Working Memory Impairment in Type 2 Diabetes: A Neurocognitive and Pathophysiological Review
Subject Areas : psychologyAmir Reza Majidi 1 , Soghra Ebrahimi Ghavam 2 , Ehsan Rezayat 3 *
1 - Allameh Tabataba’i University
2 - Allameh Tabataba’i University
3 - Department of Cognitive Sciences, Faculty of Psychology and Education, University of Tehran, Tehran, Iran.
Keywords: Type 2 Diabetes Mellitus (T2DM), Working Memory, Insulin Resistance, Neuroinflammation, Cognition,
Abstract :
Abstract: Type 2 diabetes mellitus (T2DM) extends beyond a simple metabolic disorder and is associated with a range of neural and cognitive alterations that can impact executive functions, including working memory. This review aims to comprehensively elucidate the pathophysiological mechanisms and evaluate behavioral and neuroimaging evidence related to working memory impairment in patients with T2DM. By analyzing studies published over the past two decades, data from cognitive tests (e.g., n-back, Stroop) and neuro imaging techniques (e.g., fMRI, MEG) were reviewed. Behavioral evidence indicates that diabetic patients exhibit poorer performance in working memory tasks compared to healthy individuals, with this decline linked to factors such as age, disease duration, and glycated hemoglobin (HbA1c) levels. From a neuro biological perspective, central insulin resistance, neuro inflammation, oxidative stress, reduced cerebro-vascular reactivity, and neurotransmitter dysfunction are identified as key contributors to these impairments. fMRI and MEG data further support disruptions in activity and connectivity within working memory networks, particularly in the anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (DLPFC), and hippocampus. Understanding the neural mechanisms underlying working memory decline in T2DM may facilitate early identification of at-risk patients and inform targeted clinical interventions to prevent cognitive deterioration.
خانلرزاده، فائزه؛ عسگری، کریم؛ و امینی، مسعود (1394). بررسی کارکردهای عصب‌روان‌شناختی در بیماران مبتلا به دیابت نوع دو. مجله دانشکده پزشکی دانشگاه علوم پزشکی مشهد، (8)58، 459-465.
شفیعی کندجانی، علیرضا؛، هوشیارقراملکی، جلیل؛ غفاری، نگین؛ و برزگردوغانی، حبیبه (1401). مقایسه حافظه و عملکرد اجرایی بیماران مبتلا به دیابت نوع دو با افراد عادی. مجله پزشکی دانشگاه علوم پزشکی تبریز، (1)44. 14-7.
نظری بدیع، مرضیه؛ عسگری، کریم؛ امینی، مسعود؛ و عابدی، احمد (1390). بررسی عملکردهای شناختی بیماران دیابتی نوع دو در مقایسه با بیماران پیش دیابتی. تازه‌های علوم شناختی، (3)13. 33-40.
Backeström, A., Papadopoulos, K., Eriksson, S., Olsson, T., Andersson, M., Blennow, K., Zetterberg, H., Nyberg, L., & Rolandsson, O. (2021). Acute hyperglycaemia leads to altered frontal lobe brain activity and reduced working memory in type 2 diabetes. PLoS One, 16(3), e0247753.
Bhagoji, S. B., Mirje, M., Patil, M., & Biradar, M. (2014). Working & short term memory status in type 2 diabetes mellitus. International Journal of Recent Trends in Science And Technology, 4(1). 85-88.
Braganza, D. C., Flores, E., Crew, L. A., Wirt, R. A., Ortiz, A. A., McNeela, A. M., Kinney, J. W., & Hyman, J. M. (2021). Diabetes mellitus affects working memory. Spectra Undergraduate Research Journal, 1(2), 3.
Chen, Y., Liu, Z., Zhang, J., Xu, K., Zhang, S., Wei, D., & Zhang, Z. (2014). Altered brain activation patterns under different working memory loads in patients with type 2 diabetes. Diabetes Care, 37(12), 3157-3163.
Dervan, R. (2014). Effect of duration of type 2 diabetes on short term and working memory. Medicine, International Journal of Medical and Pharmaceutical Sciences, 5(11), 24-27.
Embury, C. M., Lord, G. H., Drincic, A. T., Desouza, C. V., & Wilson, T. W. (2023). Glycemic control level alters working memory neural dynamics in adults with type 2 diabetes. Cerebral Cortex, 33(13), 8333-8341.
He, X. S., Wang, Z. X., Zhu, Y. Z., Wang, N., Hu, X., Zhang, D. R., Zhu, D. F., & Zhou, J. N. (2015). Hyperactivation of working memory-related brain circuits in newly diagnosed middle-aged type 2 diabetics. Acta Diabetol, 52(1), 133-142.
Huang, R.-R., Jia, B.-H., Xie, L., Ma, S.-H., Yin, J.-J., Sun, Z.-B., Le, H.-B., Xu, W.-C., Huang, J.-Z., & Luo, D.-X. (2016). Spatial working memory impairment in primary onset middle‐age type 2 diabetes mellitus: An ethology and BOLD‐fMRI study. Journal Magn Reson Imaging, 43(1), 75-87.
Ivnik, R. J., Malec, J. F., Tangalos, E. G., Petersen, R. C., Kokmen, E., & Kurland, L. T. (1990). The Auditory-Verbal Learning Test (AVLT): norms for ages 55 years and older. A Journal of Consulting and Clinical Psychology, 2(3), 304-312.
Kane, M. J., Conway, A. R. A., Miura, T. K., & Colflesh, G. J. H. (2007). Working memory, attention control, and the N-back task: a question of construct validity. Journal Expection Psychological Learn Memory Cognition, 33(3), 615-622.
Long, D. L., & Prat, C. S. (2002). Working memory and Stroop interference: An individual differences investigation. Memory Cognition, 30, 294-301.
Meneses, A. (2015). Serotonin, neural markers, and memory. Front Pharmacol, 6, 143.
Mythri, G., Babu, G. M., & Manjunath, M. L. (2017). Impact of type 2 diabetes mellitus on short term and working memory. Natlnal Journal Physiology Pharm Pharmacol, 7(10), 1095.
Oliel, Y., Ravona-Springer, R., Harel, M., Azuri, J., Botvin Moshe, C., Tanne, D., Haratz, S., Bendlin, B. B., Schnaider Beeri, M., & Livny, A. (2025). The role of cerebrovascular reactivity on brain activation during a working memory task in type 2 diabetes. Alzheimer's Dement Diagnosis Assession Disorder Monit, 17(1), e70045.
Ryan, C. M., Freed, M. I., Rood, J. A., Cobitz, A. R., Waterhouse, B. R., & Strachan, M. W. (2006). Improving metabolic control leads to better working memory in adults with type 2 diabetes. Diabetes Care, 29(2), 345-351.
Sadanand, S., Balachandar, R., & Bharath, S. (2016). Memory and executive functions in persons with type 2 diabetes: a meta‐analysis. Diabetes Metab Research Reveiw, 32(2), 132-142.
Sánchez-Cubillo, I., Periáñez, J. A., Adrover-Roig, D., Rodríguez-Sánchez, J. M., Ríos-Lago, M., Tirapu, J. E. E. A., & Barceló, F. (2009). Construct validity of the Trail Making Test: role of task-switching, working memory, inhibition/interference control, and visuomotor abilities. Journal International Neuropsychology Society, 15(3), 438-450.
Sola, T., Sola, F.-M., & Jehkonen, M. (2024). The effects of type 2 diabetes on cognitive performance: a review of reviews. International Journal Behavior Medicine, 1-15.
Talarowska, M., Florkowski, A., Zboralski, K., Orzechowska, A., & Gałecki, P. (2011). Visual and spatial working memory in a group of patients with type 1 and 2 diabetes. Diabet Dośw Klin, 11, 24-28.
Zhang, Y., Lu, S., Liu, C., Zhang, H., Zhou, X., Ni, C., Qin, W., & Zhang, Q. (2016). Altered brain activation and functional connectivity in working memory related networks in patients with type 2 diabetes: an ICA-based analysis. Scientific Reports, 6(1), 23767.