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Published on: April 23, 2021
The relationship between plasma FOXO3 and cognitive impairment and depressive symptoms in cerebral small vessel
Qiqi Sun1, Lei Liu1, Haoran Ma1
1Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao, China.
Insights
Acute-phase plasma FOXO3 levels correlate with early cognitive impairment in cerebral small vessel disease (CSVD) patients. CSVD burden mediates this association, highlighting FOXO3 as a potential biomarker for neurodegeneration.
Area of Science:
- Neurology
- Vascular Biology
- Molecular Medicine
Background:
- Cerebral small vessel disease (CSVD) significantly contributes to cognitive decline, depression, and disability in older adults.
- The transcription factor Forkhead box O3 (FOXO3) is implicated in neurodegenerative and vascular conditions.
Purpose of the Study:
- To investigate the relationship between acute-phase plasma FOXO3 levels and cognitive/depressive symptoms in CSVD patients.
- To explore the role of CSVD burden in mediating the association between FOXO3 and cognitive function.
Main Methods:
- Prospective cohort study with 183 CSVD patients (recent small subcortical infarct) and 150 controls.
- Plasma FOXO3 levels measured via ELISA at acute phase (≤3 days) and day 7.
- Cognitive and depressive symptoms assessed at discharge; brain MRI evaluated CSVD characteristics; mediation analysis performed.
Main Results:
- CSVD patients exhibited significantly higher plasma FOXO3 levels than controls at both acute and day 7 phases (P < 0.001).
- Acute-phase FOXO3 levels were higher in patients with cognitive impairment (AUC=0.747) but not associated with depressive symptoms.
- Total CSVD burden, particularly white matter hyperintensities, mediated 36.96% of the FOXO3-cognitive impairment association.
Conclusions:
- Acute-phase plasma FOXO3 levels are linked to early cognitive impairment in CSVD patients.
- Further longitudinal studies are needed to confirm the long-term prognostic value of FOXO3.
Background And Purpose:
Cerebral small vessel disease (CSVD) is a leading cause of post-stroke cognitive impairment, depression, and disability in older adults. Forkhead box O3 (FOXO3) is a key transcription factor that plays important roles in neurodegenerative and vascular diseases. This study investigated the correlation of acute-phase plasma FOXO3 levels with cognitive and depressive symptoms in CSVD patients.
Methods:
This prospective cohort study recruited 183 patients with recent small subcortical infarct (RSSI) and 150 healthy controls. Plasma FOXO3 levels were measured by enzyme-linked immunosorbent assay at the acute phase (≤3 days) and day 7. Cognitive and depressive symptoms were assessed at discharge. The brain MRI was used to evaluate CSVD imaging characteristics. Mediation analysis assessed the effect of CSVD on the association between FOXO3 and cognitive function.
Results:
Among the participants, 76 (41.53%) had cognitive impairment, and 40 (21.9%) had depressive symptoms. Plasma FOXO3 levels were profoundly higher in patients at both the acute phase (≤3 days) and day 7 compared with controls (both P < 0.001), with higher levels observed in the acute phase than at day 7 (P < 0.001). Acute-phase plasma FOXO3 was higher in patients with cognitive impairment than in those without (P < 0.001), showing a predictive area under the curve of 0.747. After adjustment, FOXO3 remained unassociated with depressive symptoms (P = 0.232). Total CSVD burden was associated with cognitive impairment (odds ratio: 1.728, 95%CI 1.084-2.756, P = 0.022). Mediation analysis showed that total CSVD burden, prominently white matter hyperintensities, mediated 36.96% of the association between FOXO3 and cognitive impairment.
Conclusions:
Acute-phase FOXO3 levels are associated with early cognitive impairment at discharge, whereas its long-term prognostic value requires validation in future longitudinal follow-up studies.
