Cognitive impairment, including Alzheimer's disease and other kinds of dementia, is a major health problem in older adults worldwide. Although numerous investigators have attempted to develop effective treatment modalities or drugs, there is no reasonably efficacious strategy for preventing or recovering from cognitive impairment. Therefore, modifiable risk factors for cognitive impairment have received attention, and the growing literature of metabolic risk factors for cognitive impairment has expanded from epidemiology to molecular pathogenesis and therapeutic management. This review focuses on the epidemiological evidence for the association between cognitive impairment and several endocrine risk factors, including insulin resistance, dyslipidemia, thyroid dysfunction, vitamin D deficiency, and subclinical atherosclerosis. Researches suggesting possible mechanisms for this association are reviewed. The research investigating modifiable endocrine risk factors for cognitive impairment provides clues for understanding the pathogenesis of cognitive impairment and developing novel treatment modalities. However, so far, interventional studies investigating the beneficial effect of the "modification" of these "modifiable risk factors" on cognitive impairment have reported variable results. Therefore, well-designed, randomized prospective interventional studies are needed.

Citations

Citations to this article as recorded by  

• Association between the neutrophil to lymphocyte ratio and mild cognitive impairment in patients with type 2 diabetes
  Zi-Wei Yu, Ying Wang, Xin Li, Xue-Wei Tong, Yi-Tong Zhang, Xin-Yuan Gao
  Aging Clinical and Experimental Research.2023; 35(6): 1339.     CrossRef
• Cognitive status and its risk factors in patients with hypertension and diabetes in a low‐income rural area of China: A cross‐sectional study
  Yuyan Guo, Ruifeng Liang, Jingjuan Ren, Liting Cheng, Mengqin Wang, Huilin Chai, Xiaoyu Cheng, Yaowen Yang, Yajuan Sun, Jiantao Li, Shuhong Zhao, Wenjing Hou, Jianhua Zhang, Feng Liu, Rong Wang, Qiao Niu, Hongmei Yu, Shoulin Yang, Jianying Bai, Hongmei Zh
  International Journal of Geriatric Psychiatry.2023;[Epub]     CrossRef
• Insulin Resistance and Glucose Metabolism during Infection
  Borros Arneth
  Endocrines.2023; 4(4): 685.     CrossRef
• Corresponding risk factors between cognitive impairment and type 1 diabetes mellitus: A narrative review
  Chen-Yang Jin, Shi-Wen Yu, Jun-Ting Yin, Xiao-Ying Yuan, Xu-Gang Wang
  Heliyon.2022; 8(8): e10073.     CrossRef
• Cerebrospinal fluid heart fatty acid‐binding protein as a predictive biomarker of neurodegeneration in Alzheimer’s disease
  Lu Pan, Ya-Nan Ou, Lin Tan, Lan Tan, Jin-Tai Yu
  Brain Science Advances.2021; 7(1): 44.     CrossRef
• Endocrine dysfunction and cognitive impairment
  Valeria CALSOLARO, Marina BOTTARI, Giulia COPPINI, Bianca LEMMI, Fabio MONZANI
  Minerva Endocrinology.2021;[Epub]     CrossRef
• Effect of hypothyroidism on cognitive status: Evidence from stroop task
  Shilpi Goyal, Abhinav Dixit, Neelam Vaney, SV Madhu
  Indian Journal of Medical Specialities.2020; 11(1): 34.     CrossRef
• Statin use and safety concerns: an overview of the past, present, and the future
  Rubina Mulchandani, Tanica Lyngdoh, Ashish Kumar Kakkar
  Expert Opinion on Drug Safety.2020; 19(8): 1011.     CrossRef
• Neurocognitive impairment in type 2 diabetes mellitus
  Marianna Karvani, P. Simos, S. Stavrakaki, D. Kapoukranidou
  Hormones.2019; 18(4): 523.     CrossRef
• TDP-43 proteinopathy in aging: Associations with risk-associated gene variants and with brain parenchymal thyroid hormone levels
  Peter T. Nelson, Zsombor Gal, Wang-Xia Wang, Dana M. Niedowicz, Sergey C. Artiushin, Samuel Wycoff, Angela Wei, Gregory A. Jicha, David W. Fardo
  Neurobiology of Disease.2019; 125: 67.     CrossRef
• Treated hypothyroidism is associated with cerebrovascular disease but not Alzheimer's disease pathology in older adults
  Willa D. Brenowitz, Fang Han, Walter A. Kukull, Peter T. Nelson
  Neurobiology of Aging.2018; 62: 64.     CrossRef
• Translating molecular advances in Down syndrome and Fragile X syndrome into therapies
  Victor Faundez, Ilario De Toma, Barbara Bardoni, Renata Bartesaghi, Dean Nizetic, Rafael de la Torre, Roi Cohen Kadosh, Yann Herault, Mara Dierssen, Marie-Claude Potier, Stylianos Antonarakis, Renata Bartesaghi, Andrea Contestabile, Tonnie Coppus, Peter D
  European Neuropsychopharmacology.2018; 28(6): 675.     CrossRef
• Associations between waist circumference, metabolic risk and executive function in adolescents: A cross-sectional mediation analysis
  Anna Bugge, Sören Möller, Daniel R. Westfall, Jakob Tarp, Anne K. Gejl, Niels Wedderkopp, Charles H. Hillman, Ying-Mei Feng
  PLOS ONE.2018; 13(6): e0199281.     CrossRef
• BsmI polymorphism in the vitamin D receptor gene is associated with 25-hydroxy vitamin D levels in individuals with cognitive decline
  Ana Carolina R. de Oliveira, Carolina A. Magalhães, Cristina M. G. Loures, Vanessa G. Fraga, Leonardo C. de Souza, Henrique C. Guimarães, Marco T. G. Cintra, Maria A. Bicalho, Maira C. R. Sousa, Josianne N. Silveira, Ieda F. O. Silva, Paulo Caramelli, Mar
  Arquivos de Neuro-Psiquiatria.2018; 76(11): 760.     CrossRef
• Traumatic brain injury: sex, gender and intersecting vulnerabilities
  Tatyana Mollayeva, Shirin Mollayeva, Angela Colantonio
  Nature Reviews Neurology.2018; 14(12): 711.     CrossRef
• Determinants of poor cognitive function using A-IQCODE among Lebanese older adults: a cross-sectional study
  Ibrahim R. Bou-Orm, Assem M. Khamis, Monique Chaaya
  Aging & Mental Health.2018; 22(6): 844.     CrossRef
• Articles inEndocrinology and Metabolismin 2016
  Won-Young Lee
  Endocrinology and Metabolism.2017; 32(1): 62.     CrossRef
• Alcohol consumption and gastric cancer risk: a meta-analysis of prospective cohort studies
  Xue Han, Li Xiao, Yao Yu, Yu Chen, Hai-Hua Shu
  Oncotarget.2017; 8(47): 83237.     CrossRef
• Functional capacity and obesity reflect the cognitive performance of older adults living in long‐term care facilities
  Karine Gonçalves Damascena, Cristiane Batisti Ferreira, Pâmela dos Santos Teixeira, Bibiano Madrid, Alexandre Gonçalves, Cláudio Córdova, Otávio de Toledo Nóbrega, Aparecido Pimentel Ferreira
  Psychogeriatrics.2017; 17(6): 439.     CrossRef
• Insulin resistance, dyslipidemia, and apolipoprotein E interactions as mechanisms in cognitive impairment and Alzheimer's disease
  Therese S Salameh, Elizabeth M Rhea, William A Banks, Angela J Hanson
  Experimental Biology and Medicine.2016; 241(15): 1676.     CrossRef
• Role of the Orexin System on the Hypothalamus-Pituitary-Thyroid Axis
  Antonietta Messina, Carolina De Fusco, Vincenzo Monda, Maria Esposito, Fiorenzo Moscatelli, Anna Valenzano, Marco Carotenuto, Emanuela Viggiano, Sergio Chieffi, Vincenzo De Luca, Giuseppe Cibelli, Marcellino Monda, Giovanni Messina
  Frontiers in Neural Circuits.2016;[Epub]     CrossRef
• Genomics and CSF analyses implicate thyroid hormone in hippocampal sclerosis of aging
  Peter T. Nelson, Yuriko Katsumata, Kwangsik Nho, Sergey C. Artiushin, Gregory A. Jicha, Wang-Xia Wang, Erin L. Abner, Andrew J. Saykin, Walter A. Kukull, David W. Fardo
  Acta Neuropathologica.2016; 132(6): 841.     CrossRef

As the prevalence and life expectancy of type 2 diabetes mellitus (T2DM) continue to increase, the importance of effective detection and intervention for the complications of T2DM, especially neurocognitive complications including cognitive dysfunction and dementia, is receiving greater attention. T2DM is thought to influence cognitive function through an as yet unclear mechanism that involves multiple factors such as hyperglycemia, hypoglycemia, and vascular disease. Recent developments in neuroimaging methods have led to the identification of potential neural correlates of T2DM-related neurocognitive changes, which extend from structural to functional and metabolite alterations in the brain. The evidence indicates various changes in the T2DM brain, including global and regional atrophy, white matter hyperintensity, altered functional connectivity, and changes in neurometabolite levels. Continued neuroimaging research is expected to further elucidate the underpinnings of cognitive decline in T2DM and allow better diagnosis and treatment of the condition.

Citations

Citations to this article as recorded by  

• The level of serum retinol-binding protein is associated with diabetic mild cognitive impairment
  Wenjie Zhang, Yuqi Yuan, Xiaoxia Cui, Shihong Chen, Xianghua Zhuang
  Brain Research.2024; 1822: 148670.     CrossRef
• Research Progress on Lipocalin-2 in Diabetic Encephalopathy
  Wenjie Zhang, Shihong Chen, Xianghua Zhuang
  Neuroscience.2023; 515: 74.     CrossRef
• Voluntary Attention and Quality of Life in Patients With Type 1 and Type 2 Diabetes Mellitus: Differences in Changes Depending on Disease Type and Duration
  N. E. Tadevosyan, A. S. Khachunts, M. Gohargani, A. A. Sahakyan, A. A. Tumanyan
  Journal of Evolutionary Biochemistry and Physiology.2022; 58(2): 569.     CrossRef
• Modifiable risk factors for neurocognitive and psychosocial problems after Hodgkin lymphoma
  AnnaLynn M. Williams, Sedigheh Mirzaei Salehabadi, Mengqi Xing, Nicholas S. Phillips, Matthew J. Ehrhardt, Rebecca Howell, Yutaka Yasui, Kevin C. Oeffinger, Todd Gibson, Eric J. Chow, Wendy Leisenring, Deokumar Srivastava, Melissa M. Hudson, Leslie L. Rob
  Blood.2022; 139(20): 3073.     CrossRef
• Type 2 Diabetes Independent of Glycemic Control is Associated With Cognitive Impairments: Findings From NHANES
  Rozmin Jiwani, Brittany Dennis, Alfonso L. Neri, Chandler Bess, Sara Espinoza, Jing Wang, Monica C. Serra
  Clinical Nursing Research.2022; 31(7): 1225.     CrossRef
• Diabetes and associated cognitive disorders: Role of the Hypothalamic-Pituitary Adrenal axis
  Nathalie Marissal-Arvy, Marie-Pierre Moisan
  Metabolism Open.2022; 15: 100202.     CrossRef
• Inside the diabetic brain: Insulin resistance and molecular mechanism associated with cognitive impairment and its possible therapeutic strategies
  Bhaskar Jyoti Dutta, Shamsher Singh, Sanket Seksaria, Ghanshyam Das Gupta, Amrita Singh
  Pharmacological Research.2022; 182: 106358.     CrossRef
• The role of LRP1 in Aβ efflux transport across the blood-brain barrier and cognitive dysfunction in diabetes mellitus
  Xue P, Long Zz, Jiang Gg, Wang Lp, Bian Cm, Wang Yl, M.F. Chen, Li W
  Neurochemistry International.2022; 160: 105417.     CrossRef
• Childhood Neurotoxicity and Brain Resilience to Adverse Events during Adulthood
  AnnaLynn M. Williams, Yin Ting Cheung, Geehong Hyun, Wei Liu, Kirsten K. Ness, Matthew J. Ehrhardt, Daniel A. Mulrooney, Nickhill Bhakta, Pia Banerjee, Tara M. Brinkman, Daniel M. Green, Wassim Chemaitilly, I‐Chan Huang, Deokumar Srivastava, Melissa M. Hu
  Annals of Neurology.2021; 89(3): 534.     CrossRef
• Metformin restores hippocampal neurogenesis and learning and memory via regulating gut microbiota in the obese mouse model
  Xiaoyi Ma, Wenchang Xiao, Hao Li, Pei Pang, Feixiao Xue, Lu Wan, Lei Pei, Huanhuan Yan
  Brain, Behavior, and Immunity.2021; 95: 68.     CrossRef
• Promoting Successful Cognitive Aging: A Ten-Year Update
  Taylor J. Krivanek, Seth A. Gale, Brittany M. McFeeley, Casey M. Nicastri, Kirk R. Daffner
  Journal of Alzheimer's Disease.2021; 81(3): 871.     CrossRef
• Association of Vitamin D Level and Nerve Conduction Study Parameters with Cognitive Function in Diabetic Neuropathy Patients
  Aida Fithrie, Fasihah Irfani Fitri, Muhammad Reza Putra
  Open Access Macedonian Journal of Medical Sciences.2021; 9(B): 72.     CrossRef
• Insulin resistance takes center stage: a new paradigm in the progression of bipolar disorder
  Cynthia V. Calkin
  Annals of Medicine.2019; 51(5-6): 281.     CrossRef
• Vitamin D Supplementation and Cognition in People with Type 2 Diabetes: A Randomized Control Trial
  Mary A. Byrn, William Adams, Sue Penckofer, Mary Ann Emanuele
  Journal of Diabetes Research.2019; 2019: 1.     CrossRef
• Neurocognitive impairment in type 2 diabetes mellitus
  Marianna Karvani, P. Simos, S. Stavrakaki, D. Kapoukranidou
  Hormones.2019; 18(4): 523.     CrossRef
• Benefits of combination low-dose pioglitazone plus fish oil on aged type 2 diabetes mice
  Yuzuru Iizuka, Hyounju Kim, Satoshi Hirako, Kanako Chiba, Masahiro Wada, Akiyo Matsumoto
  Journal of Food and Drug Analysis.2018; 26(4): 1265.     CrossRef
• Association of ApoE Genetic Polymorphism and Type 2 Diabetes with Cognition in Non-Demented Aging Chinese Adults: A Community Based Cross-Sectional Study
  Jie Zhen, Tong Lin, Xiaochen Huang, Huiqiang Zhang, Shengqi Dong, Yifan Wu, Linlin Song, Rong Xiao, Linhong Yuan
  Aging and disease.2018; 9(3): 346.     CrossRef
• Chronic Health Conditions and Neurocognitive Function in Aging Survivors of Childhood Cancer: A Report from the Childhood Cancer Survivor Study
  Yin Ting Cheung, Tara M Brinkman, Chenghong Li, Yasmin Mzayek, Deokumar Srivastava, Kirsten K Ness, Sunita K Patel, Rebecca M Howell, Kevin C Oeffinger, Leslie L Robison, Gregory T Armstrong, Kevin R Krull
  JNCI: Journal of the National Cancer Institute.2018; 110(4): 411.     CrossRef
• Diabetes, Depression, and Cognition: a Recursive Cycle of Cognitive Dysfunction and Glycemic Dysregulation
  Sheila Black, Kyle Kraemer, Avani Shah, Gaynell Simpson, Forrest Scogin, Annie Smith
  Current Diabetes Reports.2018;[Epub]     CrossRef
• Hypoglycemia is associated with dementia in elderly patients with type 2 diabetes mellitus: An analysis based on the Korea National Diabetes Program Cohort
  Sang Ouk Chin, Sang Youl Rhee, Suk Chon, Sei Hyun Baik, Yongsoo Park, Moon Suk Nam, Kwan Woo Lee, Ki Hong Chun, Jeong-taek Woo, Young Seol Kim
  Diabetes Research and Clinical Practice.2016; 122: 54.     CrossRef
• Bipolar disorders, type 2 diabetes mellitus, and the brain
  Tomas Hajek, Roger McIntyre, Martin Alda
  Current Opinion in Psychiatry.2016; 29(1): 1.     CrossRef
• 1,5-Anhydro-D-Glucitol Could Reflect Hypoglycemia Risk in Patients with Type 2 Diabetes Receiving Insulin Therapy
  Min Kyeong Kim, Hye Seung Jung, Soo Heon Kwak, Young Min Cho, Kyong Soo Park, Seong Yeon Kim
  Endocrinology and Metabolism.2016; 31(2): 284.     CrossRef
• Insulin in the nervous system and the mind: Functions in metabolism, memory, and mood
  Seung-Hwan Lee, Janice M. Zabolotny, Hu Huang, Hyon Lee, Young-Bum Kim
  Molecular Metabolism.2016; 5(8): 589.     CrossRef
• Toll-like receptor 2 and type 2 diabetes
  Zahra Sepehri, Zohre Kiani, Ali Akbar Nasiri, Farhad Kohan
  Cellular & Molecular Biology Letters.2016;[Epub]     CrossRef
• Long-term Variability in Glycemic Control Is Associated With White Matter Hyperintensities in APOE4 Genotype Carriers With Type 2 Diabetes
  Abigail Livny, Ramit Ravona-Springer, Anthony Heymann, Rachel Priess, Tammar Kushnir, Galia Tsarfaty, Leeron Rabinov, Reut Moran, Hadass Hoffman, Itzik Cooper, Lior Greenbaum, Jeremy Silverman, Mary Sano, Sterling C. Johnson, Barbara B. Bendlin, Michal Sc
  Diabetes Care.2016; 39(6): 1056.     CrossRef
• DIABETES MELLITUS Y SU ASOCIACIÓN CON DETERIORO COGNITIVO Y DEMENCIA
  Gonzalo Muñoz A., Christina Degen, Johannes Schröder, Pablo Toro E.
  Revista Médica Clínica Las Condes.2016; 27(2): 266.     CrossRef
• Blood electrolyte disturbances during severe hypoglycemia in Korean patients with type 2 diabetes
  Mi Yeon Kang
  The Korean Journal of Internal Medicine.2015; 30(5): 648.     CrossRef
• Whenever You Lose Connection, Take Intranasal Insulin?
  Antje Gottschalk, Björn Ellger
  Diabetes.2015; 64(3): 687.     CrossRef
• Spatial Patterns of Structural Brain Changes in Type 2 Diabetic Patients and Their Longitudinal Progression With Intensive Control of Blood Glucose
  Guray Erus, Harsha Battapady, Tianhao Zhang, James Lovato, Michael E. Miller, Jeff D. Williamson, Lenore J. Launer, R. Nick Bryan, Christos Davatzikos
  Diabetes Care.2015; 38(1): 97.     CrossRef
• Articles in 'Endocrinology and Metabolism' in 2014
  Won-Young Lee
  Endocrinology and Metabolism.2015; 30(1): 47.     CrossRef
• Cerebrolysin reverses hippocampal neural atrophy in a mice model of diabetes mellitus type 1
  Lizzette Sanchez‐Vega, Ismael Juárez, Maria De Jesus Gomez‐Villalobos, Gonzalo Flores
  Synapse.2015; 69(6): 326.     CrossRef