Macroscale Cortical Hierarchy and Spontaneous Speech for Preclinical Alzheimer’s Disease: A Narrative Review Focused on Remote Screening and Longitudinal Prognosis — Oak Academic Publishing
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Macroscale Cortical Hierarchy and Spontaneous Speech for Preclinical Alzheimer’s Disease: A Narrative Review Focused on Remote Screening and Longitudinal Prognosis
Cerebrovascular Diseases Department, Zhuhai Clinical Medical College of Jinan University (Zhuhai People’s Hospital, The Affiliated Hospital of Beijing Institute of Technology), Zhuhai, China
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Cerebrovascular Diseases Department, Zhuhai Clinical Medical College of Jinan University (Zhuhai People’s Hospital, The Affiliated Hospital of Beijing Institute of Technology), Zhuhai, China
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Cerebrovascular Diseases Department, Zhuhai Clinical Medical College of Jinan University (Zhuhai People’s Hospital, The Affiliated Hospital of Beijing Institute of Technology), Zhuhai, China
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Cerebrovascular Diseases Department, Zhuhai Clinical Medical College of Jinan University (Zhuhai People’s Hospital, The Affiliated Hospital of Beijing Institute of Technology), Zhuhai, China
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Cerebrovascular Diseases Department, Zhuhai Clinical Medical College of Jinan University (Zhuhai People’s Hospital, The Affiliated Hospital of Beijing Institute of Technology), Zhuhai, China
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Cerebrovascular Diseases Department, Zhuhai Clinical Medical College of Jinan University (Zhuhai People’s Hospital, The Affiliated Hospital of Beijing Institute of Technology), Zhuhai, China
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Cerebrovascular Diseases Department, Zhuhai Clinical Medical College of Jinan University (Zhuhai People’s Hospital, The Affiliated Hospital of Beijing Institute of Technology), Zhuhai, China
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Cerebrovascular Diseases Department, Zhuhai Clinical Medical College of Jinan University (Zhuhai People’s Hospital, The Affiliated Hospital of Beijing Institute of Technology), Zhuhai, China
,
Cerebrovascular Diseases Department, Zhuhai Clinical Medical College of Jinan University (Zhuhai People’s Hospital, The Affiliated Hospital of Beijing Institute of Technology), Zhuhai, China
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Cerebrovascular Diseases Department, Zhuhai Clinical Medical College of Jinan University (Zhuhai People’s Hospital, The Affiliated Hospital of Beijing Institute of Technology), Zhuhai, China
1 Cerebrovascular Diseases Department, Zhuhai Clinical Medical College of Jinan University (Zhuhai People’s Hospital, The Affiliated Hospital of Beijing Institute of Technology), Zhuhai, China
2 Cerebrovascular Diseases Department, Zhuhai Clinical Medical College of Jinan University (Zhuhai People’s Hospital, The Affiliated Hospital of Beijing Institute of Technology), Zhuhai, China
3 Cerebrovascular Diseases Department, Zhuhai Clinical Medical College of Jinan University (Zhuhai People’s Hospital, The Affiliated Hospital of Beijing Institute of Technology), Zhuhai, China
4 Cerebrovascular Diseases Department, Zhuhai Clinical Medical College of Jinan University (Zhuhai People’s Hospital, The Affiliated Hospital of Beijing Institute of Technology), Zhuhai, China
5 Cerebrovascular Diseases Department, Zhuhai Clinical Medical College of Jinan University (Zhuhai People’s Hospital, The Affiliated Hospital of Beijing Institute of Technology), Zhuhai, China
6 Cerebrovascular Diseases Department, Zhuhai Clinical Medical College of Jinan University (Zhuhai People’s Hospital, The Affiliated Hospital of Beijing Institute of Technology), Zhuhai, China
7 Cerebrovascular Diseases Department, Zhuhai Clinical Medical College of Jinan University (Zhuhai People’s Hospital, The Affiliated Hospital of Beijing Institute of Technology), Zhuhai, China
8 Cerebrovascular Diseases Department, Zhuhai Clinical Medical College of Jinan University (Zhuhai People’s Hospital, The Affiliated Hospital of Beijing Institute of Technology), Zhuhai, China
9 Cerebrovascular Diseases Department, Zhuhai Clinical Medical College of Jinan University (Zhuhai People’s Hospital, The Affiliated Hospital of Beijing Institute of Technology), Zhuhai, China
10 Cerebrovascular Diseases Department, Zhuhai Clinical Medical College of Jinan University (Zhuhai People’s Hospital, The Affiliated Hospital of Beijing Institute of Technology), Zhuhai, China
Amyloid- β (A β ) pathology can be detected years before clinical Alzheimer’s disease (AD), yet forecasting who will decline—and how rapidly—remains difficult in cognitively unimpaired (CU) and subjective cognitive decline (SCD) populations. Resting-state fMRI connectome gradients provide a low-dimensional description of macroscale cortical hierarchy, typically spanning unimodal systems to transmodal association cortex anchored in the default mode network (DMN). Alterations in gradient range, dispersion, and template similarity have been reported across the AD continuum and are increasingly described in preclinical A β + cohorts. In parallel, spontaneous speech has emerged as a scalable digital phenotype: acoustic timing and pausing can be captured remotely and repeatedly, extracted automatically without manual transcription, and tracked longitudinally with minimal practice effects. This narrative review synthesizes: 1) why gradient-based hierarchy metrics are biologically plausible early functional readouts of preclinical AD, 2) the emerging evidence for atypical hierarchy in CU/SCD A β + individuals, 3) the speech feature families most suitable for scalable early detection and prognosis—emphasizing timing/pause measures—and 4) practical standards for longitudinal models predicting cognitive decline slope and conversion to mild cognitive impairment (MCI). We conclude that gradients and speech—especially transcription-free timing markers—are complementary and potentially synergistic, but translation requires rigorous confound control (motion, hearing, affect, device variability), transparent reporting, calibration, and external validation.
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