Nexalin's Item-Level ADAS-Cog Analysis Reveals Domain-Specific Cognitive Gains in Alzheimer's Trial
核心洞察
Nexalin Technology (搜索) reported an exploratory, item-level analysis of ADAS-Cog data from its 46-patient randomized, sham-controlled trial of the Gen-2 SYNC DIFS (搜索) device in mild Alzheimer's disease (搜索).
Among 20 active-arm participants with complete data, 10 achieved a clinically meaningful improvement of four or more points, with the largest gains (eight points) seen in the most cognitively impaired patients at baseline.
Domain-level improvements in recognition memory, language comprehension, spoken language, word-finding, and constructional praxis remained evident three months after treatment ended.
Nexalin Technology (搜索), Inc. (Nasdaq: NXL) announced results of an exploratory, item-level analysis of Alzheimer's Disease (搜索) Assessment Scale–Cognitive Subscale (ADAS-Cog) data from its completed randomized, double-blind, sham-controlled clinical trial evaluating the company's proprietary 15 milliamp (mA) Gen-2 SYNC DIFS (搜索) neurostimulation device in patients with mild Alzheimer's disease. The analysis, announced September 3, 2026, identified previously unreported improvements across five Alzheimer's disease-related cognitive domains, with gains still evident three months after treatment concluded.
The underlying 46-patient trial has been published in two peer-reviewed journals: the Journal of Alzheimer's Disease (搜索) (2024) and Radiology (2025). As previously reported, the trial demonstrated statistically significant improvements versus sham on the Mini-Mental State Examination (MMSE) (P = .001) and the Montreal Cognitive Assessment (MoCA) (P = .03), together with treatment-associated enhancements in functional connectivity between the hippocampus and key cortical regions observed on functional MRI.
Domain-Level Findings Beneath the Composite Score
While the original publication focused on predefined primary and secondary endpoints, the additional analysis examined individual cognitive and functional subscales within the validated ADAS-Cog assessment. Because meaningful changes within individual cognitive domains can be diluted when combined into a single composite figure, the company conducted a descriptive, item-level analysis of individual participant data from the active treatment arm to better understand which specific domains responded to treatment, and in which patients.
Among the 20 active-arm participants with complete assessment data, 10 achieved an improvement of four or more points at one or more assessment points — a threshold widely regarded as clinically meaningful on the ADAS-Cog. The largest individual improvements, of eight points each, were observed in the two participants with the greatest cognitive impairment at baseline, suggesting a potential relationship between baseline disease severity and treatment response.
Domain-level review identified improvement patterns concentrated in recognition memory, comprehension of spoken language, spoken language ability, word-finding, and constructional praxis at the three-month follow-up assessment — three months after the final treatment session.
Guiding the Next Stage of Development
The analysis was conducted to guide endpoint selection and patient-selection strategy for the company's planned U.S. pilot study in Alzheimer's disease (搜索). "The value of this work is that it tells us where to look next," said Mark White, Chief Executive Officer of Nexalin Technology (搜索). "Our published trial demonstrated significant improvements versus sham on the MMSE and MoCA, with corresponding changes on brain imaging. The item-level ADAS-Cog analysis now gives us a more granular map of the cognitive domains in which responses were concentrated — and which patients responded most — and we expect these insights will directly shape endpoint selection and patient-selection strategy as we advance our planned U.S. pilot study with the FDA."
Dr. David Owens, Chief Medical Officer of Nexalin Technology (搜索), added: "Composite scales such as the ADAS-Cog are essential tools, but they can obscure domain-specific effects, particularly in smaller studies. Examining the data beneath the composite at the item level is a standard and appropriate way to generate hypotheses for the next stage of clinical development. We expect these observations to help us design a more focused and rigorous study, including how we select patients and define endpoints."
The company expects to incorporate these findings into the protocol design for its planned U.S. pilot study of the Gen-2 SYNC console in Alzheimer's disease (搜索), building on feedback received in its Q-Submission meeting with the FDA, announced December 3, 2025, and the broader FDA strategy outlined in the company's April 15, 2026 announcement.
Study Limitations
The subscale analysis was post-hoc, exploratory, and descriptive in nature. It was not prespecified in the trial protocol, includes a small number of participants, and has not been adjusted for multiple comparisons. Findings from analyses of this kind are hypothesis-generating rather than evidence of treatment efficacy and are intended to inform the design of future controlled clinical studies.
The company noted that the responder and domain-level observations were derived from active-arm participants only and without a corresponding sham-arm comparison, and therefore may not be attributable to treatment. Nexalin intends to provide further updates as its U.S. Alzheimer's program advances.