Background and Objectives Nusinersen was approved as the first disease-modifying therapy in spinal muscular atrophy (SMA). Our aim was to analyse therapy-related changes in cerebrospinal fluid (CSF) and serum parameters of adult type 2–3 SMA and to correlate biochemical data with motor functional status. Methods Nine adult SMA type 2–3 patients and ten control subjects without neurodegenerative diseases were included in our single-centre study. Cross-sectional analysis of CSF routine parameters, CSF neurofilament light chain, CSF Tau, CSF phospho-Tau and serum creatinine was performed between SMA patients at baseline (T0) and control subjects. The above-mentioned fluid parameters were longitudinally analysed in the SMA cohort after loading dose (T1) and after four maintenance doses (T2, T3, T4, T5). Hammersmith Functional Motor Scale Expanded (HFMSE), Revised Upper Limb Module (RULM) and the 6-minute walking test (6MWT) were used to evaluate motor outcomes. Results Improvements in HFMSE, RULM and 6MWT were observed only after the loading dose of nusinersen. No significant differences in routine CSF parameters and CSF markers of neurodegeneration were found between SMA patients and control subjects. Serum creatinine levels were significantly lower in SMA patients than in control subjects. CSF/serum albumin ratio (Qalb) significantly increased from T0 to each time point, without any further increase after the maintenance doses. Persistent systemic oligoclonal bands (OCBs) were found in five patients from baseline. Three more patients developed persistent systemic OCBs from T1; one patient showed intrathecal OCBSs from baseline to T5. Markers of neurodegeneration did not change during the follow-up and did not correlate with motor scores at baseline and at each timepoint. Serum creatinine levels significantly correlated with HFMSE and RULM at each time point. Conclusions The increase of the Qalb values and the development of systemic OCBs in some SMA patients could be due to repeated lumbar puncture and to the immunogenic effect of nusinersen. On the other hand, the presence of OCBs in serum and/or CSF at baseline should be further investigated. Furthermore, biomarkers of neurodegeneration did not play a prognostic role in our cohort of adult SMA patients.

Background and purpose: The Food and Drug Administration approved two disease‐modifying treatments (DMTs) for Alzheimer's disease (AD), aducanumab and lecanemab, with limited clinical impact but significant biomarker changes. Identifying suitable candidates for these DMTs outside randomized clinical trials (RCTs) remains uncertain.Methods: This cross‐sectional study, conducted in an Italian tertiary centre for cognitive disorders, aimed to evaluate how the RCT eligibility criteria for DMT treatments applies to participants with early AD. The broader Cummings et al. (Journal of Prevention of Alzheimer's Disease, 2021, 2023) criteria and the clinical differences between DMT candidates were also assessed.Results: The study involved 408 participants (mean age 71.1 ± 8.5 years, 48% male) with a clinical diagnosis of mild cognitive impairment (161/408, 39.5%) or mild dementia (247/408, 60.5%). Amongst them, 169 individuals (41%) showed positive AD pathology biomarkers. Eligibility RCT assessment revealed 14 patients eligible for aducanumab (3.43% of 408) and 28 for lecanemab (6.86% of 408). Following Cummings' real‐world criteria, aducanumab eligibility increased to 9.56%, whereas lecanemab eligibility rose to 8.33%. Applying selection criteria to only the amyloid positive (169 out of 408), the selection for DMTs was 8.3% for aducanumab and 16.5% for lecanemab.Conclusion: Amongst subjects diagnosed with mild AD and mild cognitive impairment in a tertiary centre for cognitive disorders, only a small percentage of patients using RCT diagnostic criteria are eligible for DMT. The application of Cummings criteria strongly increased the DMT candidates. Nevertheless, the majority of patients with cognitive disorders have been excluded from DMTs approved so far.