Addition of Aβ42 to Total Cerebral Small Vessel Disease Score Improves the Prediction for Cognitive Impairment in Cerebral Small Vessel Disease Patients

Abstract

Purpose: To investigate the associations between concentrations of Aβ 40 and Aβ 42 and vascular cognitive impairment (VCI) in cerebral small vessel disease (CSVD) patients and evaluate the value of combination of levels of Aβ 40 or Aβ 42 and the total CSVD score in predicting VCI. Patients and Methods: A total of 199 CSVD patients were divided into VCI group and non-VCI group according to the criteria of VCI. Demographic data, MRI markers of CSVD, blood pressure, vascular risk factors, laboratory markers, and serum Aβ 40 and Aβ 42 concentration were collected. Univariate analysis was performed with the Student's t-test, Mann-Whitney U-test or Chi-square test. Variables with P<0.10 in univariate analysis were then included in multivariate analysis that used a backward stepwise logistic regression model. The predictive values were assessed with receiver operating characteristic (ROC) curve. Results: VCI was determined in 112 CSVD patients (56.3%). Hyperlipidemia (OR: 1.618, 95% CI: 1.265-3.049), the total CSVD score (OR: 1.414, 95% CI: 1.213-2.278) and serum Aβ 42 concentration (OR: 1.401, 95% CI: 1.212-1.946) were independent risk factors for VCI in CSVD patients with adjustment for age, education years, diabetes and fasting blood-glucose (FBG). The area under curves (AUCs) were 0.640 (SE: 0.040, 95% CI: 0.563-0.718), 0.733 (SE: 0.035, 95% CI: 0.664-0.802) and 0.827 (SE: 0.030, 95% CI: 0.768-0.887), respectively, for the total CSVD score, serum Aβ 42 concentration and their combination applied in predicting VCI in CSVD patients. Z test demonstrated that the AUC of combination prediction was significantly higher than individual prediction (0.827 vs 0.640, Z=3.740, P<0.001; 0.827 vs 0.733, Z=2.039, P=0.021). Conclusion: Combination of Aβ 42 and total CSVD score could significantly elevate the predictive value of cognitive impairment in CSVD patients.

The interaction of global small vessel disease burden and Alzheimer's disease pathologies do not change the independent association of amyloid‐beta with hippocampal volume: A longitudinal study on mild cognitive impairment subjects

“…Whereas previous studies only considered the interaction of individual SVD markers alone with Aβ, our study extended the results to global SVD burden, confirming that global SVD*Aβ can predict executive, memory and language decline in MCI subjects. This was in line with a previous study indicating that the combination of Aβ and global SVD burdens could meaningfully predict cognitive impairment (Liu et al, 2021). Nevertheless, that study only conducted a cross‐sectional analysis, while our study included a 4‐year longitudinal analysis, affirming the predictive value of it, and further revealed how these associations changed over time.…”

“…This may explain how SVD and AD pathology interact. A recent study showed that the interaction of Aβ and WMH can affect cognitive function (Saridin et al, 2020), while some other studies (Banerjee et al, 2017;Freeze et al, 2017) (Liu et al, 2021).…”

“…On the other hand, damaged blood vessels could lead to reduced clearance of Aβ, thus making pathological deposition of Aβ more severe; accumulation of Aβ in and around the cerebral vessels may lead to damage to small blood vessels (Liu et al, 2021). This may explain how SVD and AD pathology interact.…”

Mesenchymal Stem Cells Improve Cognitive Impairment and Reduce Aβ Deposition via Promoting AQP4 Polarity and Relieving Neuroinflammation in Rats With Chronic Hypertension-Induced Cerebral Small-Vessel Disease

“…Besides vascular Aβ lesions found in CAA, an association between Aβ and CSVD has been reported in many studies. Liu et al found that serum Aβ42 combined with the CSVD score could predict cognitive impairment in patients with CSVD (Liu et al, 2021 ). An 8-year longitudinal study suggested that Aβ positivity in amyloid PET was an independent predictor of functional disability regardless of the occurrence of stroke in patients with subcortical VCI (Kang et al, 2022 ).…”

Cerebral Small Vessel Disease: Neuroimaging Features, Biochemical Markers, Influencing Factors, Pathological Mechanism and Treatment

“…Common risk factors, such as coagulation abnormalities, impaired vascular EC function, inflammatory reactions, and uremia-related factors, may occur in patients with ischemic stroke and CSVD, and it has an undesirable effect ( 72 ). Furthermore, latest research shows that Aβ-42 combined with the CSVD score can also be used to predict vascular cognitive dysfunction (VCI) in patients with CSVD ( 73 ).…”