Gamma Sensory Stimulation Preserves Corpus Callosum, P-Tau 217 and 181 Correlate With Clinical Outcomes, Lecanemab ARIA Risk Highest in Elevated Aß42/Total Tau Ratios

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Welcome to this special edition of Neurology News Network. I'm Marco Meglio. This week’s episode is centered around the AD/PD International Conference on Alzheimer’s and Parkinson’s Disease.

Cognito Therapeutics presented a pair of posters highlighting its gamma sensory stimulation device in patients with Alzheimer disease. In these data, findings showed that sensory stimulation delivered by Spectris effectively evoked 40 Hz steady-state oscillation, and led to preserved corpus callosum (CC) area structure when compared with matched participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). The first analysis compared total and regional CC changes in patients from the previously conducted OVERTURE study (NCT03556280) to a matched ADNI cohort. To ensure baseline comparability with ADNI controls, OVERTURE participants with Mini-Mental State Examination (MMSE) scores of 21-26 were selected. After 6 months of treatment with Spectris, a non-invasive neuromodulation device, patients demonstrated significant preservation of the total CC area and its subregions (genu/rostrum, anterior body, mid body, posterior body, splenium). Overall, the difference in percentage change in total CC area between active and sham groups were 2.28 (±0.87; P <.02).

Using recent trials of anti-amyloid antibodies for Alzheimer disease (AD), investigators found that changes on phosphorylated tau (p-Tau)217 and p-Tau181 correlated well with clinical end points like Clinical Dementia Rating-sum of boxes (CDR-SB). Overall, the data highlight these biomarker’s ability to predict clinical outcome in a clinical trial setting. Presented at the 2025 AD/PD International Conference on Alzheimer’s and Parkinson’s Diseases, held April 1-5 in Vienna, Austria, study authors looked at the ENGAGE and EMERGE trials of aducanumab (Aduhelm; Biogen), the TRAILBLAZER studies of donenamab (Kisulna; Eli Lilly), and the Clarity AD trial of lecanemab (Leqembi; Eisai). Led by Craig Mallinckrodt, PhD, a consultant at Pentara Corporation, the study looked at both patient-level and group-level correlations between biomarkers and clinical outcomes, using Cohen’s d effect size for standardization and weighted Pearson correlation to assess group-level associations.

Findings from a single-center retrospective study revealed that higher amyloid-ß (Aß)42/total tau index (ATI) ratios in cerebrospinal fluid (CSF) leads to an increased risk of amyloid-imaging abnormalities (ARIA) in lecanemab-treated patients with early-stage Alzheimer disease (AD). Overall, these data suggest ATI may serve as a candidate CSF biomarker for predicting ARIA risk, potentially enhancing patient selection and monitoring during therapy. The trial, led by Javier Romero, MD, director of the R.H Ackerman Neurovascular Lab at Massachusetts General Hospital, featured 54 patients with AD treated with lecanemab, 27 of whom developed ARIA post-treatment. Coming into the study, the baseline characteristics were comparable between ARIA-positive and ARIA-negative patients; however, over time, investigators observed that ATI was significantly higher among patients who developed ARIA (0.8760 vs 0.6217; P = .0337). These findings were confirmed on logistic regression, as higher ATI was correlated with increased ARIA risk (OR, 8.741; 95% CI, 1.242-92.19; P = .0284), with an area under the receiver operating curve of 0.696 (P = .042).

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