Slowing Progression With Zervimesine in Dementia With Lewy Bodies

Tony Caggiano, MD, chief medical officer at Cognition Therapeutics, presented findings from the SHIMMER study, a clinical trial of CT-1812 (zervimesine) in patients with dementia with Lewy bodies.¹

Caggiano opened by contextualizing dementia with Lewy bodies as the second most common dementia after Alzheimer disease and more prevalent than Parkinson disease, yet without any FDA-approved treatments—representing a true unmet medical need. He described the condition as presenting across cognitive, motor, and psychiatric domains, imposing substantial burden on both patients and caregivers.

CT-1812, administered as a once-daily oral pill, was designed to interrupt the basic pathophysiological process of the disease rather than target downstream symptoms. The SHIMMER trial assessed the drug's impact across the full symptom spectrum over a 6-month period.² While slowing of disease progression was observed across all symptom domains, Caggiano identified the psychiatric findings as the most clinically compelling: patients treated with CT-1812 remained essentially stable on measures of hallucinations and delusions, whereas placebo-treated patients worsened substantially. Caregiver distress attributable to these symptoms was similarly reduced in the active treatment group.

Caggiano measured psychosis outcomes using the Neuropsychiatric Inventory, a 12-item instrument, noting that hallucinations and delusions produced the strongest signal. He emphasized the particular clinical significance of this finding given that antipsychotics—while used off-label in this population—carry serious risks in dementia with Lewy bodies due to the disease's dopamine-deficient overlap with Parkinson disease, stating that "the anti-dopamine effects of the antipsychotics can lead to really quite serious side effects within these individuals."

Cognition Therapeutics planned to present the psychosis data to the FDA to seek agreement on a registrational trial pathway, with the goal that long-term CT-1812 use might delay or prevent the development of clinically significant psychosis.

Dr Caggiano is chief medical officer at Cognition Therapeutics.

References

1. Clinical trial results published: the SHIMMER study. Lewy Body Dementia Association. January 29, 2026. Accessed May 7, 2026. https://lbda.org/clinical-trial-results-published-the-shimmer-study

2. Galvin JE, Tolea MI, Scharre DW, et al. Phase 2 study of zervimesine (CT1812) in participants with mild-to-moderate dementia with Lewy bodies (DLB). Alzheimers Dement. 2025;21(12):e71004.