Diagnosis, treatment, clinical trials obstacles to addressing dementia with Lewy bodies

Key takeaways:

• Dementia with Lewy bodies is closely related to Parkinson’s disease dementia, which causes delays in accurate diagnosis.
• Effective clinical trials are needed to develop and advance treatment options.

PHILADELPHIA — To effectively address symptoms of dementia with Lewy bodies, the medical community must address obstacles such as accurate diagnosis, lack of treatment options and dearth of clinical trials, according to a presenter.

“It’s the second-most common cause of neurodegenerative disease, about 10% to 12% of cases,” James E. Galvin, MD, MPH, director of the Comprehensive Center for Brain Health at the University of Miami Miller School of Medicine, told attendees at the American Neurological Association annual meeting. “It’s more common in men; it’s more common as you get older; it’s faster declining than Alzheimer’s and multiple studies have shown a tremendous delay in diagnosis.”

Calling dementia with Lewy bodies (DLB) “the most common disease you never heard of,” Galvin noted its estimated incidence rates to be between 0.5 to 1.6 per 1,000 person years which accounted for 3.7% of all dementia cases, with an estimated prevalence of 0.02 to 63.5 per 1,000 person years and a combined total of individuals diagnosed in the U.S. at 1.4 million.

As such, a revised criteria for accurate diagnosis was necessary, including three core features of fluctuating cognition, recurrent visual hallucinations and REM sleep behavior disorder along with evidence of bradykinesia, rest tremor or rigidity in movement — all cardinal features of Parkinsonism.

Although there are no singular pharmacological options currently available, Galvin stated the body of knowledge extends to addressing individual DLB symptoms with medications known to be effective in treating each; however, he cautioned that a balance must be found as a particular treatment for one symptom may negatively impact or intensify another, whose treatment may subsequently impact additional symptoms.

Most importantly, Galvin said, DLB treatment must assess gaps in effective clinical trial designs, starting with clearer characterizations of prodromal disease states which enable clinicians to better separate DLB cohorts from PDD cohorts for trial enrollment, and then craft more specific multi-arm trials focusing solely on those with DLB.

Galvin noted several ongoing studies attempting to assess safety, tolerability and pharmacokinetics. The first included 34 participants involving a phosphodiesterase 9 (PDE9) inhibitor, E2027 which enhances glutamatergic synapses to mollify symptoms of DLB. The second and third trials are ongoing and in collaboration with Cognition Therapeutics and EIP Pharma, respectively, funded by grants from the National Institute on Aging, and testing small molecule therapeutics.

“(Lewy bodies) are a common cause of dementia for which there are no approved treatments in the U.S.,” Galvin said. “In order to develop treatments, we need to do a bunch of things. We have to design the best possible studies, we have to think about specific biomarkers, we need to develop specific outcomes.”