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Research progress on olfactory behavioral tests and MRI in the early diagnosis and intervention of cognitive decline in type 2 diabetes mellitus
WANG Shuang  LI Xin  ZHANG Wen  LU Jiaming  ZHANG Xin  ZHANG Bing 

Cite this article as: WANG S, LI X, ZHANG W, et al. Research progress on olfactory behavioral tests and MRI in the early diagnosis and intervention of cognitive decline in type 2 diabetes mellitus[J]. Chin J Magn Reson Imaging, 2026, 17(4): 109-113. DOI:10.12015/issn.1674-8034.2026.04.015.


[Abstract] Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease characterized by hyperglycemia and is associated with a significantly increased risk of cognitive decline and dementia. Early identification and intervention are crucial for delaying T2DM-related cognitive impairment. Studies have shown that patients with T2DM often exhibit abnormalities in olfactory perception and central olfactory processing, and olfactory dysfunction may serve as an early indicator of cognitive decline. This review summarizes the application of olfactory behavioral tests and magnetic resonance imaging in the early diagnosis and intervention of cognitive impairment in T2DM, with a particular focus on structural and functional alterations in olfactory-related brain regions revealed by magnetic resonance imaging studies. In addition, the current limitations of existing research and future research directions are discussed, aiming to provide references for the early identification and intervention of T2DM-related cognitive impairment.
[Keywords] type 2 diabetes；olfactory disorders；cognitive decline；magnetic resonance imaging；structural magnetic resonance imaging；functional magnetic resonance imaging

WANG Shuang1   LI Xin1, 2   ZHANG Wen1, 2   LU Jiaming1, 2   ZHANG Xin1, 2*   ZHANG Bing1, 2  

1 Department of Radiology, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing 210008, China

2 Department of Radiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing 210008, China

Corresponding author: ZHANG X, E-mail: neuro_zx@163.com

Conflicts of interest   None.

Received  2025-12-15
Accepted  2026-03-16
DOI: 10.12015/issn.1674-8034.2026.04.015
Cite this article as: WANG S, LI X, ZHANG W, et al. Research progress on olfactory behavioral tests and MRI in the early diagnosis and intervention of cognitive decline in type 2 diabetes mellitus[J]. Chin J Magn Reson Imaging, 2026, 17(4): 109-113. DOI:10.12015/issn.1674-8034.2026.04.015.

[1]
XUE M, XU W, OU Y N, et al. Diabetes mellitus and risks of cognitive impairment and dementia: a systematic review and meta-analysis of 144 prospective studies[J/OL]. Ageing Res Rev, 2019, 55: 100944 [2025-12-15]. https://doi.org/10.1016/j.arr.2019.100944. DOI: 10.1016/j.arr.2019.100944.
[2]
LIU L M, CHEN J Y, XIONG J. Recent advance in role of cerebral microvascular lesions in type 2 diabetes mellitus-associated cognitive impairment[J]. Chinese Journal of Neuromedicine, 2024, 23(1): 83-88. DOI: 10.3760/cma.j.cn115354-20230803-00043.
[3]
DANG L J, ZHAO Y, GAO L, et al. Relationship between type 2 diabetes mellitus and cognitive decline: a 4-year prospective cohort study[J]. Journal of Xi'an Jiaotong University (Medical Sciences), 2025, 46(5): 749-754. DOI: 10.7652/jdyxb202505005.
[4]
DING X H, YIN L, ZHANG L, et al. Diabetes accelerates Alzheimer's disease progression in the first year post mild cognitive impairment diagnosis[J]. Alzheimers Dement, 2024, 20(7): 4583-4593. DOI: 10.1002/alz.13882.
[5]
BHATIA-DEY N, HEINBOCKEL T. The olfactory system as marker of neurodegeneration in aging, neurological and neuropsychiatric disorders[J/OL]. Int J Environ Res Public Health, 2021, 18(13): 6976 [2025-12-15]. https://doi.org/10.3390/ijerph18136976. DOI: 10.3390/ijerph18136976.
[6]
DING Q, ZHANG Z, YU C C, et al. Relationship between olfaction and cognitive function in patients with type 2 diabetes mellitus: a follow-up study[J]. Chinese Journal of Diabetes, 2022, 14(12): 1404-1409. DOI: 10.3760/cma.j.cn115791-20220508-00204.
[7]
CARDELLA A, FERRULLI A, VUJOSEVIC S, et al. Olfactory dysfunction in patients with type 2 diabetes mellitus[J]. Rhinology, 2024, 62(5): 537-547. DOI: 10.4193/Rhin23.451.
[8]
GOUVERI E, KATOTOMICHELAKIS M, GOUVERIS H, et al. Olfactory dysfunction in type 2 diabetes mellitus: an additional manifestation of microvascular disease?[J]. Angiology, 2014, 65(10): 869-876. DOI: 10.1177/0003319714520956.
[9]
MA Y X, LI M, CHEN M, et al. Efficacy observation of hyperbaric oxygen comprehensive therapy for olfactory dysfunction in type 2 diabetes neuropathy[J]. Chinese Journal of Nautical Medicine and Hyperbaric Medicine, 2021, 28(6): 802-804. DOI: 10.3760/cma.j.cn311847-20210722-00215.
[10]
RAMOS-CAZORLA P, CARAZO-BARRIOS L, REYES-BUENO J A, et al. Olfactory dysfunction as a biomarker for early diagnosis of cognitive impairment in patients with type 2 diabetes: a systematic review[J/OL]. J Diabetes Res, 2024, 2024: 9933957 [2025-12-15]. https://doi.org/10.1155/jdr/9933957. DOI: 10.1155/jdr/9933957.
[11]
THANARAJAH S E, HOFFSTALL V, RIGOUX L, et al. The role of insulin sensitivity and intranasally applied insulin on olfactory perception[J/OL]. Sci Rep, 2019, 9: 7222 [2025-12-15]. https://doi.org/10.1038/s41598-019-43693-7. DOI: 10.1038/s41598-019-43693-7.
[12]
POESSEL M, FREIHERR J, WIENCKE K, et al. Insulin resistance is associated with reduced food odor sensitivity across a wide range of body weights[J/OL]. Nutrients, 2020, 12(8): 2201 [2025-12-15]. https://doi.org/10.3390/nu12082201. DOI: 10.3390/nu12082201.
[13]
GOUVERI E, PAPANAS N. Olfactory dysfunction: a complication of diabetes or a factor that complicates glucose metabolism? A narrative review[J/OL]. J Clin Med, 2021, 10(23): 5637 [2025-12-15]. https://doi.org/10.3390/jcm10235637. DOI: 10.3390/jcm10235637.
[14]
FATUZZO I, NICCOLINI G F, ZOCCALI F, et al. Neurons, nose, and neurodegenerative diseases: olfactory function and cognitive impairment[J/OL]. Int J Mol Sci, 2023, 24(3): 2117 [2025-12-15]. https://doi.org/10.3390/ijms24032117. DOI: 10.3390/ijms24032117.
[15]
CATURANO A, ROCCO M, TAGLIAFERRI G, et al. Oxidative stress and cardiovascular complications in type 2 diabetes: From pathophysiology to lifestyle modifications[J/OL]. Antioxidants, 2025, 14(1): 72 [2025-12-15]. https://doi.org/10.3390/antiox14010072. DOI: 10.3390/antiox14010072.
[16]
GONG L N, XIE J F, LIU J, et al. Olfactory dysfunction is a risk factor for the comorbidity of mild cognitive impairment and type 2 diabetes mellitus[J]. Journal of Central South University (Medical Science), 2021, 46(8): 831-837. DOI: 10.11817/j.issn.1672-7347.2021.200046.
[17]
SANKE H, MITA T, YOSHII H, et al. Olfactory dysfunction predicts the development of dementia in older patients with type 2 diabetes[J/OL]. Diabetes Res Clin Pract, 2021, 174: 108740 [2025-12-15]. https://doi.org/10.1016/j.diabres.2021.108740. DOI: 10.1016/j.diabres.2021.108740.
[18]
SIPOS L, GALAMBOSI Z, BOZÓKI S, et al. Statistical overview of the Sniffin' Sticks olfactory test from the perspectives of anosmia and hyposmia[J/OL]. Sci Rep, 2025, 15(1): 8984 [2025-12-15]. https://doi.org/10.1038/s41598-025-93380-z. DOI: 10.1038/s41598-025-93380-z.
[19]
MIDORIKAWA M, SUZUKI H, SUZUKI Y, et al. Relationships between cognitive function and odor identification, balance capability, and muscle strength in middle-aged persons with and without type 2 diabetes[J/OL]. J Diabetes Res, 2021, 2021: 9961612 [2025-12-15]. https://doi.org/10.1155/2021/9961612. DOI: 10.1155/2021/9961612.
[20]
SHARETT R, MOEIN S T, KHAN R, et al. Long-term taste and smell outcomes after COVID-19[J/OL]. JAMA Network Open, 2024, 7(4): e247818 [2025-12-15]. https://doi.org/10.1001/jamanetworkopen.2024.7818. DOI: 10.1001/jamanetworkopen.2024.7818.
[21]
GUO F, YUAN Z, YAO F S, et al. Development of the Chinese smell identification test[J]. Chem Senses, 2019, 44(3): 189-195. DOI: 10.1093/chemse/bjz006.
[22]
JOBIN B, MAGDAMO C, DELPHUS D, et al. The AROMHA brain health test is a remote olfactory assessment to screen for cognitive impairment[J/OL]. Sci Rep, 2025, 15: 92826 [2025-12-15]. https://doi.org/10.1038/s41598-025-92826-8. DOI: 10.1038/s41598-025-92826-8.
[23]
ZHOU F Y, ZHAO Z W, DAI J Y, et al. Olfactory testing with focus on odor identification for early detection of Alzheimer's disease in mild cognitive impairment[J/OL]. Am J Alzheimers Dis Other Demen, 2025, 40: 15333175251385615 [2025-12-15]. https://doi.org/10.1177/15333175251385615. DOI: 10.1177/15333175251385615.
[24]
TAE W S, HAM B J, PYUN S B, et al. Current clinical applications of structural magnetic resonance imaging in neurological disorders[J]. J Clin Neurol, 2025, 21(4): 277-293. DOI: 10.3988/jcn.2025.0185.
[25]
CHEN M, WANG J, ZHANG S L, et al. Brain structure as a correlate of odor identification and cognition in type 2 diabetes[J/OL]. Front Hum Neurosci, 2022, 16: 773309 [2025-12-15]. https://doi.org/10.3389/fnhum.2022.773309. DOI: 10.3389/fnhum.2022.773309.
[26]
MA T, LI Z Y, YU Y, et al. Gray and white matter abnormality in patients with T2DM-related cognitive dysfunction: a systemic review and meta-analysis[J/OL]. Nutr Diabetes, 2022, 12: 39 [2025-12-15]. https://doi.org/10.1038/s41387-022-00214-2. DOI: 10.1038/s41387-022-00214-2.
[27]
GURBÜZ D, KESIMLI M C, BILGILI A M, et al. Evaluation of olfactory bulb volume in patients with diabetic olfactopathy and comparison with healthy individuals[J]. B-ENT, 2021, 17(3): 174-178. DOI: 10.5152/B-ENT.2021.21311.
[28]
VURAL A, ALTUNIŞIK E, SUT S K, et al. Case–Controlled Clinical Assessment of the Olfactory System via Cranial Magnetic Resonance Imaging in Patients With Type 2 Diabetes Mellitus[J/OL]. Brain Behav, 2026, 16: e71210 [2025-12-15]. https://doi.org/10.1002/brb3.71210. DOI: 10.1002/brb3.71210.
[29]
ZHU Y J, LU J M, ZHANG X, et al. Advancements in olfactory related magnetic resonance imaging in patients with Alzheimer's disease[J]. Chinese Journal of CT and MRI, 2024, 22(1): 170-172. DOI: 10.3969/j.issn.1672-5131.2024.01.053.
[30]
ZHANG J H, XU H Z, SHEN Q F, et al. Nε-(carboxymethyl)-lysine, white matter, and cognitive function in diabetes patients[J]. Can J Neurol Sci, 2016, 43(4): 518-522. DOI: 10.1017/cjn.2015.398.
[31]
VAN BUSSEL F C G, BACKES W H, HOFMAN A M, et al. Altered hippocampal white matter connectivity in type 2 diabetes mellitus and memory decrements[J/OL]. J Neuroendocrinol, 2016, 28(3): 12366 [2025-12-15]. https://doi.org/10.1111/jne.12366. DOI: 10.1111/jne.12366.
[32]
ZHANG Y, CAO Y J, XIE Y J, et al. Altered brain structural topological properties in type 2 diabetes mellitus patients without complications[J]. J Diabetes, 2019, 11(2): 129-138. DOI: 10.1111/1753-0407.12826.
[33]
PLAILLY J, HOWARD J D, GITELMAN D R, et al. Attention to odor modulates thalamocortical connectivity in the human brain[J]. J Neurosci, 2008, 28(20): 5257-5267. DOI: 10.1523/JNEUROSCI.5015-07.2008.
[34]
TAN X, FANG P, AN J, et al. Micro-structural white matter abnormalities in type 2 diabetic patients: a DTI study using TBSS analysis[J]. Neuroradiology, 2016, 58(12): 1209-1216. DOI: 10.1007/s00234-016-1752-4.
[35]
SU Y, QI F, WANG M, et al. Changes of white matter microstructure in middle-aged patients with type 2 diabetes mellitus and no cognitive impairment[J]. Diagnostic Imaging & Interventional Radiology, 2020, 29(3): 177-182. DOI: 10.3969/j.issn.1005-8001.2020.03.004.
[36]
ZHOU C, LI J, DONG M, et al. Altered white matter microstructures in type 2 diabetes mellitus: a coordinate-based meta-analysis of diffusion tensor imaging studies[J/OL]. Front Endocrinol (Lausanne), 2021, 12: 658198 [2025-12-15]. https://doi.org/10.3389/fendo.2021.658198. DOI: 10.3389/fendo.2021.658198.
[37]
SHEN J, TENG Z, WU G Y, et al. Resting-state fMRI preliminary studies of type 2 diabetes mellitus patients with olfactory dysfunction[J]. Journal of Clinical Radiology, 2019, 38(3): 93-97. DOI: 10.13437/j.cnki.jcr.2019.03.004.
[38]
WU M, LI X, ZHANG W, et al. Investigation of the value of olfactory neural circuit remodeling in T2DM patients treated with three anti-diabetic drugs[J]. Chin J Magn Reson Imaging, 2025, 16(5): 456-462. DOI: 10.12015/issn.1674-8034.2025.05.008.
[39]
ZHANG Z, ZHANG B, WANG X, et al. Altered odor-induced brain activity as an early manifestation of cognitive decline in patients with type 2 diabetes[J]. Diabetes, 2018, 67(5): 994-1006. DOI: 10.2337/db17-1274.
[40]
NI W Y, ZHANG Z, ZHANG B, et al. Connecting peripheral to central neuropathy: examination of nerve conduction combined with olfactory tests in patients with type 2 diabetes[J]. Diabetes Metab Syndr Obes, 2021, 14: 3097-3107. DOI: 10.2147/DMSO.S312021.
[41]
ZHANG Z. The role of olfactory assessment and functional magnetic resonance imaging for early evaluation and intervention of cognitive decline in type 2 diabetes[D]. Nanjing: Nanjing University, 2019. DOI: 10.27235/d.cnki.gnjiu.2019.000247.
[42]
LI R S, HAN X L, HUA M Y, et al. Advances in magnetic resonance imaging studies in patients with cognitive impairment in type 2 diabetes mellitus[J]. Chin J Magn Reson Imaging, 2022, 13(2): 108-111, 115. DOI: 10.12015/issn.1674-8034.2022.02.026.
[43]
VAN DINTHER M, HOOGHIEMSTRA A M, BRON E E, et al. Lower cerebral blood flow predicts cognitive decline in patients with vascular cognitive impairment[J]. Alzheimers Dement, 2024, 20(1): 136-144. DOI: 10.1002/alz.13408.
[44]
YANG J Y, ZHANG X W, LIU X Q, et al. Altered Cerebral Blood Flow in Type 2 Diabetes Mellitus Without Cognitive Impairment[J]. Acta Academiae Medicinae Sinicae, 2025, 47(2): 219-225. DOI: 10.3881/j.issn.1000-503X.16155.
[45]
LUO W. Changes of cerebral blood flow and its functional connectivity in olfactory-related brain regions of type 2 diabetes mellitus[D]. Hefei: Anhui Medical University, 2022. DOI: 10.26921/d.cnki.ganyu.2022.000405.
[46]
ABDELHAY B, MUSTAPHA A, LAMIAE E, et al. Agonistes des récepteurs GLP-1 dans la maladie d'alzheimer: potentiel thérapeutique et mécanismes d'action[J]. Méd Malad Métab, 2024, 18(7): 609-617. DOI: 10.1016/j.mmm.2024.09.010.
[47]
ZANG Y R. Analysis of the effect of dapagliflozin on improving mild cognitive impairment in type 2 diabetes mellitus patients: a retrospective cohort study[D]. Jinan: Shandong University, 2024. DOI: 10.27272/d.cnki.gshdu.2024.003691.
[48]
CHENG H Y, ZHANG Z, ZHANG B, et al. Enhancement of impaired olfactory neural activation and cognitive capacity by liraglutide, but not dapagliflozin or acarbose, in patients with type 2 diabetes: a 16-week randomized parallel comparative study[J]. Diabetes Care, 2022, 45(5): 1201-1210. DOI: 10.2337/dc21-2064.
[49]
ZHANG Z, ZHANG B, WANG X, et al. Olfactory Dysfunction Mediates Adiposity in Cognitive Impairment of Type 2 Diabetes: Insights From Clinical and Functional Neuroimaging Studies[J]. Diabetes Care, 2019, 42(7): 1274-1283. DOI: 10.2337/dc18-2584.
[50]
LI X, ZHANG Y, BI Y, et al. Dapagliflozin restores odour-induced functional integration of primary olfactory cortex circuit but not olfactory-related regional brain activation in patients with type 2 diabetes: a 16-week randomised comparative study[J]. Diabetes Obes Metab, 2025, 27(12): 7309-7322. DOI: 10.1111/dom.70132.

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