Dynamic changes in cognition and brain function over a five-year follow-up after COVID-19 recovery: a longitudinal fMRI study
Abstract
Background: Long-term trajectories of brain function and cognition after COVID-19 remain unclear beyond early recovery.
Methods: We conducted a single-center longitudinal study of 14 hospitalized COVID-19 survivors assessed at 1 (V1), 2 (V2), and 5 (V5) years post-recovery, alongside 20 healthy controls (HCs). Participants underwent resting-state fMRI and neuropsychological assessments. The imaging indices analyzed included ALFF, ReHo, and small-worldness.
Results: Compared to HCs, survivors at V5 exhibited poorer sleep and cognitive performance, as reflected by higher Pittsburgh Sleep Quality Index (PSQI) scores and lower Logical Memory (LM) and backward Digit Span (BDS) scores. Compared to HCs, survivors at V5 also showed increased ALFF in the right supramarginal gyrus (SMG.R), decreased ALFF in the right precuneus, and decreased ReHo in the left middle frontal gyrus—all of which were significantly associated with reduced cognitive function and poor sleep quality. Longitudinally, PSQI scores decreased from V1 to V2; 36‑Item Short‑Form Health Survey physical functioning (SF‑PF) scores increased from V1 to V2; and SF‑Vitality (VT) scores increased at V2 relative to both V1 and V5. For neural dynamics, ALFF decreased in the right precentral gyrus at V2 (vs. that at V1), but increased in the SMG.R at V5 (vs. that at V2). Additionally, small‑worldness (σ) decreased at V2 and subsequently increased at V5. Notably, this σ value at V5 correlated negatively with BDS scores. All reported findings remained statistically significant (all corrected P < 0.05).
Conclusions: Five years after recovery, survivors exhibited persistent cognitive impairment, sleep disturbances, and functional brain alterations, providing neuroimaging evidence for the long-term neuropsychiatric sequelae of COVID-19.
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BibTeX
@article{yang2026dynamic,
title = {{Dynamic changes in cognition and brain function over a five-year follow-up after COVID-19 recovery: a longitudinal fMRI study}},
author = {Jun-Jie Yang and Shi-Rui Cao and Xiang-Lin Zhou and Si-Hong Huang and Jia-Qi Yao and Li-Jie Zhang and Xin-Jia Xu and Yu-Le Zeng and Xiao Lin and Bei Huang and Jing-Hang Wang and Dan-Hui Yang and Jun Liu},
journal = {BMC Medicine},
year = {2026},
month = nov,
doi = {10.1186/s12916-026-05379-6},
url = {https://link.springer.com/article/10.1186/s12916-026-05379-6},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Dynamic changes in cognition and brain function over a five-year follow-up after COVID-19 recovery: a longitudinal fMRI study
AU - Jun-Jie Yang
AU - Shi-Rui Cao
AU - Xiang-Lin Zhou
AU - Si-Hong Huang
AU - Jia-Qi Yao
AU - Li-Jie Zhang
AU - Xin-Jia Xu
AU - Yu-Le Zeng
AU - Xiao Lin
AU - Bei Huang
AU - Jing-Hang Wang
AU - Dan-Hui Yang
AU - Jun Liu
PY - 2026
DA - 2026/11/06
JO - BMC Medicine
DO - 10.1186/s12916-026-05379-6
UR - https://link.springer.com/article/10.1186/s12916-026-05379-6
AB - Background: Long-term trajectories of brain function and cognition after COVID-19 remain unclear beyond early recovery. Methods: We conducted a single-center longitudinal study of 14 hospitalized COVID-19 survivors assessed at 1 (V1), 2 (V2), and 5 (V5) years post-recovery, alongside 20 healthy controls (HCs). Participants underwent resting-state fMRI and neuropsychological assessments. The imaging indices analyzed included ALFF, ReHo, and small-worldness. Results: Compared to HCs, survivors at V5 exhibited poorer sleep and cognitive performance, as reflected by higher Pittsburgh Sleep Quality Index (PSQI) scores and lower Logical Memory (LM) and backward Digit Span (BDS) scores. Compared to HCs, survivors at V5 also showed increased ALFF in the right supramarginal gyrus (SMG.R), decreased ALFF in the right precuneus, and decreased ReHo in the left middle frontal gyrus—all of which were significantly associated with reduced cognitive function and poor sleep quality. Longitudinally, PSQI scores decreased from V1 to V2; 36‑Item Short‑Form Health Survey physical functioning (SF‑PF) scores increased from V1 to V2; and SF‑Vitality (VT) scores increased at V2 relative to both V1 and V5. For neural dynamics, ALFF decreased in the right precentral gyrus at V2 (vs. that at V1), but increased in the SMG.R at V5 (vs. that at V2). Additionally, small‑worldness (σ) decreased at V2 and subsequently increased at V5. Notably, this σ value at V5 correlated negatively with BDS scores. All reported findings remained statistically significant (all corrected P < 0.05). Conclusions: Five years after recovery, survivors exhibited persistent cognitive impairment, sleep disturbances, and functional brain alterations, providing neuroimaging evidence for the long-term neuropsychiatric sequelae of COVID-19.
SN - 1741-7015
ER -