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BRAIN HEALTH

Delusions may occur as muscarinic M1 receptors are elevated. The 4. Cognition Therapeutics, Inc. (2024, December 18). Cognition
location of these aggregates relates the underlying pathophysiology Therapeutics Announces Positive Results in Phase 2 Study of
to clinical presentation. Aggregates within neurons of the brainstem CT1812 in Dementia with Lewy Bodies. https://ir.cogrx.com/
and cerebral cortex are responsible for the impairment of cognition, press_releases/cognition-therapeutics-announces-positive-results-
thought and language resulting in early dementia and therefore, DLB; in-phase-2-study-of-ct1812-in-dementia-with-lewy-bodies/
aggregates that only occur within neurons of the brainstem lead 5. Elder, G.J., Lazar, A.S., Alfonso‐Miller, P., & Taylor, J. (2022).
initially to a diagnosis of Parkinson’s disease and then PDD as Lewy Sleep disturbances in Lewy body dementia: A systematic review.
bodies form in the cerebral cortex and lead to dementia. International Journal of Geriatric Psychiatry, 37(10). https://doi.
The prognosis for LBD patients is poor, with patients typically org/10.1002/gps.5814
living for only five to seven years after diagnosis. Delays in diagnosis 6. Jiang, Y., Alam, J.J., Gomperts, S.N., Maruff, P., Lemstra, A.W.,
or misdiagnosis, especially in the absence of visual hallucinations, Germann, U.A., Stavrides, P.H., Darji, S., Malampati, S., Peddy,
are major contributing factors and so are a lack of targeted therapies. J., Bleiwas, C., Pawlik, M., Pensalfini, A., Yang, D., Subbanna, S.,
Current interventions focus on managing the symptoms, such as using Basavarajappa, B.S., Smiley, J.F., Gardner, A., Blackburn, K., Chu,
cholinesterase inhibitors for cognitive symptoms, carbidopa-levodopa H-M., Prins, N.D., Teunissen, C.E., Harrison, J.E., Scheltens, P.,
for movement symptoms, antipsychotics such as pimavanserin for Nixon, R.A. (2022). Preclinical and randomized clinical evalu-
hallucinations, melatonin for RBD, and selective serotonin reuptake ation of the p38α kinase inhibitor neflamapimod for basal fore-
inhibitors (SSRIs) for sleep disorders. brain cholinergic degeneration. Nature Communications, 13(1).
While therapeutics that reverse disease progression or remove https://doi.org/10.1038/s41467-022-32944-3
Lewy bodies are not available, a few medications currently in clini- 7. Lemstra, A.W., & Van De Berg, W.D.J. (2025). Temporal and
cal trials show promise. For example, the exploratory phase 2 SHIM- biological heterogeneity in Lewy body disease. The Lancet
MER clinical trial, based on Cognition Therapeutic’s CT1812, which Neurology, 24(5), 378–379. https://doi.org/10.1016/s1474-
works by antagonizing sigma 2 receptor (S2R) that regulates cellular 4422(25)00113-9
damage, just reached its end point of safety and reliability. Data from 8. National Institute of Neurological Disorders and Stroke. (n.d.).
the study also showed a reduction in neuropsychiatric symptoms by Lewy body dementia. https://www.ninds.nih.gov/health-infor-
82% and a decrease in cognitive decline by 91%. Another pharmaceu- mation/disorders/lewy-body-dementia
tical in clinical trials is CervoMed’s neflamapimod, which inhibits a 9. Lizama, B.N., Kahle, J., Catalano, S.M., Caggiano, A.O., Grund-
mitogen-activated protein kinase, p38 alpha, involved in mediating man, M., & Hamby, M.E. (2023). Sigma-2 Receptors—From
inflammation and consequent loss of basal forebrain cholinergic neu- Basic Biology to Therapeutic Target: A Focus on Age-Related
rons (BFCN). Neflamapimod has been shown to improve synaptic Degenerative Diseases. International Journal of Molecular Scienc-
vesicle function and neurotransmitter release resulting in improved es, 24(7), 6251. https://doi.org/10.3390/ijms24076251
cognitive performance. In March 2025, reports following 16 weeks of 10. Matar, E., & Halliday, G.M. (2025). Biological effects of pathol-
the extension phase of the phase 2b RewinD-LB clinical trial indicat- ogies in Lewy body diseases: why timing matters. The Lancet
ed that neflamapimod significantly benefited DLB patients in terms Neurology, 24(5), 441–455. https://doi.org/10.1016/s1474-
of cognitive changes and in decreasing the incidence of falls. Several 4422(25)00085-7
other therapies for dementia and cognitive impairment are in various 11. Stallard, P.J.E., Ukraintseva, S.V., & Doraiswamy, P.M. (2025).
stages of clinical trials such as Aptinyx’s NYX-458 and Athira Pharma’s Changing story of the dementia epidemic. JAMA. https://doi.
ATH-1017. org/10.1001/jama.2025.1897
LBD remains a complex neurodegenerative condition, but ongoing 12. United States Cost of Dementia Research Team. (2025, April
research offers hope for better treatment options. While there is still a 23). The Cost of Dementia in 2025. USC Leonard D.Schaeffer
Institute for Public Policy & Government Service. https://schaef-
long way to go, each step forward brings us closer to a better quality of fer.usc.edu/research/the-cost-of-dementia-in-2025/
life for those living with LBD.

References:
1. Ciccone, I. (2025, March 13). Neflamapimod shows prom-
ising phase 2B extension data in dementia with lewy bodies. Gregory Michael Tomlinson, OMS-II, is a medical student at the
Neurology Live. https://www.neurologylive.com/view/ University of the Incarnate Word School of Osteopathic Medicine,
neflamapimod-shows-promising-phase-2b-extension-data-de- Class of 2027. He is passionate about preventative and lifestyle
mentia-lewy-bodies medicine and interested in pursuing psychiatry or neurology.
2. ClinicalTrials.gov. (n.d.) RewinD-LB - Clinical Study of
Neflamapimod in Patients with Dementia with Lewy Bodies. Ramaswamy Sharma, MS, PhD, is a Professor of Histology
https://clinicaltrials.gov/study/NCT05869669 and Pathology at the University of the Incarnate Word School
3. ClinicalTrials.gov. (n.d.). Study to Evaluate the Safety, Tolerabil- of Osteopathic Medicine. He is interested in delineating the
ity and Efficacy of CT1812 in Subjects with Mild to Moderate multiple molecular and cellular roles of melatonin in maintaining
Dementia with Lewy Bodies. https://www.clinicaltrials.gov/ our quality of life. Dr. Sharma is a member of the BCMS Publications
study/NCT05225415?term=CT1812&rank=9 Committee.
Visit us at www.bcms.org 19