Relationship Between General Cognition, Visual Assessed Cortical Atrophy, and Cerebrospinal Fluid Biomarkers in Alzheimer’s Disease: A Cross-Sectional Study from a Chinese PUMCH Cohort

Abstract

Background: Cerebrospinal fluid (CSF) biomarkers are widely accepted as manifestations of Alzheimer’s disease (AD) pathogenesis and incorporated into biological definition of AD. However, the correlations between CSF and other biomarkers such as neuroimaging and neuropsychiatric evaluation are complicated and inconsistent. Objective: We aimed to better interpreting CSF biomarkers results accompanying with other indexes in improving accurate diagnosis of AD. Methods: 112 AD patients and 30 cognitive normal controls were selected. Commercial accessible ELISA kits were introduced for measurement of CSF t-tau, p-tau181, Aβ 1–42, and NfL based on standard protocol. MRI examinations were performed using a 3-T MRI scanner and visual rating scales including medial temporal atrophy score and Koedam’s scale were used to evaluate medial temporal atrophy and posterior region atrophy. Results: CSF biomarkers’ profile including decreased concentration of Aβ 1–42, increased concentration of t-tau, p-tau181, t-tau/Aβ 1–42, and NfL were diagnostic between AD and control. CSF biomarkers profile was not influenced by the APOE genotype. Increased concentration of t-tau and NfL, as well as ratio of t-tau/Aβ 1–42 were related to decrease of Mini-Mental State Examination (MMSE) score while concentration of Aβ 1–42 not. Visual assessed cortical atrophy was related to MMSE score, but most of the CSF biomarkers were not related to atrophy, except that increased concentration of p-tau181 was significantly associated with atrophy of posterior cortical region. Conclusion: Our results supported CSF biomarkers were helpful in diagnosis of AD. However, CSF biomarkers were cross-sectional reflection of pathogenesis, which did not correlate well with clinical progression. CSF biomarkers should be interpreted in combination with MRI and cognitive evaluation in clinical use.

Associations of multiple visual rating scales based on structural magnetic resonance imaging with disease severity and cerebrospinal fluid biomarkers in patients with Alzheimer’s disease

“…In addition, a significant association was found between the lower concentrations of Aβ 1−42 and WMLs in our study, which might imply a link between white matter macrostructural and amyloid pathology microstructural damage (Pietroboni et al, 2018). Although PA was found to be associated with an increased concentration of p-tau181 in AD in previous studies (Lehmann et al, 2013;Mao et al, 2021), we did not find any association between CSF tau and brain atrophy possibly because CSF tau was a biomarker of global neurodegeneration, whereas visual rating scales were markers of local neurodegeneration (Abdelnour et al, 2020). Furthermore, the employment of multiple visual rating scales to correlate the CSF core biomarkers with different regional brain atrophy might be a useful predictive tool for clinicians to use in clinical practice.…”

“…Some previous studies used visual rating scales to build a model for predicting and diagnosing AD, identifying patients with AD from normal aging (Sheng et al, 2020), or distinguishing early-and late-onset AD (Yuan et al, 2019;Park et al, 2021;Silhan et al, 2021). Mao et al (2021) reported that MTA was positively correlated with the age of patients with AD, rather than PA in a cohort of 112 AD patients; however, they did not report a correlation between visual rating scales and disease severity. There are no studies yet conducted to identify which of these scales have a significant advantage in detecting onset age and disease duration and which can be the best predictor of AD severity.…”

Neurofilaments Light Chain in Neurodegenerative Dementias: A Review of Imaging Correlates

“…Alcolea and colleagues [ 55 ] reported a negative association between CSF NfLs and cortical thickness in the left lateral temporal lobe in 33 AD patients. Conversely, a larger study on 112 AD patients with positive CSF biomarkers failed to find a significant association between CSF NfLs and MTA and posterior atrophy scores [ 41 ].…”

A combination model of AD biomarkers revealed by machine learning precisely predicts Alzheimer's dementia: China Aging and Neurodegenerative Initiative (CANDI) study

“…3 Indeed, some research groups have investigated these biomarkers in Chinese cohorts and discovered important clues for AD diagnosing. [4][5][6][7] However, little research effort has been made to undertake a comprehensive study based on the A/T/N framework in China, and it remains unclear whether biomarkers could reflect the brain pathologies within the Chinese population.…”

“…The A/T/N framework consists of seven major AD biomarkers, which are further divided into three binary categories: “A,” amyloid beta (Aβ) deposition (Aβ positron emission tomography [PET], cerebrospinal fluid [CSF] Aβ42/ Aβ40, or low CSF Aβ42 level); “T,” aggregated tau (tau PET or CSF phosphorylated tau [p‐tau]), and “N,” neurodegeneration or neuronal injury ([18F]‐fluorodeoxyglucose [FDG]–PET, structural magnetic resonance imaging [MRI], or CSF total tau [t‐tau]) 3 . Indeed, some research groups have investigated these biomarkers in Chinese cohorts and discovered important clues for AD diagnosing 4‐7 . However, little research effort has been made to undertake a comprehensive study based on the A/T/N framework in China, and it remains unclear whether biomarkers could reflect the brain pathologies within the Chinese population.…”