Research Presentation Session: Neuro

RPS 2111 - Neurodegeneration and cognition

March 2, 16:00 - 17:30 CET

7 min
Relationship between hippocampal subfield volumes and cognitive decline in healthy subjects
Simon Doran, Dublin / Ireland
Author Block: S. Doran, R. A. Kenny, J. F. Meaney, C. De Looze; Dublin/IE
Purpose: We examined the relationship between hippocampal subfield volumes and cognitive decline over a four-year period in a healthy older adult population with the goal of identifying subjects at risk of progressive cognitive impairment which could potentially guide therapeutic interventions and monitoring.
Methods or Background: 482 subjects (68.1 years +/- 7.4; 52.9% female) from the Irish Longitudinal Study on Ageing underwent magnetic resonance brain imaging and a series of cognitive tests. Using K-means longitudinal clustering, subjects were first grouped into three separate global and domain-specific cognitive function trajectories; high-stable, mid-stable and low-declining. Linear mixed effects models were then used to establish associations between hippocampal subfield volumes and cognitive groups.
Results or Findings: Decline in multiple hippocampal subfields was associated with global cognitive decline, specifically the presubiculum (estimate -0.20; 95% confidence interval (CI) -0.78 – -0.02; p=.03), subiculum (-0.44; -0.82 – -0.06; p=.02), CA1 (-0.34; -0.78 – -0.02; p=.04), CA4 (-0.55; -0.93 – -0.17; p=.005), molecular layer (-0.49; -0.87 – -0.11; p=.01), dentate gyrus (-0.57; -0.94 – -0.19; p=.003), hippocampal tail (-0.53; -0.91 – -0.15; p=.006) and HATA (-0.41; -0.79 – -0.03; p=.04), with smaller volumes for the Low-Declining cognition group compared to the High-Stable cognition group. In contrast to global cognitive decline, when specifically assessing the memory domain, cornu ammonis 1 subfield was not found to be associated with low declining cognition (-0.14; -0.37 – 0.10; p=.26).
Conclusion: Previously published data shows that atrophy of specific hippocampal subfields is associated with cognitive decline but our study confirms the same effect in subjects asymptomatic at time of enrolment. This strengthens the predictive value of hippocampal subfield atrophy in risk of cognitive decline and may provide a biomarker for monitoring treatment efficacy.
Limitations: T1 imaging can be unreliable for hippocampal segmentation.
Funding for this study: Funding for The Irish Longitudinal Study on Ageing (TILDA) is provided by the Irish Government, the Health Research Board (HRB), The Atlantic Philanthropies, and the Irish Life Plc.
Has your study been approved by an ethics committee? Yes
Ethics committee - additional information: This study was approved by the Trinity College Faculty of Health Sciences Research Ethics Committee, Dublin, Ireland. Protocols conformed with the Declaration of Helsinki. Signed informed consent was obtained from all respondents prior to participation. Additional ethics approval was received for the magnetic resonance imaging (MRI) sub-study from the St James’s Hospital/Adelaide and Meath Hospital, Inc. National Children’s Hospital, Tallaght (SJH/AMNCH) Research Ethic Committee, Dublin, Ireland. Those attending for MRI also completed an additional MRI-specific consent form. (De Looze et al)
7 min
Differential atrophy along the longitudinal axis of the hippocampus in Alzheimer’s disease and suspected non-Alzheimer’s disease pathophysiology (SNAP)
Torcato Meira, Braga / Portugal
Author Block: T. Meira, R. Morais-Ribeiro, T. Jesus, M. Dias, A. Coelho, T. G. Oliveira; Braga/PT
Purpose: Cerebrospinal fluid (CSF) biomarkers have been increasingly used to support diagnosis of Alzheimer’s disease (AD). Suspected non-AD pathophysiology (SNAP) refers to normal CSF levels of amyloid-beta (AB) with increased tau, whereas Alzheimer’s Disease continuum (ADc) is defined by AB pathology evidence. Since hippocampus studies have highlighted differential properties along its longitudinal axis, we aim to evaluate how its various subregional volumetric markers differ between ADc, SNAP and controls, as well as their association with clinical presentation.
Methods or Background: We included 1242 participants from the Alzheimer’s Disease Neuroimaging Initiative. Controls (n=234) were defined as having normal CSF AB (≥192 pg/ml), total tau (<93 pg/ml) and phosphorylated tau (<23 pg/ml). ADc individuals (n=784) were abnormal for AB, whereas SNAP subjects (n=224) had normal AB with either abnormal total or phosphorylated tau. Structural MRI acquisitions were analyzed with a method developed in our laboratory for segmenting the hippocampus in anterior, intermediate and posterior parts. Controlling for age, sex and multiple comparisons, groups were compared with one-way ANOVA and Pearson coefficients were calculated to assess correlations between volumetric variables and age, CSF biomarkers or neuropsychological scores.
Results or Findings: ADc showed lower total and subregional hippocampal volumes than SNAP or controls (P<0.001). When normalizing the volume of each subregion for its total ipsilateral hippocampus volume, ADc showed increased posterior atrophy (P<0.001) and higher relative anterior volume (P<0.01) when compared to the other groups. SNAP and controls showed greater correlations between volumetric measures and age, with attenuated differences over age. Several subregional hippocampal volumes correlated significantly with altered levels of CSF biomarkers, cognition, neuropsychiatric features and functional impairment.
Conclusion: Our work contributes to better understanding of ADc and SNAP pathophysiology and to predicting their respective clinical features.
Limitations: No limitations were identified.
Funding for this study: No funding was received for this study.
Has your study been approved by an ethics committee? Yes
Ethics committee - additional information: As per ADNI protocols, all procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. More details can be found at adni.loni.usc.edu.
7 min
Grey matter atrophy mediates the association between tau pathology and cognition in Alzheimer's disease: a simultaneous PET/MRI study
Xinru Xu, Nanjing / China
Author Block: X. Xu, B. Zhang; Nanjing/CN
Purpose: This study aimed to investigate the area-specific causal pathways between regional tau pathology, grey matter atrophy, and cognitive impairment in MCI/AD patients.
Methods or Background: Thirty-four MCI/AD patients covering the prodromal to dementia spectrum and 23 cognitive normal controls experienced standardised neuropsychological assessments followed by 18F-fortaucipir (FTP) PET and 3D T1 magnetic resonance imaging (MRI). We explored voxel-wise and region of interest- based inter-group differences in grey matter volume (GMV) and regional tau standardised uptake value ratio (SUVR) in the two groups. Multimodal correlation analyses and mediation analyses were carried out to assess the relationship between GMV and the SUVR and cognition scores in MCI/AD group.
Results or Findings: The 18F-fortaucipir retention was observed in the fusiform, lateral temporal lobe, supramarginal gyrus, precuneus and posterior cingulate in MCI/AD groups. Mediation analyses showed the GMV of the medial parietal lobes and medial temporal lobes mediated the effect of local and distant region tau on cognitive impairment. Besides, in the medial temporal, GMV of the entorhinal cortex mediated the effect of local region tau on cognitive impairment.
Conclusion: Our finding help to clarify the spatial relationship of tau propagation and gray matter atrophy. Local and distant atrophy played a important mediating role between tauand cognitive impairment in MCI/AD patients. Besides, temporoparietal region is an important hub linking gray matter atrophy, tau pathology, and cognitive impairment for AD, and might be a potential treatment target region for AD.
Limitations: Firstly, the 18F-fortaucipir PET tracer demonstrating a low degree of off-target binding in the choroid plexus may lead to inaccurate quantification of tau protein in the hippocampus ,Another limitation is the small sample size, longitudinal measurements utilising a larger sample size will be conducted in future studies.
Funding for this study: This work was supported by Clinical Research Special Funded Project of Nanjing Drum Tower Hospital (No. 2023-LCYJ-MS-11).
Has your study been approved by an ethics committee? Yes
Ethics committee - additional information: Northern Theater General Hospital Ethics Committee: No.2021(024).
7 min
Compensatory deregulation of attention and executive networks in prodromal Lewy body dementia. A resting-state functional magnetic resonance imaging study
Valeria Onofrj, Rome / Italy
Author Block: V. Onofrj1, R. Franciotti2, A. Ferretti2, C. Padulo2, S. Sansi2, I. Rektorova3; 1Brussels/IT, 2Chieti/IT, 3Brno/CZ
Purpose: Early diagnosis of Lewy Body Dementia (MCI-LBD) is challenging due to the lack of specific diagnostic tests and imaging findings. MCI-LBD subjects show attentional, executive, spatial perception, verbal, spatial memory, and intelligence deficits. These occur early and imply the dysfunction of selected sensory and associative networks.
Methods or Background: We performed a global analysis of resting-state functional MRI data on 38 MCI-LBD subjects and 24 healthy controls (HC) and extracted the connectivity matrices of regions included in the Cingulo-opercular Network (CON), Fronto-Parietal Network (FPN), Default Mode Network (DMN), Dorsal Attention Network (DAN), Somato-Motor Network (SMN), Visual Network (VN) and Language Network (LN). We compared intra- and inter-network connectivity between the two groups of subjects and correlated neuropsychological test scores with intra- and inter-network connectivity of MCI-LBD subjects.
Results or Findings: The data revealed increased between-networks connectivity (p<0.05) between the DAN and SMN, the CON and FPN, and the FPN and DMN in MCI-LBD subjects vs. HC. Decreased between-network and intra-network connectivity (p<0.05) was found between the SMN and DMN, the DMN and DAN, and between the right rostral prefrontal and right anterior insular nodes of the CON in MCI-LBD subjects vs. HC. Significant correlations (p<0.05) were found among intra-network and between-network FC values and attention, executive, visuo-perceptual, verbal memory, spatial memory deficit, and intelligence tests.
Conclusion: Overall, we found early demodulation of intra- and inter-network connectivity starting with the internal dissociation of the CON. Intra- and inter-network connectivity correlates with neuropsychological tests results and may potentially serve as early imaging biomarkers of LBD.
Limitations: Our study limitation is mainly the limited number of subjects.
Funding for this study: The authors received no financial support for the research, authorship, and publication of this article.
Has your study been approved by an ethics committee? Yes
Ethics committee - additional information: This study was approved by the Ethics Committee of Masaryk University and was performed according to the Declaration of Helsinki (1997) and subsequent revisions. All participants gave written informed consent.
7 min
Can AI augmented MRI replace FDG PET CT brain in the evaluation of patients with cognitive impairment
Henry Dillon, Dublin / Ireland
Author Block: H. Dillon, B. S. Kelly, G. J. Mcneill, R. O'Donohoe, A. Stone, C. Hickie, M. Colombie, J. Kinsella, R. P. Killeen; Dublin/IE
Purpose: Cerebral atrophy and hypometabolism are crucial indicators of neurodegenerative diseases such as Alzheimer's and other cognitive disorders. Assessing cerebral atrophy on MRI is time consuming and subjective. This study aims to compare cerebral atrophy detected on AI augmented MRI with patterns of hypometabolism on FDG PET brain, the current gold standard. This software has the potential to reduce the need for costly FDG PET brain studies as well as increase the number of radiologists who can interpret neurodegenerative studies.
Methods or Background: There is currently limited availability of FDG PET brain in the diagnosis of neurodegenerative conditions worldwide. A new commercially available AI software available through Siemens known as RadCompanion utilises artificial intelligence to detect cerebral atrophy on T1w MRI brain using a simplistic traffic light colour coded system while also providing quantitative analyses. We compared atrophy detected on this new software with the pattern of hypometabolism on FDG PET brain. The images were interpreted by a dual specialised neuromolecular radiologist, specialist neuroradiologist and neuroradiology fellow.
Results or Findings: Twenty-three patients were assessed. The patten of cerebral atrophy on MRI was compared to corresponding FDG PET brain and a pattern of neurodegeneration suggested. In 78% of patients the pattern of neurodegeneration suggested matched the suggested diagnosis on the corresponding FDG PET brain. In 100% of patients a normal MRI correlated with a normal FDG PET brain.
Conclusion: Our study demonstrates good correlation between AI augmented MRI and FDG PET Brain. This software could provide a useful screening test in centres with limited availability to PET CT and perhaps a suitable alternative in centres with no access. We recommend further evaluation in future using a larger sample size.
Limitations: Limitations included small sample size, single centre and retrospective study.
Funding for this study: No funding was obtained for this study.
Has your study been approved by an ethics committee? Not applicable
Ethics committee - additional information: This study as ethically approved by through local hospital audit committee.
7 min
Brain tissue atrophy and cognitive decline in relation to serum uric acid variance
Jing Sun, Beijing / China
Author Block: J. Sun, H. Lv, Z. Wang; Beijing/CN
Purpose: This study aimed to evaluate the long-term associations between serum uric acid (SUA) variance and neuroimaging indices of brain health.
Methods or Background: This cohort study recruited 1,111 participants aged 25-83 years from the subset study of brain MRI acquisition within the Kailuan study from 2020 onward. The SUA concentrations were measured every two years from 2006 to 2018. We primarily assessed SUA variance as the average slope incorporating seven measurements and further defined the direction of changes. The multivariate-adjusted associations of SUA variance with MRI markers of brain tissue volumes and microstructural integrity and cognitive function were examined using generalised linear models.
Results or Findings: Compared with the stable group, brain white matter (WM) volume decreased irrespective of the increase or decrease in SUA levels (beta=−0.26, 95% CI −0.40 to 0.12 and beta=−0.15, 95% CI −0.28 to −0.02). Elevated SUA levels were also associated with smaller cerebral parenchyma volume (beta=−0.01, 95% CI −0.01 to 0). Participants with progressively increased SUA levels exhibited lower global fractional anisotropy and higher radial diffusivity (beta=−0.27, 95% CI −0.41 to −0.13 and beta=0.23, 95% CI 0.10 to 0.36), which remained significant after further adjustment for white matter and white matter hyperintensity volume. Elevated SUA concentration was also associated with lower MoCA scores (beta=−0.20, 95% CI −0.33 to −0.06).
Conclusion: The SUA changes were associated with decreased WM volume. Progressively increased SUA levels detrimentally affect brain health, manifested by smaller brain tissue volume, impaired microstructural integrity, and poorer cognitive performance. Long-term prevention of SUA fluctuation is essential for protecting brain health and preventing early-stage dementia.
Limitations: The effects of SUA variance in a more recent period on neuroanatomical features were still unknown and warrant future exploration.
Funding for this study: This study was supported by grants No. 62171297 and 61931013 from the National Natural Science Foundation of China, No. [2015] 160 from the Beijing Scholars Program, No. ZYLX202101 from Beijing Hospitals Authority Clinical Medicine Development of Special Funding Support, No. 2021-135 from Beijing Municipal Health Commission-Beijing Key Clinical Discipline Funding.
Has your study been approved by an ethics committee? Yes
Ethics committee - additional information: The META-KLS cohort study was ethically approved by the Medical Ethics Committee of Kailuan General Hospital (No.2021002). Written informed consent was obtained from all participants. Participants did not receive a stipend.
7 min
White matter abnormalities in patients with mild cognitive impairment and post-acute sequelae of COVID- 19: preliminary results of a radiomics study
Melania Stubos, Trieste / Italy
Author Block: M. Stubos, M. Ukmar, G. Pizzamiglio, I. Zorzenon, L. Bottaro, E. Zulian, N. Fiotti, G. Furlanis, M. A. A. Cova; Trieste/IT
Purpose: The purpose of this study was to assess the contribution of radiomics in the analysis of the normal appearing white matter (NAWM) in patients with cognitive decline related to mild cognitive impairment (MCI) and to post-acute sequelae of COVID-19 (PASC) in comparison to the normal white matter (NMW) of healthy controls. Furthermore, we compared the NAMW of the patients with MCI to the one of patients with PASC.
Methods or Background: A retrospective study on ten patients with MCI, ten patients with PASC and 23 healthy controls who underwent a 3T MRI was performed, and the 3D-FLAIR sequence was selected. Fourteen different brain areas (bilateral frontal lobes, temporal lobes, parietal lobes, thalami, cerebellar peduncles, lateral ventricles, and genu and splenium of the corpus callosum) were selected for the ROIs placement: features were extracted on a radiomics software and a statistical analysis was carried out through a binary logistic regression model.
Results or Findings: In the comparison between the NAWM of MCI patients and the NWM of healthy controls, statistically significant differences (p<0.05) were found in all the 14 analysed areas, with a good performance in the temporal, frontal and parietal lobes. Significant differences were also found in the comparison between the NAWM of PASC patients and the NWM of healthy controls, with a good performance in the frontal lobes, temporal lobes and thalami. No significant differences were found in the comparison between the NAWM of patients with MCI and PASC.
Conclusion: This study shows that radiomics can be a useful tool in the analysis of the NAMW in patients with cognitive decline related to MCI and PASC.
Limitations: The low number of patients included in the study and the heterogeneity of the MCI group of patients.
Funding for this study: No funding was received for this study.
Has your study been approved by an ethics committee? Not applicable
Ethics committee - additional information: The study is retrospective study, hence ethical approval was not sought.
7 min
COVID-19 induces grey matter atrophy in patients with cognitive but also with only olfactory disorders
Simonetta Gerevini, Cremona / Italy
Author Block: S. Capelli1, A. Caroli1, A. Arrigoni1, A. Napolitano2, G. Pezzetti2, A. Remuzzi3, F. L. Lorini2, M. Sessa2, S. Gerevini2; 1Ranica/IT, 2Bergamo/IT, 3Dalmine/IT
Purpose: The aim of this study was to evaluate grey matter (GM) structural alterations related to COVID-19 in two separate groups of patients with the most frequent and distinctive COVID-19-related neurological manifestations - isolated olfactory disorders (COVID-OD) and cognitive disorders (COVID-CM) – compared to a control group of healthy individuals.
Methods or Background: Sixty-one COVID-CM patients (57[60–63] years, 62% females), 84 COVID-OD patients (49[35–57] years, 60% females) and 17 controls (51[41–52] years, 41% females) were included in the study. To investigate differences between patients and controls in terms of GM regional volume and voxel-wise density, Region-Based Morphometry (RBM) and Voxel-Based Morphometry (VBM) were applied to T1-weighted MRI scans. Surface-Based Morphometry (SBM) was used to investigate changes in cortical thickness.
Total intracranial volume and age were included as nuisance variables in the statistical model assessing group differences.
Results or Findings: The multi-morphometric analysis revealed statistically significant reduction in GM regional volume (RBM) and density (VBM) as well as lower cortical thickness in both COVID-CM and COVID-OD groups compared to controls. Notably, COVID-CM patients showed more widespread and severe tissue loss than COVID-OD patients.
The most affected GM regions were hippocampus, putamen, cingulate cortex, praecuneus, amygdala, lingual gyrus, and caudate nucleus. Most of the atrophic regions are known to be involved in memory processes, in the sense of smell, or both.
Conclusion: Current MRI findings indicate that, with varying degrees of severity, both COVID-19-related olfactory and cognitive disorders lead to GM atrophy, possibly reflecting neurodegeneration and neuroinflammation. The COVID-CM group showed more pronounced GM changes, suggesting a stronger inflammatory response.
Limitations: This was a retrospective and monocentric study, with a small control population. Quantitative clinical data assessing the severity of olfactory or cognitive disorders was not available.
Funding for this study: This study received partial support from Brembo SpA (Curno, Bergamo, Italy) through the "Progetto TrexUno" initiative.
Has your study been approved by an ethics committee? Yes
Ethics committee - additional information: The use of patient data was granted ethical approval by the local ethics committee as part of a broader observational study protocol (Reg. 118/22). Informed consent was acquired from patients or from their next of kin (in the case of ICU patients).
7 min
Brain age in healthy individuals and across multiple neurological disorders
Li Chai, Beijing / China
Author Block: L. Chai, Z. Zhuo, Y. Duan, Y. Liu; Beijing/CN
Purpose: The aim of this study was to investigate brain age in healthy individuals and across multiple neurological disorders and its association with MRI measures and clinical variables.
Methods or Background: MRI and clinical data of 2,913 HC and 331 MS patients, 189 NMOSD patients, 239 AD patients, 244 PD patients, and 338 cSVD patients were collected. Brain age gap (BAG) was defined as the difference between brain age predicted using 3D T1w with deep learning and chronological age. Brain regions volumes and WMH and clinical measures were compared between HC with advanced brain aging (BAG ≥ 5 years) and resilient brain agers (BAG ≤ −5 years). Associations between BAG, WMH and clinical variables were examined in patients.
Results or Findings: Increased BAG was in patients with MS (10.30 ± 12.6 years), NMOSD (2.96 ± 7.8 years), AD (6.50 ± 6.6 years), PD (4.24 ± 4.8 years), and cSVD (3.24 ± 5.9 years). WMH was higher and regional brain volume was lower in advanced brain agers (p <0.001) than in resilient brain agers. The specific brain regions associated with increased BAG differed across the various neurological disorders. Increased BAG was correlated with WMH and cognitive decline in neurological disorders. Increased BAG was correlated with higher disability scores in MS patients but not in NMOSD patients.
Conclusion: The BAG shows utility as an imaging marker for monitoring cognitive and physical impairment across different neurological disorders. Advanced brain age was associated with atrophy and WMH, suggesting an increased risk of neurological problems.
Limitations: First, it was cross-sectional study. Second, deep learning methods are a “black box”, and the interpretability of brain age predictions needs further improvement. Third, we did not consider other factors that influence brain age. Fourth, the cognitive and clinical assessments were relatively limited.
Funding for this study: This study was funded by the Beijing Tiantan Hospital, Capital Medical University, No. KY-2019-050-02 and KY-2019-140-02.
Has your study been approved by an ethics committee? Yes
Ethics committee - additional information: This study was ethically approved by the Beijing Tiantan Hospital, Capital Medical University, No. KY-2019-050-02 and KY-2019-140-02.

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