Brain Network Disruptions in Young to Middle-Aged Adults with Subjective Memory Complaints
Poster No:
1437
Submission Type:
Abstract Submission
Authors:
WAN CHUN YANG1, Chia-Lin Tsai2, Pei-Lin Lee3, Chih-Sung Liang4, Yu-Kai Lin2, Guan-Yu Lin2, Yi-Chih Hsu5, Lin Ching-Po6, Fu-Chi Yang2, Kun-Hsien Chou7
Institutions:
1National Yang Ming Chiao Tung University / National Health Research Institutes, Taipei, Taiwan, 2Department of Neurology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, 3National Yang Ming Chiao Tung University, Taipei, N/A, 4Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taiper, Taiwan, 5Department of Radiology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, 6Department of Education and Research, Taipei City Hospital, Taipei, Taiwan, 7Brain research center, National Yang Ming Chiao Tung University, Taipei, Taiwan
First Author:
WAN CHUN YANG
National Yang Ming Chiao Tung University / National Health Research Institutes
Taipei, Taiwan
National Yang Ming Chiao Tung University / National Health Research Institutes
Taipei, Taiwan
Co-Author(s):
Chia-Lin Tsai
Department of Neurology, Tri-Service General Hospital, National Defense Medical Center
Taipei, Taiwan
Department of Neurology, Tri-Service General Hospital, National Defense Medical Center
Taipei, Taiwan
Chih-Sung Liang
Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center
Taiper, Taiwan
Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center
Taiper, Taiwan
Yu-Kai Lin
Department of Neurology, Tri-Service General Hospital, National Defense Medical Center
Taipei, Taiwan
Department of Neurology, Tri-Service General Hospital, National Defense Medical Center
Taipei, Taiwan
Guan-Yu Lin
Department of Neurology, Tri-Service General Hospital, National Defense Medical Center
Taipei, Taiwan
Department of Neurology, Tri-Service General Hospital, National Defense Medical Center
Taipei, Taiwan
Yi-Chih Hsu
Department of Radiology, Tri-Service General Hospital, National Defense Medical Center
Taipei, Taiwan
Department of Radiology, Tri-Service General Hospital, National Defense Medical Center
Taipei, Taiwan
Fu-Chi Yang
Department of Neurology, Tri-Service General Hospital, National Defense Medical Center
Taipei, Taiwan
Department of Neurology, Tri-Service General Hospital, National Defense Medical Center
Taipei, Taiwan
Introduction:
Subjective memory complaints (SMCs) in early to middle adulthood may represent an early indicator of cognitive decline, despite normal performance on objective cognitive assessments.[1] These individuals face a 4.5-6.5 times higher risk of developing Alzheimer's disease or mild cognitive impairment, making SMCs a crucial presymptomatic stage in the AD continuum.[2, 3] Neuroimaging studies have shown that individuals with SMCs exhibit functional alterations in brain connectivity, particularly in regions commonly affected by AD. However, most studies have focused on populations aged >60 years, while emerging evidence suggests examining younger populations may reveal early pathological changes preceding clinically observable cognitive impairment.[4, 5]Additionally, the heterogeneous nature of SMCs and reliance on cross-sectional data have limited our understanding of how network disruptions evolve. Using both cross-sectional and longitudinal approaches with network contingency analysis, which offers enhanced sensitivity to system-level alterations, we aimed to identify early functional connectivity alterations in large-scale brain networks among young to middle-aged adults with SMCs, potentially enabling timely interventions to modify disease progression.
Methods:
We conducted cross-sectional (96 controls, 92 SMCs) and longitudinal (15 controls, 11 SMCs; mean follow-up 4.0±1.4 years) analyses using resting-state functional MRI (rs-fMRI). Participants with SMCs were included based on the Cognitive Change Index (total score ≥16) and normal cognitive performance (MMSE ≥26). All rs-fMRI data underwent standard preprocessing procedures. For network analysis, we constructed large-scale functional connectomes using 260 distinct regions[6-8] organized into nine large-scale networks. Network contingency analysis was employed to detect system-level alterations through three steps: (1) edge-wise ANCOVA to identify connectivity differences between groups while controlling for age, sex, education, and depression scores; (2) partitioning of significant edges into network-pair blocks; and (3) determination of network-level significance through permutation testing (10,000 iterations, FDR-corrected q<0.05). For longitudinal analysis, we quantified within-subject annualized changes in edge-wise functional connectivity between time points and applied the same network-level statistical framework. Additionally, receiver operating characteristic curves were constructed using mean sub-block connectivity measures to evaluate their diagnostic utility in distinguishing SMCs from controls, and logistic regression was used to generate combined risk probability scores.(fig. 1)
Results:
The cross-sectional analysis revealed significantly reduced connectivity within the default mode network (DMN) and between sensorimotor and cerebellar networks in individuals with SMCs (pFDR<0.05) (fig.2). Longitudinal investigation demonstrated progressive increases in limbic connectivity with both the frontoparietal network and DMN over the 4-year follow-up period, suggesting an early compensatory mechanism. These adaptive changes may indicate neural resilience attempts despite developing network inefficiencies. Combining altered DMN-DMN and sensorimotor-cerebellar connectivity patterns for discriminating individuals with SMCs from controls yielded an area under the curve of 0.749 (95% CI: 0.680-0.817), indicating potential diagnostic utility.
Conclusions:
Using network contingency analysis, we identified subtle but significant network disruptions in early-stage SMCs, particularly involving DMN, sensorimotor, cerebellar, and limbic networks. Progressive enhancement of limbic connectivity may represent a compensatory mechanism preceding cognitive decline. These findings suggest potential neuroimaging biomarkers for early identification and monitoring of cognitive decline risk, highlighting the importance of investigating network alterations in younger populations with SMCs.
Learning and Memory:
Implicit Memory
Lifespan Development:
Aging 2
Modeling and Analysis Methods:
fMRI Connectivity and Network Modeling 1
Keywords:
Aging
FUNCTIONAL MRI
Memory
MRI
Other - default mode network
1|2Indicates the priority used for review
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