Brain Structural Changes Underlying Hyposmia across Parkinson's and Alzheimer's Disease Spectra
Poster No:
88
Submission Type:
Abstract Submission
Authors:
Zhengui Yang1, Hiroki Togo1, Takashi Hanakawa1
Institutions:
1Kyoto University, Kyoto, Kyoto
First Author:
Co-Author(s):
Introduction:
Many studies have reported olfactory dysfunction (OD) as an early symptom of Alzheimer's disease (AD) and Parkinson's disease (PD). However, these lines of research may not have fully captured the shared or differential mechanisms underlying OD in AD and PD because they investigated AD and PD independently. AD is a disease spectrum, including preclinical AD and mild cognitive impairment (MCI), with memory impairment being the primary characteristic that progresses over time. PD is characterized clinically by motor dysfunction and pathologically by the Lewy body, thereby constituting Lewy body disease (LBD) spectra, including Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB). However, recent evidence indicates a substantial overlap between AD and LBD spectra; for example, many patients with DLB have deposition of amyloid β, a molecular hallmark of AD. To better understand the mechanisms of OD, we aimed to examine the correlation of OD with cognitive impairment and motor dysfunction in AD and LDB spectra and to identify the shared or spectrum-specific brain regions involved.
Methods:
We analyzed datasets of 223 participants (69.9±8.6 years, meanstandard deviation) from the Parkinson's and Alzheimer's disease Dimensional Neuroimaging Initiative (PADNI), a multi-center cohort study recruiting clinically diagnosed AD, PD, and healthy aged controls. All participants underwent the odor stick identification test for Japanese (OSIT-J) to assess OD. We used the Unified Parkinson's Disease Rating Scale Part III to define movement disorder (M+) and Clinical Dementia Rating to define cognitive impairment (C+). The participants were divided into four groups: C+M+ group (n = 36), C+M- group (n = 57), M+C- group (n = 61), and C-M- group (n = 69). T1-weighted, 3-dimensional structural MRI was acquired on a 3-T scanner (Siemens, Erlangen, Germany). Gray matter volume (GMV) was calculated using a voxel-based morphometry (VBM) algorithm provided by the Computational Anatomy Toolbox. The ComBat method was applied to address differences in the study site. Correlation analyses tested the relationship between GMV and OD, as assessed by OSIT-J.
Results:
Compared to the C-M- group, C+M- and M+C- groups showed comparable OD, and the C+M+ group showed even more reduced OSIT-J score (C+M+: 3.6±2.9; C+M-: 5.0±3.0; M+C-: 5.7±3.1; C-M-:9.4±2.8). Two-way ANOVA revealed significant main effects of cognitive impairments (p<0.001) and motor dysfunction (p<0.001) on olfactory scores, as well as a significant interaction between the two factors (p=0.006). The whole-brain VBM analysis found a correlation between OD and GMV loss in the bilateral amygdala, hippocampus, entorhinal cortex, middle cingulate gyrus and left middle frontal gyrus across the groups (FWE corrected at p<0.05). In analyses within each group, similar correlations in bilateral amygdala, hippocampus, and entorhinal cortex were observed only in the C+M- group. Notably, changes in GMV associated with olfactory function were observed only in the cognitive impairment group, with no correlation found between GMV reduction and motor dysfunction concerning olfactory deficits.
·Brain atrophy related to olfactory function in the C+/M- group.
Conclusions:
These results indicate that mechanisms underlying cognitive impairment and motor dysfunction in AD and DLB spectra distinctly contribute to OD. Cognitive impairment likely coexists with OD through the impairment of the medial temporal cortex responsible for olfactory and cognitive processing. In contrast, the neural mechanisms underlying the association between motor dysfunction and OD remain to be further explored. Understanding these distinct yet interconnected mechanisms is essential for the early diagnosis of AD and DLB spectra, eventually leading to targeted disease-modifying interventions.
Disorders of the Nervous System:
Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s) 1
Novel Imaging Acquisition Methods:
Anatomical MRI
Perception, Attention and Motor Behavior:
Chemical Senses: Olfaction, Taste 2
Keywords:
Cognition
Motor
STRUCTURAL MRI
Other - Olfactory Dysfunction, Neurodegenerative Disease
1|2Indicates the priority used for review
Abstract Information
By submitting your proposal, you grant permission for the Organization for Human Brain Mapping (OHBM) to distribute your work in any format, including video, audio print and electronic text through OHBM OnDemand, social media channels, the OHBM website, or other electronic publications and media.
The Open Science Special Interest Group (OSSIG) is introducing a reproducibility challenge for OHBM 2025. This new initiative aims to enhance the reproducibility of scientific results and foster collaborations between labs. Teams will consist of a “source” party and a “reproducing” party, and will be evaluated on the success of their replication, the openness of the source work, and additional deliverables. Click here for more information. Propose your OHBM abstract(s) as source work for future OHBM meetings by selecting one of the following options:
Please indicate below if your study was a "resting state" or "task-activation” study.
Healthy subjects only or patients (note that patient studies may also involve healthy subjects):
Was this research conducted in the United States?
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.
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.
Please indicate which methods were used in your research:
For human MRI, what field strength scanner do you use?
Which processing packages did you use for your study?
Provide references using APA citation style.
2. Baba, T., Takeda, A., Kikuchi, A., Nishio, Y., Hosokai, Y., Hirayama, K., Hasegawa, T., Sugeno, N., Suzuki, K., Mori, E., Takahashi, S., Fukuda, H., & Itoyama, Y. (2011). Association of olfactory dysfunction and brain. Metabolism in Parkinson's disease. Movement disorders : official journal of the Movement Disorder Society, 26(4), 621–628.
3. Marin, C., Vilas, D., Langdon, C., Alobid, I., López-Chacón, M., Haehner, A., Hummel, T., & Mullol, J. (2018). Olfactory Dysfunction in Neurodegenerative Diseases. Current allergy and asthma reports, 18(8), 42.
4. Tian, Q., Resnick, S. M., & Studenski, S. A. (2017). Olfaction Is Related to Motor Function in Older Adults. The journals of gerontology. Series A, Biological sciences and medical sciences, 72(8), 1067–1071.
5. Risacher, S. L., & Saykin, A. J. (2019). Neuroimaging in aging and neurologic diseases. Handbook of clinical neurology, 167, 191–227.
6. Fortin, J. P., Cullen, N., Sheline, Y. I., Taylor, W. D., Aselcioglu, I., Cook, P. A., Adams, P., Cooper, C., Fava, M., McGrath, P. J., McInnis, M., Phillips, M. L., Trivedi, M. H., Weissman, M. M., & Shinohara, R. T. (2018). Harmonization of cortical thickness measurements across scanners and sites. NeuroImage, 167, 104–120.