Higher admission homocysteine was associated with discharge-phase neurocognitive dysfunction, supporting prospective evaluation of homocysteine as a potential marker of short-term neurocognitive vulnerability rather than a validated predictor of persistent post-stroke cognitive impairment.
Key Findings
Results
Discharge neurocognitive dysfunction was present in 43.2% of patients admitted for acute cerebrovascular disease in a high-altitude setting.
98 of 227 patients (43.2%) had discharge neurocognitive dysfunction
The cohort included adults admitted for acute ischemic stroke, intracerebral hemorrhage, or transient ischemic attack
Neurocognitive dysfunction was documented within 24-48 h before discharge and adjudicated independently by two reviewers blinded to homocysteine levels
Standardized cognitive instruments were not systematically available for adjudication
Results
Admission serum homocysteine levels were significantly higher in patients who developed discharge neurocognitive dysfunction compared to those who did not.
Mean homocysteine was 18.3 ± 6.2 µmol/L in patients with dysfunction versus 12.4 ± 4.7 µmol/L in those without dysfunction
P < 0.001 for the between-group difference
Homocysteine was measured from the first available serum sample within 24 h of hospital arrival
Results
Prevalence of discharge neurocognitive dysfunction increased monotonically across homocysteine tertiles.
Dysfunction prevalence was 22.4% in the lowest tertile (T1), 38.5% in the middle tertile (T2), and 69.9% in the highest tertile (T3)
P for trend < 0.001 across tertiles
Results
Each 1 µmol/L increase in admission homocysteine was independently associated with higher odds of discharge neurocognitive dysfunction in the fully adjusted model.
OR 1.14 (95% CI 1.07–1.21, P < 0.001) per 1 µmol/L increase in homocysteine
The model was sequentially adjusted for demographic, renal, neurological, neuroimaging, and cerebrovascular phenotype-related factors
This was the primary fully adjusted logistic regression model
Results
The highest homocysteine tertile (T3) was associated with over four-fold higher odds of discharge neurocognitive dysfunction compared to the lowest tertile (T1) in the fully adjusted model.
OR 4.36 (95% CI 2.00–9.51, P < 0.001) for T3 versus T1
This association persisted after full covariate adjustment
Results
The association between admission homocysteine and discharge neurocognitive dysfunction was consistent across prespecified sensitivity analyses.
Sensitivity analyses included exclusion of patients with delirium or positive CAM-ICU screening
Analyses were also restricted to the acute ischemic stroke subgroup
Estimates were described as 'similar' to the primary model across these analyses
Methods
The study was conducted in a single-center high-altitude clinical setting using a retrospective cohort design.
Total sample size was 227 adults
The study was retrospective and single-center
The high-altitude setting was explicitly identified as a contextual feature of the study
Logistic regression was the primary analytic method, with sequential adjustment across multiple covariate domains
What This Means
This research examined whether a blood marker called homocysteine, measured shortly after hospital admission, was linked to thinking and memory problems (neurocognitive dysfunction) that patients experienced near the time of discharge after a stroke or related brain event. The study looked at 227 patients at a hospital located at high altitude, and found that nearly half (43.2%) had neurocognitive dysfunction at discharge. Patients who had these cognitive problems had notably higher homocysteine levels on admission—about 18 µmol/L on average compared to about 12 µmol/L in those without problems. Even after accounting for many other factors like age, kidney function, and stroke severity, higher homocysteine remained strongly associated with cognitive dysfunction at discharge, with patients in the highest homocysteine group being over four times more likely to have dysfunction than those in the lowest group.
This matters because cognitive problems at the time of discharge can interfere with a patient's ability to participate in rehabilitation, manage their own care safely, and follow medical instructions after leaving the hospital. Homocysteine is a routine, inexpensive blood test that is already commonly measured in clinical practice, meaning it could potentially serve as an early signal to identify patients who may need additional cognitive support before and after discharge. However, the researchers were careful to note that this was a retrospective, single-center study without standardized cognitive testing tools, so homocysteine should be considered a potential marker of short-term cognitive vulnerability rather than a proven predictor of long-term cognitive decline after stroke. Prospective studies with formal cognitive assessments are needed to confirm these findings.
Wang N, Sun J, Ji W. (2026). Association of Admission Serum Homocysteine with Discharge Neurocognitive Dysfunction after Acute Cerebrovascular Disease in a High-Altitude Setting.. Journal of visualized experiments : JoVE. https://doi.org/10.3791/73407