Cognitive impairment of cerebral small vessel disease (CSVD) is one of the most common cognitive disorders. It has a high incidence and results in heavy social burden; thus, it is essential to provide reasonable diagnosis and treatment in clinical practice. Based on the results of clinical research and related reports, combined with the actual situation in China, we propose a diagnosis and treatment guideline for cognitive impairment of CSVD.

Background: Several blood-based biomarkers are promising to be used in the diagnosis of Alzheimer’s disease (AD) including Aβ42/40, p-tau181, and neurofilament light (NfL). The kidney is associated with the clearance of proteins. It is crucial to evaluate the effect of renal function on the diagnostic performance of these biomarkers before clinical implementation, which is important for the establishment of reference ranges and the interpretation of results.Methods: This study is a cross-sectional analysis based on ADNI cohort. Renal function was determined by the estimated glomerular filtration rate (eGFR). Plasma Aβ42/40 was measured by liquid chromatography–tandem mass spectrometry (LC–MS/MS). Plasma p-tau181 and NfL were analyzed by Single Molecule array (Simoa) technique. [18F] florbetapir-PET (Aβ-PET) was used as a reference standard to estimate the brain amyloid load. The cutoff of Aβ-PET positivity was defined as ≥1.11. Linear regression models were used to investigate the associations of continuous eGFR with each plasma biomarker separately. The diagnostic accuracies of plasma biomarkers for positive brain amyloid across different renal function groups were analyzed by Receiver operating characteristic (ROC) curve. Youden-Index was used to determine the cutoff levels.Results: A total of 645 participants were included in this study. The levels and diagnostic performance of Aβ42/40 were not affected by renal function. eGFR was only found negatively associated with p-tau181 levels in Aβ-PET negetive sample (β = −0.09, p = 0.039). eGFR was found negatively associated with NfL levels both in whole sample and Aβ-PET stratified groups (β = −0.27, p < 0.001 in whole sample; β = −0.28, p = 0.004 in A⁻; β = −0.27, p < 0.001 in A⁺). The diagnostic accuracies of p-tau181 and NfL were not affected by renal function. But the cutoff values of p-tau181 and NfL changed in participants with mild to moderate eGFR decline compared to participants with normal eGFR.Conclusion: Plasma Aβ42/40 was a robust biomarker for AD which was not affected by renal function. Plasma p-tau181 and NfL levels were affected by renal function, specific reference values of them should be considered in populations with different renal function stages.

INTRODUCTION: Sleep disturbances are associated with Alzheimer's disease (AD) and Alzheimer's disease and related dementias (ADRD), but the relationship between sleep architecture, particularly rapid eye movement (REM) sleep, and AD/ADRD biomarkers remains unclear. METHODS: We enrolled 128 adults (64 with Alzheimer's disease, 41 with mild cognitive impairment [MCI], and 23 with normal cognition [NC]), mean age 70.8 ± 9.6 years, 56.9% female, from a tertiary hospital in China. Participants underwent overnight polysomnography (PSG), amyloid β (Aβ) positron emission tomography (PET), and plasma biomarker analysis: phosphorylated tau at threonine 181 (p‐tau181), neurofilament light (NfL), and brain‐derived neurotrophic factor (BDNF). RESULTS: After adjusting for demographics, apolipoprotein E ( APOE ) ε4 status, cognition, and comorbidities, the highest tertile of REM latency was associated with higher Aβ burden ( β = 0.08, 95% confidence interval [CI]: 0.03 to 0.13, p = 0.002), elevated p‐tau181 ( β = 0.19, 95% CI: 0.02 to 0.13, p = 0.002), and reduced BDNF levels ( β = ‐0.47, 95% CI: –0.68 to –0.13, p = 0.013), compared to the lowest tertile. DISCUSSION: Prolonged REM latency may serve as a novel marker or risk factor for AD/ADRD pathogenesis. Highlights: Rapid eye movement latency (REML) may be a potential marker for Alzheimer's disease and Alzheimer's disease and related dementias (AD/ADRD) pathogenesis. Prolonged REML was associated with higher amyloid beta (Aβ) burden, phosphorylated tau‐181 (p‐tau181), and lower brain‐derived neurotrophic factor (BDNF) levels. Intervention trial is needed to determine if targeting REML can modify AD/ADRD risk. Slow‐wave sleep was not associated with AD/ADRD biomarkers.