Cardiovascular Research · doi:10.1016/j.cardiores.2004.05.001 · Cited by 996 · see citing works
Glucose Levels and Risk of Dementia
Crane, P. K., Walker, R., Hubbard, R. A., Li, G., Nathan, D. M., Zheng, H., Haneuse, S., Craft, S., Montine, T. J., Kahn, S. E., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1215740 · Cited by 929 · see citing works
What are White Matter Hyperintensities Made of?
Wardlaw, J. M., Hernández, M. C. V., & Maniega, S. M. (2015) · Journal of the American Heart Association · doi:10.1161/jaha.114.001140 · Cited by 902 · see citing works
The Effects of Type 1 Diabetes on Cognitive Performance
Brands, A. M. A., Biessels, G. J., de Haan, E. H. F., Kappelle, L. J., & Kessels, R. P. C. (2005) · Diabetes Care · doi:10.2337/diacare.28.3.726 · Cited by 738 · see citing works
Self-citationDiabetes mellitus and risk of dementia: A meta‐analysis of prospective observational studies
Gudala, K., Bansal, D., Schifano, F., & Bhansali, A. (2013) · Journal of Diabetes Investigation · doi:10.1111/jdi.12087 · Cited by 727 · see citing works
Chatterjee, S., Peters, S. A. E., Woodward, M., Mejia Arango, S., Batty, G. D., Beckett, N., Beiser, A., Borenstein, A. R., Crane, P. K., Haan, M., et al. (2016) · Diabetes Care · doi:10.2337/dc15-1588 · Cited by 711 · see citing works
Association Between Midlife Vascular Risk Factors and Estimated Brain Amyloid Deposition
Gottesman, R. F., Schneider, A. L. C., Zhou, Y., Coresh, J., Green, E., Gupta, N., Knopman, D. S., Mintz, A., Rahmim, A., Sharrett, A. R., et al. (2017) · JAMA · doi:10.1001/jama.2017.3090 · Cited by 650 · see citing works
Cognition and diabetes: a lifespan perspective
Biessels, G. J., Deary, I. J., & Ryan, C. M. (2008) · The Lancet Neurology · doi:10.1016/s1474-4422(08)70021-8 · Cited by 646 · see citing works
Self-citationLong-term effect of diabetes and its treatment on cognitive function
(2007) · New England Journal of Medicine · doi:10.1056/nejmoa066397 · Cited by 646 · see citing works
Diabetic hyperglycaemia activates CaMKII and arrhythmias by O-linked glycosylation
Erickson, J. R., Pereira, L., Wang, L., Han, G., Ferguson, A., Dao, K., Copeland, R. J., Despa, F., Hart, G. W., Ripplinger, C. M., et al. (2013) · Nature · doi:10.1038/nature12537 · Cited by 601 · see citing works
Self-citationRelation of diabetes to mild cognitive impairment
Luchsinger, J. A., Reitz, C., Patel, B., Tang, M.-X., Manly, J. J., & Mayeux, R. (2007) · Archives of Neurology · doi:10.1001/archneur.64.4.570 · Cited by 592 · see citing works
Arvanitakis, Z., Capuano, A. W., Leurgans, S. E., Bennett, D. A., & Schneider, J. A. (2016) · The Lancet Neurology · doi:10.1016/s1474-4422(16)30029-1 · Cited by 581 · see citing works
Cooper, C., Sommerlad, A., Lyketsos, C. G., & Livingston, G. (2015) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2014.14070878 · Cited by 570 · see citing works
Berendsen, A. A. M., Kang, J. H., van de Rest, O., Jankovic, N., Kampman, E., Jong, J. C. K., Franco, O. H., Ikram, M. A., Pikhart, H., Nilsson, L. M., et al. (2017) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000464269 · Cited by 565 · see citing works
Biessels, G. J., Strachan, M. W. J., Visseren, F. L. J., Kappelle, L. J., & Whitmer, R. A. (2013) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(13)70088-3 · Cited by 555 · see citing works
Self-citationHippocampal insulin resistance and cognitive dysfunction
Biessels, G. J., & Reagan, L. P. (2015) · Nature reviews. Neuroscience · doi:10.1038/nrn4019 · Cited by 536 · see citing works
Self-citationTakeda, S., Sato, N., Uchio‐Yamada, K., Sawada, K., Kunieda, T., Takeuchi, D., Kurinami, H., Shinohara, M., Rakugi, H., & Morishita, R. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1000645107 · Cited by 506 · see citing works
Impact of Metabolic Syndrome on Cognition and Brain: A Selected Review of the Literature
Yates, K. F., Sweat, V., Yau, P. L., Turchiano, M. M., & Convit, A. (2012) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.112.252759 · Cited by 444 · see citing works
Vascular Complications of Diabetes
Beckman, J. A., & Creager, M. A. (2016) · Circulation Research · doi:10.1161/circresaha.115.306884 · Cited by 416 · see citing works
Vascular risk factors and dementia: How to move forward?
Viswanathan, A., Rocca, W. A., & Tzourio, C. (2009) · Neurology · doi:10.1212/01.wnl.0000341271.90478.8e · Cited by 414 · see citing works
Smith, E. E., Saposnik, G., Biessels, G. J., Doubal, F. N., Fornage, M., Gorelick, P. B., Greenberg, S. M., Higashida, R. T., Kasner, S. E., & Seshadri, S. (2017) · Stroke · doi:10.1161/str.0000000000000116 · Cited by 404 · see citing works
Self-citationCognitive function in patients with diabetes mellitus: guidance for daily care
Koekkoek, P. S., Kappelle, L. J., van den Berg, E., Rutten, G. E. H. M., & Biessels, G. J. (2015) · The Lancet Neurology · doi:10.1016/s1474-4422(14)70249-2 · Cited by 401 · see citing works
Self-citationGlucose regulation, cognition, and brain MRI in type 2 diabetes: a systematic review
Geijselaers, S. L. C., Sep, S. J. S., Stehouwer, C. D. A., & Biessels, G. J. (2014) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(14)70148-2 · Cited by 378 · see citing works
Self-citationAn updated meta-analysis of cohort studies: Diabetes and risk of Alzheimer’s disease
Zhang, J., Chen, C., Hua, S., Liao, H., Wang, M., Xiong, Y., & Cao, F. (2017) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2016.10.024 · Cited by 376 · see citing works
Palta, P., Schneider, A. L. C., Biessels, G. J., Touradji, P., & Hill-Briggs, F. (2014) · Journal of the International Neuropsychological Society · doi:10.1017/s1355617713001483 · Cited by 364 · see citing works
Self-citationLi, J., Tan, L., Wang, H.-F., Tan, M., Tan, L., Xu, W., Zhao, Q., Wang, J., Jiang, T., & Yu, J. (2015) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2014-310095 · Cited by 360 · see citing works
Amylin deposition in the brain: A second amyloid in Alzheimer disease?
Jackson, K., Barisone, G. A., Dı́az, E., Jin, L., DeCarli, C. S., & Despa, F. (2013) · Annals of Neurology · doi:10.1002/ana.23956 · Cited by 340 · see citing works
Self-citationde la Monte, S. M., Tong, M., Lester-Coll, N. H., Plater, M. E., & Wands, J. R. (2006) · Journal of Alzheimer s Disease · doi:10.3233/jad-2006-10113 · Cited by 324 · see citing works
Diabetes, glucose control, and 9-year cognitive decline among older adults without dementia
Yaffe, K., Falvey, C., Hamilton, N., Schwartz, A. V., Simonsick, E. M., Satterfield, S., Cauley, J. A., Rosano, C., Launer, L. J., Strotmeyer, E. S., et al. (2012) · Archives of Neurology · doi:10.1001/archneurol.2012.1117 · Cited by 313 · see citing works
Detection, risk factors, and functional consequences of cerebral microinfarcts
van Veluw, S. J., Shih, A. Y., Smith, E. E., Chen, C., Schneider, J. A., Wardlaw, J. M., Greenberg, S. M., & Biessels, G. J. (2017) · The Lancet Neurology · doi:10.1016/s1474-4422(17)30196-5 · Cited by 306 · see citing works
Self-citationType 2 diabetes mellitus and biomarkers of neurodegeneration
Moran, C., Beare, R. J., Phan, T. G., Bruce, D. G., Callisaya, M. L., & Srikanth, V. K. (2015) · Neurology · doi:10.1212/wnl.0000000000001982 · Cited by 298 · see citing works
Brain Changes Underlying Cognitive Dysfunction in Diabetes: What Can We Learn From MRI?
Biessels, G. J., & Reijmer, Y. D. (2014) · Diabetes · doi:10.2337/db14-0348 · Cited by 296 · see citing works
Self-citationIn Vivo Seeding and Cross-Seeding of Localized Amyloidosis
Oskarsson, M. E., Paulsson, J. F., Schultz, S. W., Ingelsson, M., Westermark, P., & Westermark, G. T. (2015) · American Journal Of Pathology · doi:10.1016/j.ajpath.2014.11.016 · Cited by 281 · see citing works
Diabetes is related to cerebral infarction but not to AD pathology in older persons
Arvanitakis, Z., Schneider, J. A., Wilson, R. S., Li, Y., Arnold, S. E., Wang, Z., & Bennett, D. A. (2006) · Neurology · doi:10.1212/01.wnl.0000247053.45483.4e · Cited by 280 · see citing works
de Bruijn, R. F. A. G., Bos, M. J., Portegies, M. L. P., Albert Hofman, D., Franco, O. H., Koudstaal, P. J., & Ikram, M. A. (2015) · BMC Medicine · doi:10.1186/s12916-015-0377-5 · Cited by 274 · see citing works
Sastre, A. A., Vernooij, R. W. M., Harmand, M. G., & Martínez, G. (2017) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd003804.pub2 · Cited by 271 · see citing works
Alzheimer-Like Changes in Rat Models of Spontaneous Diabetes
Li, Z.-G., Zhang, W., & Sima, A. A. F. (2007) · Diabetes · doi:10.2337/db07-0171 · Cited by 265 · see citing works
Insulin Resistance and Alzheimer’s Disease: Bioenergetic Linkages
Neth, B., & Craft, S. (2017) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2017.00345 · Cited by 263 · see citing works
Cognitive dysfunction in older adults with diabetes: what a clinician needs to know
Munshi, M. N. (2017) · Diabetes Care · doi:10.2337/dc16-1229 · Cited by 255 · see citing works
The neurovascular link in health and disease: molecular mechanisms and therapeutic implications
Quaegebeur, A., Lange, C., & Carmeliet, P. (2011) · Neuron · doi:10.1016/j.neuron.2011.07.013 · Cited by 247 · see citing works
Exalto, L. G., Biessels, G. J., Karter, A. J., Huang, E. S., Katon, W. J., Minkoff, J. R., & Whitmer, R. A. (2013) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(13)70048-2 · Cited by 244 · see citing works
Self-citationfor the ADVANCE Collaborative group, de Galan, B. E., Zoungas, S., Chalmers, J., Anderson, C., Dufouil, C., Pillai, A., Cooper, M., Grobbee, D. E., Hackett, M., et al. (2009) · Diabetologia · doi:10.1007/s00125-009-1484-7 · Cited by 243 · see citing works
Wang, Z., Wang, B., Yang, L., Guo, Q., Aithmitti, N., Songyang, Z., & Zheng, H. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.2132-09.2009 · Cited by 242 · see citing works
Marks, D. R., Tucker, K., Cavallin, M. A., Mast, T. G., & Fadool, D. A. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.1350-09.2009 · Cited by 242 · see citing works
Increased Tau Phosphorylation and Cleavage in Mouse Models of Type 1 and Type 2 Diabetes
Kim, B., Backus, C., Oh, S., Hayes, J. M., & Feldman, E. L. (2009) · Endocrinology · doi:10.1210/en.2009-0695 · Cited by 241 · see citing works
Insulin Dysfunction InducesIn VivoTau Hyperphosphorylation through Distinct Mechanisms
Planel, E., Tatebayashi, Y., Miyasaka, T., Liu, L., Wang, L., Herman, M., Yu, W. H., Luchsinger, J. A., Wadzinski, B. E., Duff, K., et al. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.3949-07.2007 · Cited by 238 · see citing works
Janelidze, S., Hertze, J., Nägga, K., Nilsson, K., Nilsson, C., Wennström, M., van Westen, D., Blennow, K., Zetterberg, H., & Hansson, O. (2017) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2016.11.017 · Cited by 237 · see citing works
Diabetes is associated with cerebrovascular but not Alzheimer's disease neuropathology
Abner, E. L., Nelson, P. T., Kryscio, R. J., Schmitt, F. A., Fardo, D. W., Woltjer, R. L., Cairns, N. J., Yu, L., Dodge, H. H., Xiong, C., et al. (2016) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2015.12.006 · Cited by 233 · see citing works
Moreno‐González, I., Edwards, G. A., Salvadores, N., Shahnawaz, M., Díaz‐Espinoza, R., & Soto, C. A. (2017) · Molecular Psychiatry · doi:10.1038/mp.2016.230 · Cited by 210 · see citing works
Young-Pearse, T. L., Chen, A. C., Chang, R., Marquez, C., & Selkoe, D. J. (2008) · Neural Development · doi:10.1186/1749-8104-3-15 · Cited by 210 · see citing works
Association of diabetes with amnestic and nonamnestic mild cognitive impairment
Roberts, R. O., Knopman, D. S., Geda, Y. E., Cha, R. H., Pankratz, V. S., Baertlein, L. A., Boeve, B. F., Tangalos, E. G., Ivnik, R. J., Mielke, M. M., et al. (2013) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2013.01.001 · Cited by 203 · see citing works
(2016) · Diabetes Care · doi:10.2337/dc17-s001 · Cited by 200 · see citing works
Clodfelder‐Miller, B., Zmijewska, A. A., Johnson, G. V. W., & Jope, R. S. (2006) · Diabetes · doi:10.2337/db06-0485 · Cited by 185 · see citing works
Feinkohl, I., Price, J. F., Strachan, M. W. J., & Frier, B. M. (2015) · Alzheimer s Research & Therapy · doi:10.1186/s13195-015-0130-5 · Cited by 183 · see citing works
Age, vascular health, and Alzheimer disease biomarkers in an elderly sample
Vemuri, P., Lesnick, T. G., Przybelski, S. A., Knopman, D. S., Lowe, V. J., Graff‐Radford, J., Roberts, R. O., Mielke, M. M., Machulda, M. M., Petersen, R. C., et al. (2017) · Annals of Neurology · doi:10.1002/ana.25071 · Cited by 183 · see citing works
Human cerebral neuropathology of Type 2 diabetes mellitus
Nelson, P. T., Smith, C. D., Abner, E. L., Schmitt, F. A., Scheff, S. W., Davis, G. J., Keller, J. N., Jicha, G. A., Davis, D. G., Wang, W., et al. (2008) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2008.08.005 · Cited by 177 · see citing works
The impact of diabetes on cognition: What can be learned from rodent models?
Biessels, G. J., & Gispen, W. H. (2005) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2005.08.015 · Cited by 172 · see citing works
Self-citationHeyward, F. D., Walton, R. G., Carle, M. S., Coleman, M. A., Garvey, W. T., & Sweatt, J. D. (2012) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2012.04.005 · Cited by 165 · see citing works
Metformin vs sulfonylurea use and risk of dementia in US veterans aged ≥65 years with diabetes
Orkaby, A. R., Cho, K., Cormack, J. B., GAGNON, D. R., & Driver, J. A. (2017) · Neurology · doi:10.1212/wnl.0000000000004586 · Cited by 159 · see citing works
Devi, L., Alldred, M. J., Ginsberg, S. D., & Ohno, M. (2012) · PLoS ONE · doi:10.1371/journal.pone.0032792 · Cited by 155 · see citing works
Diabetes drugs and neurological disorders: new views and therapeutic possibilities
Patrone, C., Eriksson, O., & Lindholm, D. (2013) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(13)70125-6 · Cited by 154 · see citing works
Puig, K. L., Floden, A. M., Adhikari, R., Golovko, M. Y., & Combs, C. K. (2012) · PLoS ONE · doi:10.1371/journal.pone.0030378 · Cited by 152 · see citing works
Neuroinflammation and neurologic deficits in diabetes linked to brain accumulation of amylin
Srodulski, S. J., Sharma, S., Bachstetter, A. D., Brelsfoard, J., Pascual, C., Xie, X., Saatman, K. E., Eldik, L. J. V., & Despa, F. (2014) · Molecular Neurodegeneration · doi:10.1186/1750-1326-9-30 · Cited by 152 · see citing works
Self-citationIslet Amyloid Polypeptide (IAPP) Transgenic Rodents as Models for Type 2 Diabetes
Matveyenko, A. V., & Butler, P. C. (2006) · ILAR Journal · doi:10.1093/ilar.47.3.225 · Cited by 150 · see citing works
Differential central pathology and cognitive impairment in pre-diabetic and diabetic mice
Ramos‐Rodríguez, J. J., Ortiz, O., Jiménez-Palomares, M., Kay, K. R., Berrocoso, E., Murillo-Carretero, M. I., Perdomo, G., Spires‐Jones, T. L., Cózar‐Castellano, I., Lechuga-Sancho, A. M., et al. (2013) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2013.05.010 · Cited by 146 · see citing works
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 142 · see citing works
Hyperamylinemia Contributes to Cardiac Dysfunction in Obesity and Diabetes
Despa, S. I., Margulies, K. B., Chen, L., Knowlton, A. A., Havel, P. J., Taegtmeyer, H., Bers, D. M., & Despa, F. (2012) · Circulation Research · doi:10.1161/circresaha.111.258285 · Cited by 137 · see citing works
Self-citationNeurocognitive consequences of diabetes.
Ryan, C. M., van Duinkerken, E., & Rosano, C. (2016) · American Psychologist · doi:10.1037/a0040455 · Cited by 136 · see citing works
Diabetes, markers of brain pathology and cognitive function
Qiu, C., Sigurdsson, S. O., Zhang, Q., Jónsdóttir, M. K., Kjartansson, Ó., Eiríksdóttir, G., Garcia, M. E., Harris, T. B., van Buchem, M. A., Gudnason, V. G., et al. (2013) · Annals of Neurology · doi:10.1002/ana.24063 · Cited by 134 · see citing works
Clinically Relevant Cognitive Impairment in Middle-Aged Adults With Childhood-Onset Type 1 Diabetes
Nunley, K. A., Rosano, C., Ryan, C. M., Jennings, J. R., Aizenstein, H. J., Zgibor, J. C., Costacou, T., Boudreau, R. M., Miller, R. G., Orchard, T. J., et al. (2015) · Diabetes Care · doi:10.2337/dc15-0041 · Cited by 130 · see citing works
Brain imaging in type 2 diabetes
Brundel, M., Kappelle, L. J., & Biessels, G. J. (2014) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2014.01.023 · Cited by 127 · see citing works
Self-citationvan 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 · see citing works
Self-citationRisk of Dementia in Seniors With Newly Diagnosed Diabetes: A Population-Based Study
Haroon, N. N., Austin, P. C., Shah, B. R., Wu, J., Gill, S. S., & Booth, G. L. (2015) · Diabetes Care · doi:10.2337/dc15-0491 · Cited by 126 · see citing works
A Meta-Analysis of Cognitive Functioning in Nondemented Adults with Type 2 Diabetes Mellitus
Monette, M., Baird, A. D., & Jackson, D. L. (2014) · Canadian Journal of Diabetes · doi:10.1016/j.jcjd.2014.01.014 · Cited by 115 · see citing works
Glucose Peaks and the Risk of Dementia and 20-Year Cognitive Decline
Rawlings, A. M., Sharrett, A. R., Mosley, T. H., Ballew, S. H., Deal, J. A., & Selvin, E. (2017) · Diabetes Care · doi:10.2337/dc16-2203 · Cited by 111 · see citing works
Excitotoxic neuroprotection and vulnerability with CaMKII inhibition
Ashpole, N. M., & Hudmon, A. (2011) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2011.02.003 · Cited by 100 · see citing works
Son, S. M., Song, H., Byun, J., Park, K. S., Jang, H. C., Park, Y. J., & Mook‐Jung, I. (2012) · Autophagy · doi:10.4161/auto.21861 · Cited by 98 · see citing works
Relationship Between Type 2 Diabetes Mellitus and Cognitive Change in a Multiethnic Elderly Cohort
Bangen, K. J., Gu, Y., Gross, A. L., Schneider, B. C., Skinner, J. C., Benitez, A. M., Sachs, B. C., Shih, R. A., Sisco, S. M., Schupf, N., et al. (2015) · Journal of the American Geriatrics Society · doi:10.1111/jgs.13441 · Cited by 91 · see citing works
Islet Amyloid Polypeptide (IAPP): A Second Amyloid in Alzheimer's Disease
Fawver, J. N., Ghiwot, Y., Koola, C., Carrera, W., Rodriguez-Rivera, J., Hernandez, C. M., Dineley, K. T., Kong, Y., Li, J., Jhamandas, J. H., et al. (2014) · Current Alzheimer Research · doi:10.2174/1567205011666141107124538 · Cited by 90 · see citing works
Brain Aging and AD-Like Pathology in Streptozotocin-Induced Diabetic Rats
Wang, J., Yin, J., Song, Y., Zhang, L., Ren, Y.-X., Wang, D., Gao, L., & Jing, Y. (2014) · Journal of Diabetes Research · doi:10.1155/2014/796840 · Cited by 89 · see citing works
Gutierrez, J., Rundek, T., Ekind, M. S. V., Sacco, R. L., & Wright, C. B. (2013) · American Journal of Neuroradiology · doi:10.3174/ajnr.a3498 · Cited by 86 · see citing works
Niedowicz, D. M., Reeves, V. L., Platt, T. L., Köhler, K., Beckett, T. L., Powell, D. K., Lee, T., Sexton, T. R., Song, E. S., Brewer, L. D., et al. (2014) · Acta Neuropathologica Communications · doi:10.1186/2051-5960-2-64 · Cited by 85 · see citing works
Amylin deposition in the kidney of patients with diabetic nephropathy
Gong, W., Liu, Z., Zeng, C., Peng, A., Chen, H. P., Zhou, H., & Li, L. S. (2007) · Kidney International · doi:10.1038/sj.ki.5002305 · Cited by 83 · see citing works
Diabetes is Not Associated with Alzheimer’s Disease Neuropathology
Matioli, M. N. P. D. S., Suemoto, C. K., Rodriguez, R. D., Farias, D. S., da Silva, M. M., Leite, R. E. P., Ferretti‐Rebustini, R. E. D. L., Farfel, J. M., Pasqualucci, C. A., Filho, W. J., et al. (2017) · Journal of Alzheimer s Disease · doi:10.3233/jad-170179 · Cited by 80 · see citing works
Brain microvascular injury and white matter disease provoked by diabetes‐associated hyperamylinemia
Ly, H., Verma, N., Wu, F., Liu, M., Saatman, K. E., Nelson, P. T., Slevin, J. T., Goldstein, L. B., Biessels, G. J., & Despa, F. (2017) · Annals of Neurology · doi:10.1002/ana.24992 · Cited by 79 · see citing works
Self-citationType 2 Diabetes, Skin Autofluorescence, and Brain Atrophy
Moran, C., Münch, G. W., Forbes, J. M., Beare, R. J., Blizzard, L., Venn, A., Phan, T. G., Chen, J., & Srikanth, V. K. (2014) · Diabetes · doi:10.2337/db14-0506 · Cited by 77 · see citing works
Initiative, A. D. N., Roostaei, T., Nazeri, A., Felsky, D., Jager, P. L. D., Schneider, J. A., Pollock, B. G., Bennett, D. A., & Voineskos, A. N. (2016) · Molecular Psychiatry · doi:10.1038/mp.2016.35 · Cited by 70 · see citing works
Caunca, M. R., Brutto, V. J. D., Gardener, H. E., Shah, N. H., Dequatre‐Ponchelle, N., Cheung, Y. K., Elkind, M. S. V., Brown, T. R., Cordonnier, C., Sacco, R. L., et al. (2016) · Journal of the American Heart Association · doi:10.1161/jaha.116.003477 · Cited by 70 · see citing works
Amylin alters human brain pericyte viability and NG2 expression
Schultz, N., Byman, E., Fex, M., & Wennström, M. (2016) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x16657093 · Cited by 69 · see citing works
Verma, N., Ly, H., Liu, M., Chen, J., Zhu, H., Chow, M., Hersh, L. B., & Despa, F. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-160047 · Cited by 67 · see citing works
Self-citationCommittee Report: Glycemic targets for elderly patients with diabetes
(2017) · Journal of Diabetes Investigation · doi:10.1111/jdi.12599 · Cited by 67 · see citing works
Diabetes, Hemoglobin A1C, and Regional Alzheimer Disease and Infarct Pathology
Pruzin, J. J., Schneider, J. A., Capuano, A. W., Leurgans, S. E., Barnes, L. L., Ahima, R. S., Arnold, S. E., Bennett, D. A., & Arvanitakis, Z. (2016) · Alzheimer Disease & Associated Disorders · doi:10.1097/wad.0000000000000172 · Cited by 63 · see citing works
American Diabetes Association (2016) · Diabetes Care · doi:10.2337/dc17-s014 · Cited by 62 · see citing works
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 61 · see citing works
Self-citationPrediabetes-induced vascular alterations exacerbate central pathology in APPswe/PS1dE9 mice
Ramos‐Rodríguez, J. J., Ortiz-Barajas, O., Gamero-Carrasco, C., de la Rosa, P. R., Infante‐Garcia, C., Zopeque-Garcia, N., Lechuga-Sancho, A. M., & Garcı́a-Alloza, M. (2014) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2014.06.005 · Cited by 60 · see citing works
Bouvy, W. H., Zwanenburg, J. J. M., Reinink, R., Wisse, L. E. M., Luijten, P. R., Kappelle, L. J., Geerlings, M. I., Biessels, G. J., & On behalf of the Utrecht Vascular Cognitive Impairment (VCI) Study group (2016) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x16648970 · Cited by 58 · see citing works
Self-citationMattson, M. P., & Rydel, R. E. (1996) · Nature · doi:10.1038/382674a0 · Cited by 57 · see citing works
Neuroimaging and its Relevance to Understanding Pathways Linking Diabetes and Cognitive Dysfunction
Moran, C., Beare, R. J., Phan, T. G., STARKSTEIN, S. E., Bruce, D. G., Mizrahi, R., & Srikanth, V. K. (2017) · Journal of Alzheimer s Disease · doi:10.3233/jad-161166 · Cited by 53 · see citing works
Heath, C. A., Mercer, S. W., & Guthrie, B. (2014) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2014-309033 · Cited by 52 · see citing works
Hippocampal calcium dysregulation at the nexus of diabetes and brain aging
Thibault, O., Anderson, K. L., DeMoll, C., Brewer, L. D., Landfield, P. W., & Porter, N. M. (2013) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2013.07.024 · Cited by 45 · see citing works
Bell, G. A., & Fadool, D. A. (2017) · Physiology & Behavior · doi:10.1016/j.physbeh.2017.02.044 · Cited by 34 · see citing works
Impaired amyloid β-degrading enzymes in brain of streptozotocin-induced diabetic rats
Liu, Y., Liu, L., Lü, S., Wang, D., Liu, X., Xie, L. Y., & Wang, G. (2011) · Journal of Endocrinological Investigation · doi:10.1007/bf03346691 · Cited by 33 · see citing works
Brady, C. C., Vannest, J. J., Dolan, L. M., Kadis, D. S., Lee, G. R., Holland, S. K., Khoury, J. C., & SHAH, A. S. (2016) · Pediatric Diabetes · doi:10.1111/pedi.12383 · Cited by 32 · see citing works
Diabetes mellitus and risk of early‐onset Alzheimer's disease: a population‐based case–control study
Kadohara, K., Sato, I., & Kawakami, K. (2017) · European Journal of Neurology · doi:10.1111/ene.13312 · Cited by 32 · see citing works
New animal models of Alzheimer’s disease that display insulin desensitization in the brain
Gao, C., Liu, Y., Li, L., & Hölscher, C. (2013) · Reviews in the Neurosciences · doi:10.1515/revneuro-2013-0034 · Cited by 31 · see citing works
Glycated haemoglobin (HbA1c), diabetes and trajectories of change in episodic memory performance
Pappas, C. A., Andel, R., Infurna, F. J., & Seetharaman, S. (2016) · Journal of Epidemiology & Community Health · doi:10.1136/jech-2016-207588 · Cited by 27 · see citing works
Ilaiwy, A., Liu, M., Parry, T. L., Bain, J. R., Newgard, C. B., Schisler, J. C., Muehlbauer, M. J., Despa, F., & Willis, M. S. (2016) · Metabolomics · doi:10.1007/s11306-016-1022-9 · Cited by 24 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Xue, M., Xu, W., Ou, Y.-N., Cao, X.-P., Tan, M.-S., Tan, L., & Yu, J.-T. (2019) · Ageing Research Reviews · doi:10.1016/j.arr.2019.100944 · Cited by 715 · see citing works
Type 2 diabetes and cognitive dysfunction–towards effective management of both comorbidities
Srikanth, V., Sinclair, A. J., Hill-Briggs, F., Moran, C., & Biessels, G. J. (2020) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(20)30118-2 · Cited by 465 · see citing works
Self-citationElSayed, N. A., Aleppo, G., Aroda, V. R., Bannuru, R. R., Brown, F. M., Bruemmer, D., Collins, B. S., Hilliard, M. E., Isaacs, D., Johnson, E. L., et al. (2023) · Diabetes Care · doi:10.2337/dc23-s005 · Cited by 362 · see citing works
Michailidis, M., Moraitou, D., Tata, D. A., Kalinderi, K., Papamitsou, T., & Papaliagkas, V. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23052687 · Cited by 330 · see citing works
Liss, J. L., Seleri Assunção, S., Cummings, J., Atri, A., Geldmacher, D. S., Candela, S. F., Devanand, D. P., Fillit, H. M., Susman, J., Mintzer, J., et al. (2021) · Journal of Internal Medicine · doi:10.1111/joim.13244 · Cited by 312 · see citing works
American Diabetes Association Professional Practice Committee (2022) · Diabetes Care · doi:10.2337/dc22-s005 · Cited by 445 · see citing works
American Diabetes Association Professional Practice Committee, ElSayed, N. A., McCoy, R. G., Aleppo, G., Balapattabi, K., Beverly, E. A., Briggs Early, K., Bruemmer, D., Echouffo-Tcheugui, J. B., Eichorst, B., et al. (2025) · Diabetes Care · doi:10.2337/dc25-s005 · Cited by 305 · see citing works
Blood–Brain Barrier Breakdown in Alzheimer’s Disease: Mechanisms and Targeted Strategies
Alkhalifa, A. E., Al-Ghraiybah, N. F., Odum, J., Shunnarah, J. G., Austin, N., & Kaddoumi, A. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242216288 · Cited by 212 · see citing works
Blood-to-brain communication in aging and rejuvenation
Bieri, G., Schroer, A. B., & Villeda, S. A. (2023) · Nature Neuroscience · doi:10.1038/s41593-022-01238-8 · Cited by 156 · see citing works
Li, Y., Peng, Y., Shen, Y., Zhang, Y., Liu, L., & Yang, X. (2023) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2022.2076064 · Cited by 156 · see citing works
The mechanism and efficacy of GLP-1 receptor agonists in the treatment of Alzheimer’s disease
Du, H., Meng, X., Yao, Y., & Xu, J. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.1033479 · Cited by 125 · see citing works
Cheng, D., Yang, S., Zhao, X., & Wang, G. (2022) · Drug Design, Development and Therapy · doi:10.2147/dddt.s348055 · Cited by 84 · see citing works
Tian, S., Jiang, J., Wang, J., Zhang, Z., Miao, Y., Ji, X., & Bi, Y. (2023) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.3673 · Cited by 79 · see citing works
Li, Q., Jia, M., Yan, Z., Li, Q., Sun, F., He, C., Li, Y., Zhou, X., Zhang, H., Liu, X., et al. (2021) · Journal of the American Heart Association · doi:10.1161/jaha.120.020734 · Cited by 77 · see citing works
Chiba, Y., Sugiyama, Y., Nishi, N., Nonaka, W., Murakami, R., & Ueno, M. (2020) · Neuropathology · doi:10.1111/neup.12665 · Cited by 59 · see citing works
Automated insulin delivery in older adults with type 1 diabetes
Kudva, Y. C., Henderson, R. J., Kanapka, L. G., Weinstock, R. S., Rickels, M. R., Pratley, R. E., Chaytor, N., Janess, K., Desjardins, D., Pattan, V., et al. (2025) · NEJM Evidence · doi:10.1056/evidoa2400200 · Cited by 45 · see citing works
Ross, A. B., Shertukde, S. P., Livingston Staffier, K., Chung, M., Jacques, P. F., & McKeown, N. M. (2023) · Advances in Nutrition · doi:10.1016/j.advnut.2023.04.003 · Cited by 41 · see citing works
Onset age of diabetes and incident dementia: A prospective cohort study
Wang, Y., Li, C., Liang, J., Gao, D., Pan, Y., Zhang, W., Zhang, Y., Zheng, F., & Xie, W. (2023) · Journal of Affective Disorders · doi:10.1016/j.jad.2023.02.138 · Cited by 36 · see citing works
Ding, Z., Leung, P.-Y., Lee, T.-L., & Chan, A. S. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2023.101886 · Cited by 31 · see citing works
[Retracted] A Review of Bile Acid Metabolism and Signaling in Cognitive Dysfunction‐Related Diseases
Weng, Z.-B., Chen, Y.-R., Lv, J.-T., Wang, M.-X., Chen, Z.-Y., Zhou, W., Shen, X.-C., Zhan, L.-B., & Wang, F. (2022) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2022/4289383 · Cited by 32 · see citing works
“According to the DCD development process or severity, it can be divided into asymptomatic preclinical MCI stage and dementia stage [133].”
RetractedLuan, S., Cheng, W., Wang, C., Gong, J., & Zhou, J. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.1047883 · Cited by 25 · see citing works
Pai, Y., Chen, I., Lin, J., Chen, X., Chen, H., Chang, M., Huang, J., & Lin, C. (2024) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.15918 · Cited by 26 · see citing works
How to manage comorbidities in people with dementia: A scoping review
Ma, D., Wang, Y., Zhao, Y., Meng, X., Su, J., Zhi, S., Song, D., Gao, S., Sun, J., & Sun, J. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2023.101937 · Cited by 25 · see citing works
Association of shift work with incident dementia: a community-based cohort study
Liao, H., Pan, D., Deng, Z., Jiang, J., Cai, J., Liu, Y., He, B., Lei, M., Li, H., Li, Y., et al. (2022) · BMC Medicine · doi:10.1186/s12916-022-02667-9 · Cited by 24 · see citing works
Dopamine-mediated autocrine inhibition of insulin secretion
Ferrero, E., Masini, M., Carli, M., Moscato, S., Beffy, P., Vaglini, F., Mattii, L., Corti, A., Scarselli, M., Novelli, M., et al. (2024) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2024.112294 · Cited by 4 · see citing works
“Recently, convincing evidence has been provided supporting a connection between brain damage and type 2 diabetes (Hamed, 2017; Biessels and Despa, 2018).”
- Authors
- Biessels, G. J., & Despa, F.
- Affiliations
- University Medical Center Utrecht (NL)
- University of Kentucky (US)
- Corresponding author
- Biessels, Geert Jan
- Venue
- Nature Reviews Endocrinology
- Published
- 2018-07-18
- Volume
- 14
- Issue
- 10
- Pages
- 591-604
- ISSN
- 1759-5029 (ISSN-L)
- 1759-5037
- PMC
- PMC6397437
- OpenAlex
- W2884234047
- Cited by
- 1,454
- References
- 124
- Citations by year
- 2026: 240 · 2025: 257 · 2024: 261 · 2023: 201 · 2022: 196 · 2021: 140 · 2020: 107 · 2019: 46 · 2018: 5
- FWCI
- 11.51
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Nature Reviews Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- Funders
- National Institutes of Health
- National Institute on Aging (P30AG028383, R01AG057290, R01AG053999)
- National Heart, Lung, and Blood Institute (R01HL118474)
- National Institute of Neurological Disorders and Stroke (R01NS116058)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- diabetes mellitus, cognitive decline, dementia, mild cognitive impairment, Alzheimer's disease, vascular dementia, neurofibrillary tangles, neuritic plaques, neuroimaging, neuropathology, risk factors, experimental model, translational research, prevention and treatment
- MeSH terms
- Aged, Alzheimer Disease, Dementia, Diabetes Mellitus, Type 2, Female, Humans, Male, Middle Aged, Prognosis, Severity of Illness Index, Comorbidity, Prevalence, Age Distribution, Sex Distribution, Risk Assessment, Neuroimaging, Cognitive Dysfunction
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
