Alberto Mario Chiarandon

Alzheimer’s disease (AD) is the most common cause of neurocognitive disorder, and the integration of cognitive assessment with biological markers remains essential for clinical characterization. The Clock Drawing Test (CDT) is a brief and widely used screening tool assessing visuospatial and executive functions, which may reflect underlying neurodegenerative processes. This study investigated the diagnostic performance of the CDT and its association with cerebrospinal fluid (CSF) biomarkers within the A/T/(N) research framework. Ninety-seven patients with mild or major neurocognitive disorder were classified as AD or non-AD according to CSF amyloid-β, phosphorylated tau, and total tau profiles, and compared with 36 healthy participants. All subjects underwent a comprehensive neuropsychological evaluation, including the CDT scored using the quantitative–qualitative method proposed by Rouleau et al. Group comparisons, ROC analyses, and regression models adjusted for age, sex, and education were performed. CDT scores effectively distinguished patients from healthy participants, showing large effect sizes, and modestly differentiated AD from non-AD profiles, particularly on the Hands subscale. Diagnostic accuracy was fair, with adjusted AUC values ranging from 0.65 to 0.75. Lower CDT performance was significantly associated with higher CSF total tau levels, while associations with amyloid-β and phosphorylated tau were not robust after correction. These findings suggest that the CDT is sensitive to cognitive impairment severity and shows limited but meaningful relationships with neurodegenerative biomarkers, supporting its role as a practical complementary tool alongside biological assessment.

Background: Frailty is a multidimensional syndrome reflecting reduced physiological reserve, increasingly recognized as a relevant factor in the clinical assessment of older adults with cognitive disorders. Objective: To explore the association between frailty, as measured by the Multidimensional Prognostic Index (MPI), cognitive performance, and plasma biomarkers of Alzheimer’s disease (AD), and to examine the correlation between plasma and cerebrospinal fluid (CSF) biomarkers. Methods: This cross-sectional observational study included 40 patients (mean age 68.0 ± 9.0 years; 42.5% female) undergoing a diagnostic workup for cognitive decline. Patients were classified into AD (n = 20) and non-AD (n = 20) groups based on CSF AT[N] profiles. Frailty was assessed using the MPI. Linear and logistic regression models adjusted for age, sex, and education examined associations between MPI, cognitive scores, and plasma biomarkers (Aβ42, Aβ42/40, p-tau181, NfL). Correlations between plasma and CSF biomarkers and ROC analyses were also performed. Results: The AD group showed significantly higher plasma p-tau181 levels and MPI scores. MPI was positively associated with plasma p-tau181 levels (β = 4.26, p = 0.009). Plasma p-tau181 correlated strongly with CSF p-tau181 (R = 0.523, p < 0.001) and with CSF Aβ42/40 ratio (R = −0.541, p < 0.001) and showed high diagnostic accuracy (AUC = 0.910). Combining MPI with plasma biomarkers improved classification between AD and non-AD cases (AUC = 0.941). Conclusions: These findings support the value of incorporating frailty assessment in the diagnostic process of AD. The integration of geriatric tools and blood-based biomarkers may improve early detection and promote a more comprehensive approach in dementia evaluation.

Background: Neurofilament light chain (NfL) is a promising biomarker of neuroaxonal injury, increasingly used to monitor neurodegeneration in Alzheimer’s disease (AD). Multiple analytical platforms are available for NfL quantification in cerebrospinal fluid (CSF), but data on cross-platform consistency remain limited. Objective: This pilot study aimed to provide CSF NfL concentrations measured using Simoa and Lumipulse immunoassays in patients with biologically confirmed AD. Methods: Twenty-eight patients with cognitive impairment fulfilling the biological criteria for AD were enrolled. CSF NfL levels were measured using both Simoa and Lumipulse immunoassays. Statistical analyses assessed intra-individual agreement, correlation between platforms, and associations with cognitive status. Results: NfL concentrations measured with Simoa and Lumipulse showed a strong positive correlation between platforms (Spearman’s ρ = 0.965, p < 0.001), demonstrating excellent analytical concordance. Conclusions: In this pilot study, Simoa and Lumipulse yielded strongly correlated CSF NfL measurements, providing initial evidence of cross-platform consistency. However, these findings require confirmation in larger and diverse cohorts before definitive validation.