Poster No:
184
Submission Type:
Abstract Submission
Authors:
Atsushi Kimura1,2, Masahiro Hatakeyama3, Mikhail Ratanov1, Kosei Nakamura1, Hitoshi Shimada1
Institutions:
1Brain Research Institute, Niigata University, Niigata, Niigata, 2Clinial Research Institute of Clinical Pharmacology and Therapeutics, Showa University, Tokyo, Japan, 3Brain Research Institute, Niigata University, Niigata, Niigata
First Author:
Atsushi Kimura
Brain Research Institute, Niigata University|Clinial Research Institute of Clinical Pharmacology and Therapeutics, Showa University
Niigata, Niigata|Tokyo, Japan
Co-Author(s):
Mikhail Ratanov
Brain Research Institute, Niigata University
Niigata, Niigata
Kosei Nakamura
Brain Research Institute, Niigata University
Niigata, Niigata
Hitoshi Shimada
Brain Research Institute, Niigata University
Niigata, Niigata
Introduction:
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by impairments in memory and various cognitive functions, including language. Recent advances suggest that cerebellar circuits, which share extensive connections with the cerebral cortex, may also be targeted in AD. Functional MRI studies have reported disrupted functional connectivity in the cerebellum of AD patients (Zheng et al., 2017). Furthermore, pathological studies have revealed neurodegeneration and inflammation in the cerebellum comparable to that observed in the cerebral cortex (Alvarez et al., 2015).
We recently reported a case where aphasia, initially improved after parietal lobe infarction, recurred following a cerebellar hemorrhage, highlighting the role of the parietal lobe and cerebellum in language function (Kinoshita et al., 2024). Previous research has shown that Crus I and Crus II of the cerebellum are particularly involved in language processing (Nakatani et al., 2023). Clinically, there is growing evidence suggesting cerebellar involvement in language dysfunction in AD patients (Yang et al., 2024).
While these findings suggest cerebellar involvement in language function in AD, the detailed mechanisms remain unclear. Our study aims to elucidate the characteristics of cerebellar aphasia in AD by examining the relationship between structural changes in the cerebello-pontine tract and language function.
Methods:
We extracted data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, selecting participants who had undergone Diffusion Tensor Imaging (DTI) and had registered gender and Mini-Mental State Examination (MMSE) scores. From this subset, we included 54 healthy controls (HC) and 105 AD patients who had completed the Boston Naming Test (BNT) for language function assessment.
Diffusion data were analyzed using DSI-Studio and reconstructed using generalized q-sampling imaging (Yeh et al., 2010). Quantitative anisotropy (QA) was extracted as the local connectome fingerprint (Yeh et al., 2016) and used in the subsequent connectometry analysis. We focused on the right Crus I and Crus II of the cerebellum, performing deterministic fiber tracking to delineate the tracts connecting these regions to the pontine nuclei.
Our analysis consisted of two main steps: 1. Conducting group comparison analysis of the cerebello-pontine tract QA values between AD and HC groups. 2. Performing correlational tractography to investigate the association between the cerebello-pontine tract QA values and BNT scores within each group.
Results:
The QA values of the cerebello-pontine tract connecting Crus I and II to pontine nuclei were significantly lower in AD than HC. Within-group correlation analyses revealed no significant association between BNT scores and QA values in the AD group. In contrast, in the HC group, QA values of the cerebello-pontine tract connecting Crus II to the pontine nuclei showed a significant negative correlation with BNT scores, whereas no such relationship was observed for the tract connecting Crus I to the pontine nuclei.
Conclusions:
This study showed reduced QA values in the cerebello-pontine tract in AD patients compared to HC. Interestingly, in the HC group, lower BNT scores were significantly associated with higher QA values in the tract connecting Crus II to the pontine nuclei. While this may appear contradictory, previous research has suggested that plastic changes occur in the cerebellum (Blumenfeld-Katzir et al., 2011), which could indicate compensatory mechanisms in healthy individuals that are absent in AD patients. Furthermore, as BNT is particularly sensitive to deficits in semantic retrieval, prior fMRI studies have shown that Crus II is strongly associated with semantic processing. These findings suggest that cerebellar involvement in language function warrants further investigation, particularly regarding its role in compensatory plasticity and semantic processing in AD.
Disorders of the Nervous System:
Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s) 1
Language:
Language Other
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
White Matter Anatomy, Fiber Pathways and Connectivity 2
Novel Imaging Acquisition Methods:
Diffusion MRI
Keywords:
Aphasia
Cerebellum
Language
MRI
Neurological
Open Data
WHITE MATTER IMAGING - DTI, HARDI, DSI, ETC
Other - Alzheimer's disease,
1|2Indicates the priority used for review
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Please indicate below if your study was a "resting state" or "task-activation” study.
Other
Healthy subjects only or patients (note that patient studies may also involve healthy subjects):
Patients
Was this research conducted in the United States?
No
Were any human subjects research approved by the relevant Institutional Review Board or ethics panel?
NOTE: Any human subjects studies without IRB approval will be automatically rejected.
Yes
Were any animal research approved by the relevant IACUC or other animal research panel?
NOTE: Any animal studies without IACUC approval will be automatically rejected.
Not applicable
Please indicate which methods were used in your research:
Diffusion MRI
For human MRI, what field strength scanner do you use?
3.0T
Provide references using APA citation style.
Alvarez, M. I., Rivas, L., Lacruz, C., & Toledano, A. (2015). Astroglial cell subtypes in the cerebella of normal adults, elderly adults, and patients with Alzheimer's disease: a histological and immunohistochemical comparison. Glia, 63(2), 287-312.
Blumenfeld-Katzir, T., Pasternak, O., Dagan, M., & Assaf, Y. (2011). Diffusion MRI of structural brain plasticity induced by a learning and memory task. PLOS ONE, 6(6), e20678.
Kinoshita, Y., Hatakeyama, M., Otsuki, M., Ishiguro, T., Saji, E., Kanazawa, M., & Onodera, O. (2024). Cerebellar compensation: a case of aphasia due to cerebellar hemorrhage. Journal of Neurology, 271(6), 3639-3642.
Nakatani, H., Nakamura, Y., & Okanoya, K. (2023). Respective Involvement of the Right Cerebellar Crus I and II in Syntactic and Semantic Processing for Comprehension of Language. Cerebellum, 22(4), 739-755.
Yang, C., Liu, G., Chen, X., & Le, W. (2024). Cerebellum in Alzheimer's disease and other neurodegenerative diseases: an emerging research frontier. MedComm (2020), 5(7), e638.
Yeh, F.-C., Wedeen, V., & Tseng, W.-Y. (2010). Generalized Q-Sampling Imaging. Medical Imaging, IEEE Transactions on, 1626-1635.
Yeh, F. C., Vettel, J. M., Singh, A., Poczos, B., Grafton, S. T., Erickson, K. I.,…Verstynen, T. D. (2016). Quantifying Differences and Similarities in Whole-Brain White Matter Architecture Using Local Connectome Fingerprints. PLoS Comput Biol, 12(11), e1005203.
Zheng, W., Liu, X., Song, H., Li, K., & Wang, Z. (2017). Altered Functional Connectivity of Cognitive-Related Cerebellar Subregions in Alzheimer's Disease. Front Aging Neurosci, 9, 143.
No