INVESTIGATION OF VOLUMETRIC ALTERATIONS IN THALAMIC SUBNUCLEI IN PROGRESSIVE AND STABLE MILD COGNITIVE IMPAIRMENT USING MAGNETIC RESONANCE IMAGING

Abstract

Objective: This study aimed to evaluate the volumes of thalamic subnuclei known to function in large-scale cognitive networks between progressive mild cognitive impairment (pMCI) and stable MCI (sMCI) groups progressing to dementia.

Materials and Methods: Magnetic resonance imaging and clinical data of 31 pMCI (Age: 68.66±6.86; education: 15.71±2.46; gender: 15 female) and 31 sMCI (Age: 70.18±7.24; education: 16.23±2.68; gender: 13 female) patients with no statistically significant differences in age, gender, education, and follow-up interval (mean 21 months) from the Alzheimer's Disease Neuroimaging Initiative database were used. FreeSurfer software was used for individual thalamus segmentation and volume calculation. Thalamic nuclei were divided into anterior, medial, posterior, lateral, ventral, and intralaminar nucleus groups. The volumes of each nucleus were normalised using intracranial volume. Normalised volumes were compared between groups using independent samples t-test, and false discovery rate (FDR) correction was applied. Correlation analysis was performed using florbetapir (AV45) PET scores to evaluate the relationship between amyloid burden in the brain and volumetric decrease.

Results: Statistically significant volumetric decreases were detected in the bilateral anterior (Right: t=2.432 p_FDR=0.048; Left: t=2.327 p_FDR=0.048) and lateral (t=2.372 p_FDR=0.048) nucleus groups in pMCI compared to sMCI. A negative correlation was found between PET scores and bilateral anterior nucleus groups (Right: r=-0.353 p=0.026, left: r=-0.350 p=0.026).

Conclusion: In our study, the anterior thalamic nucleus group, closely associated with memory, showed reduced volume in MCI patients who progressed to dementia, and this reduction correlated with amyloid burden in the brain. Based on the findings of our study, the anterior thalamic nucleus group may provide supportive value to other MRI biomarkers in predicting conversion to dementia.

Keywords

• Thalamus
• mild cognitive impairment
• magnetic resonance imaging
• dementia
• volumetric analysis

Project Number

TSA-2022-39128

References

1. Albert MS, DeKosky ST, Dickson D, Dubois B, Feldman HH, Fox NC, et al. The diagnosis of mild cognitive impairment due to Alzheimer’s disease: recommendations from the National Institute on Aging‐Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 2011;7(3):270-9. google scholar
2. Han JW, Kim TH, Lee SB, Park JH, Lee JJ, Huh Y, et al. Predictive validity and diagnostic stability of mild cognitive impairment subtypes. Alzheimers Dement 2012;8(6):553-9. google scholar
3. Aggleton JP, Vann SD, O’Mara SM. Converging diencephalic and hippocampal supports for episodic memory. Neuropsychologia 2023;191:108728. google scholar
4. Mitchell AS, Sherman SM, Sommer MA, Mair RG, Vertes RP, Chudasama Y. Advances in understanding mechanisms of thalamic relays in cognition and behavior. J Neurosci 2014;34(46):15340-6. google scholar
5. Sherman SM. The thalamus is more than just a relay. Curr Opin Neurobiol 2007;17(4):417-22. google scholar
6. Zarei M, Patenaude B, Damoiseaux J, Morgese C, Smith S, Matthews PM, et al. Combining shape and connectivity analysis: an MRI study of thalamic degeneration in Alzheimer’s disease. Neuroimage 2010;49(1):1-8. google scholar
7. Low A, Mak E, Malpetti M, Chouliaras L, Nicastro N, Su L, et al. Asymmetrical atrophy of thalamic subnuclei in Alzheimer’s disease and amyloid-positive mild cognitive impairment is associated with key clinical features. Alzheimers Dement 2019;11:690-9. google scholar
8. Hari E, Ulasoglu-Yildiz C, Kurt E, Bayram A, Gurvit H, Demiralp T. Volumetric and functional connectivity changes of the thalamic nuclei in different stages of Alzheimer’s disease. Clin Neurophysiol 2024;165:127-37. google scholar

9. Bernstein AS, Rapcsak SZ, Hornberger M, Saranathan M, Initiative ADN. Structural changes in thalamic nuclei across prodromal and clinical Alzheimer’s disease. J Alzheimers Dis 2021;82(1):361-71. google scholar
10. Fischl B, Salat DH, Busa E, Albert M, Dieterich M, Haselgrove C, et al. Whole brain segmentation: automated labeling of neuroanatomical structures in the human brain. Neuron 2002;33(3):341-55. google scholar
11. Dale AM, Fischl B, Sereno MI. Cortical surface-based analysis. I. Segmentation and surface reconstruction. Neuroimage 1999;9(2):179-94. google scholar
12. Iglesias JE, Insausti R, Lerma-Usabiaga G, Bocchetta M, Van Leemput K, Greve DN, et al. A probabilistic atlas of the human thalamic nuclei combining ex vivo MRI and histology. Neuroimage 2018;183:314-26. google scholar
13. Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Series B Stat Methodol 1995;57(1):289-300. google scholar
14. Zidan M, Boban J, Bjelan M, Todorović A, Vujanić TS, Semnic M, et al. Thalamic volume loss as an early sign of amnestic mild cognitive impairment. J Clinical Neurosci 2019;68:168-73. google scholar
15. de Jong LW, van der Hiele K, Veer IM, Houwing JJ, Westendorp RGJ, Bollen E, et al. Strongly reduced volumes of putamen and thalamus in Alzheimer’s disease: an MRI study. Brain 2008;131(12):3277-85. google scholar
16. Banerjee A, Yang F, Dutta J, Cacciola A, Hornberger M, Saranathan M. Atrophy patterns of deep gray matter nuclei in Alzheimer’s disease and frontotemporal dementia. J Alzheimers Dis 2025;108(4):1760-77 . google scholar
17. Morel A, Magnin M, Jeanmonod D. Multiarchitectonic and stereotactic atlas of the human thalamus. J Comp Neurol 1997;387(4):588-630. google scholar
18. Papez JW. A proposed mechanism of emotion. Arch NeurPsych 1937;38(4):725-43. google scholar
19. Aggleton JP, Brown MW. Episodic memory, amnesia, and the hippocampal–anterior thalamic axis. Behav Brain Sci 1999;22(3):425-44. google scholar
20. Aggleton JP, Pralus A, Nelson AJD, Hornberger M. Thalamic pathology and memory loss in early Alzheimer’s disease: moving the focus from the medial temporal lobe to Papez circuit. Brain 2016;139(7):1877-90. google scholar
21. Aggleton JP, O’Mara SM, Vann SD, Wright NF, Tsanov M, Erichsen JT. Hippocampal–anterior thalamic pathways for memory: uncovering a network of direct and indirect actions. Eur J Neurosci 2010;31(12):2292-307. google scholar
22. Jankowski MM, Ronnqvist KC, Tsanov M, Vann SD, Wright NF, Erichsen JT, et al. The anterior thalamus provides a subcortical circuit supporting memory and spatial navigation. Front Syst Neurosci 2013;7:45. google scholar
23. Swartz RH, Black SE. Anterior-medial thalamic lesions in dementia: frequent, and volume dependently associated with sudden cognitive decline. J Neurol Neurosurg Psychiatry 2006;77(12):1307-12. google scholar
24. Harding A, Halliday G, Caine D, Kril J. Degeneration of anterior thalamic nuclei differentiates alcoholics with amnesia. Brain 2000;123(1):141-54. google scholar
25. Cipolotti L, Husain M, Crinion J, Bird CM, Khan SS, Losseff N, et al. The role of the thalamus in amnesia: A tractography, high-resolution MRI and neuropsychological study. Neuropsychologia 2008;46(11):2745-58. google scholar
26. Braak H, Braak E. Alzheimer’s disease affects limbic nuclei of the thalamus. Acta Neuropathol 1991;81(3):261-8. google scholar