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Altered neuro-substrates preceding accelerated cognitive and mobility aging in older people

Poster No:

1134

Submission Type:

Abstract Submission

Authors:

Pei-Lin Lee¹, Kun-Hsien Chou²^,3, Chih-Kuang Liang⁴^,5^,1, Chih-Ping Chung¹^,6, Wei-Ju Lee¹^,7, Li-Ning Peng¹^,8, Liang-Kung Chen¹^,8^,9, Ching-Po Lin²^,3^,10

Institutions:

¹Center for Healthy Longevity and Aging Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan, ²Institute of Neuroscience, National Yang Ming Chiao Tung University, Taipei, Taiwan, ³Brain Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan, ⁴Center for Geriatrics and Gerontology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, ⁵Division of Neurology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, ⁶Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan, ⁷Department of Family Medicine, Taipei Veterans General Hospital Yuanshan Branch, Yi-Lan, Taiwan, ⁸Center for Geriatric and Gerontology, Taipei Veterans General Hospital, Taipei, Taiwan, ⁹Taipei Municipal Gan-Dau Hospital (managed by Taipei Veterans General Hospital), Taipei, Taiwan, ¹⁰Department of Education and Research, Taipei City Hospital, Taipei, Taiwan

First Author:

Pei-Lin Lee
Center for Healthy Longevity and Aging Sciences, National Yang Ming Chiao Tung University
Taipei, Taiwan

Co-Author(s):

Kun-Hsien Chou
Institute of Neuroscience, National Yang Ming Chiao Tung University|Brain Research Center, National Yang Ming Chiao Tung University
Taipei, Taiwan|Taipei, Taiwan

Chih-Kuang Liang
Center for Geriatrics and Gerontology, Kaohsiung Veterans General Hospital|Division of Neurology, Department of Internal Medicine, Kaohsiung Veterans General Hospital|Center for Healthy Longevity and Aging Sciences, National Yang Ming Chiao Tung University
Kaohsiung, Taiwan|Kaohsiung, Taiwan|Taipei, Taiwan

Chih-Ping Chung
Center for Healthy Longevity and Aging Sciences, National Yang Ming Chiao Tung University|Department of Neurology, Neurological Institute, Taipei Veterans General Hospital
Taipei, Taiwan|Taipei, Taiwan

Wei-Ju Lee
Center for Healthy Longevity and Aging Sciences, National Yang Ming Chiao Tung University|Department of Family Medicine, Taipei Veterans General Hospital Yuanshan Branch
Taipei, Taiwan|Yi-Lan, Taiwan

Li-Ning Peng
Center for Healthy Longevity and Aging Sciences, National Yang Ming Chiao Tung University|Center for Geriatric and Gerontology, Taipei Veterans General Hospital
Taipei, Taiwan|Taipei, Taiwan

Liang-Kung Chen
Center for Healthy Longevity and Aging Sciences, National Yang Ming Chiao Tung University|Center for Geriatric and Gerontology, Taipei Veterans General Hospital|Taipei Municipal Gan-Dau Hospital (managed by Taipei Veterans General Hospital)
Taipei, Taiwan|Taipei, Taiwan|Taipei, Taiwan

Ching-Po Lin
Institute of Neuroscience, National Yang Ming Chiao Tung University|Brain Research Center, National Yang Ming Chiao Tung University|Department of Education and Research, Taipei City Hospital
Taipei, Taiwan|Taipei, Taiwan|Taipei, Taiwan

Introduction:

Concurrent cognitive and mobility impairments, a condition known as physio-cognitive decline syndrome (PCDS), brings higher risks of dementia and mortality in older people [1]. Previous cross-sectional studies have identified specific clinical and neuroanatomic features linked to PCDS, indicating its potential as distinct preclinical dementia syndrome. However, the temporal relationship between neuroanatomic abnormalities and the development of PCDS has not yet been investigated. Understanding the neuroanatomical alterations preceding this syndrome is crucial for understanding the early pathophysiology of PCDS. This longitudinal study aimed to examine grey-matter volumes (GMV) and the corresponding structural covariance network (SCN) abnormalities in robust individuals to predict the conversion to PCDS.

Methods:

Participants were sourced from the I-Lan Aging Longitudinal Study [2], comprising robust individuals with no initial signs of PCDS. Participants were categorized into PCDS-converter and non-PCDS converter groups based on their status in the follow-up clinical assessment. The image analytical pipeline was shown in Fig 1A. Baseline T1w images were preprocessed with the VBM pipeline under CAT12 [3]. Voxel-wise ANCOVA model, accounting for age, sex, education, smoking status, and total intracranial volume, was applied to identify the regional GMV alterations. These regions served as seeds in subsequent seed-to-voxel SCN analysis to establish corresponding morphometric networks. Significant SCN changes between groups were identified using a linear regression model with a group by mean seed volume interaction term. Furthermore, individual inter-regional SC integrity was calculated using a jackknife bias estimation procedure [4] for further correlation analysis. Regional GMV and individual SCN integrity that showed abnormalities in the PCDS converter group were further analyzed for their associations with physical and cognitive performance at follow-up, using the partial Spearman correlation analysis with the same nuisance variables.

Results:

The study included 343 robust individuals (60.2±6.9 years old, 49.6% men). After an average follow-up period of 5.6 years, 227 remained non-PCDS, while 116 converted to PCDS. Notable GMV reduction were identified in the cerebellum and right caudate among PCDS converters (see Fig 1B). Significant differences in SCNs between study groups for cerebellum-based (to right frontal-pole and left middle-frontal-gyrus) and caudate-based SCNs (to right caudate-putamen, right planum-temporale, left precentral-gyrus, right postcentral-gyrus, and left parietal-operculum) were observed (see Fig 1C). Furthermore, correlation analysis revealed the cerebellum's regional GMV and the integrity of the caudate-based SCNs at baseline might be linked to certain physical examination and cognitive performance at follow-up (with uncorrected p<0.05, see Fig 2).

Conclusions:

The study uncovered early regional GMV and morphological network changes preceding PCDS in community-dwelling older individuals. PCDS converters exhibited baseline GMV reductions in cerebellum and increases right caudate volumes compared to non-converters. Seed-to-voxel SCN analysis identified distinct covariances in two cerebellum-based (to right frontal-pole and left middle-frontal-gyrus) and caudate-based SCNs (to right caudate-putamen, right planum-temporale, left precentral-gyrus, right postcentral-gyrus, and left parietal-operculum) between groups. These identified regional GMV and SCNs' integrity at baseline were also linked to physical mobility and cognitive performances over time. These findings offer an understanding of the neuroanatomical foundation of rapid declines in both physical mobility and cognitive functions, potentially guiding targeted prevention of subsequent dementia in those older people with dual cognitive and mobility impairments.

Disorders of the Nervous System:

Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s) ²

Lifespan Development:

Aging ¹

Keywords:

Aging

STRUCTURAL MRI

^1|2Indicates the priority used for review

·Fig 1

·Fig 2

Provide references using author date format

[1] Chung, C-P., et al. "Physio-cognitive decline syndrome as the phenotype and treatment target of unhealthy aging." The journal of nutrition, health & aging (2021): 1-11.
[2] Lee, Wei-Ju, et al. "Comparisons of sarcopenia defined by IWGS and EWGSOP criteria among older people: results from the I-Lan longitudinal aging study." Journal of the American medical directors association 14.7 (2013): 528-e1.
[3] Gaser, Christian, et al. "CAT–A computational anatomy toolbox for the analysis of structural MRI data." biorxiv (2022): 2022-06.
[4] Yang, Crystal C., et al. "Sex differences in cognition and structural covariance-based morphometric connectivity: evidence from 28,000+ UK Biobank participants." Cerebral Cortex 33.19 (2023): 10341-10354.