A mysterious mind, a body in protest, and the search for answers.
Dementia with Lewy bodies is a complex brain disorder caused by the accumulation of abnormal protein deposits, called Lewy bodies, inside the brain's nerve cells. These deposits are primarily made of a misfolded protein called alpha-synuclein 2 7 . This clumping of alpha-synuclein disrupts normal cell communication and eventually leads to the death of brain cells.
Americans affected by DLB
Most common progressive dementia
Key protein involved
Dr. Denise Compton, a geriatrics neuropsychologist, notes that DLB is "widely underdiagnosed," meaning many may be living with the condition without a correct diagnosis 1 .
DLB exists on a spectrum of what clinicians call "Lewy body disease," which also includes Parkinson's disease and Parkinson's disease dementia. The distinction often comes down to a timeline of symptoms: if cognitive symptoms appear before or within a year of movement problems, it's DLB; if movement problems come first and cognitive decline follows later, it's diagnosed as Parkinson's disease dementia 5 .
While memory loss can occur in DLB, the most salient features often lie elsewhere. Clinicians look for a specific set of core and supportive symptoms to piece together the diagnostic puzzle 2 4 .
A landmark study from Johns Hopkins Medicine, published in September 2025, revealed for the first time a potential molecular connection between air pollution and an increased risk of developing Lewy body dementia 6 .
Analysis of 56.5 million U.S. hospital admissions between 2000 and 2014, using ZIP code data to estimate long-term exposure to PM2.5.
Exposed different groups of mice to PM2.5 samples from China, Europe, and the U.S. every other day for up to 10 months.
Used advanced techniques to study structural changes, cell death, and alpha-synuclein clumps in mouse brains.
"This suggests that pollution may not only trigger the build-up of toxic proteins but also drive disease-related gene expression changes in the human brain," said Dr. Shizhong Han, a lead investigator on the study 6 .
| Tool or Reagent | Primary Function in DLB Research |
|---|---|
| Alpha-Synuclein Seed Amplification Assays (SAA) | A breakthrough diagnostic tool that detects misfolded alpha-synuclein in cerebrospinal fluid 4 |
| Thioflavin Dyes | Fluorescent dyes used in SAAs that bind to aggregated proteins 4 |
| Cholinesterase Inhibitors | Frontline pharmacological treatment for cognitive decline in DLB 4 |
| Monoclonal Antibodies | Investigational antibody-based therapies designed to target protein aggregates 1 4 |
| 123I-MIBG Cardiac Scintigraphy | Biomarker test that assesses autonomic nerve function 2 |
Current management of DLB is primarily symptomatic, as there are no approved treatments that can slow or stop the underlying disease progression 4 5 .
Other global trials are exploring the repurposing of existing drugs 8 .
Identification of targets and drug candidates
Safety and dosage studies in small groups
Efficacy and side effects (Neflamapimod, CT1812, Zervimesine)
Confirmatory studies in larger populations
FDA and international agency review
The journey to understand Dementia with Lewy bodies is accelerating. Researchers are moving ever closer to unlocking the mysteries of this complex condition—from identifying potential environmental triggers like air pollution to developing sensitive diagnostic tests and targeted therapies.
Improved biomarkers and detection methods
Drugs addressing underlying pathology
Enhanced care and quality of life
"Our lives are absolutely more enriched," Susan says after James's participation in a clinical trial 9 . His story is a powerful testament to the dual value of research: it offers personal hope today while building a foundation of knowledge for a cure tomorrow.
For more information and support, please contact the Lewy Body Dementia Association (lbda.org) or the Alzheimer's Association (alz.org).