Surupa Chakraborty, Amity University Kolkata
Lewy body dementia comprises two related disorders: dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD). Dementia with Lewy bodies (DLB) is recognized as the second most common form of neurodegenerative dementias in older people. Sufficient pieces of evidence are still not available about its prognosis and natural history, which are beneficial for clinical practice and research. DLB accounts for about 20% of the elderly dementia cases diagnosed in the community with a high percentage in secondary care. The prevalence of patients suffering from DLB is likely to be higher and accompanied by shorter lifespan, accelerated cognitive decline, and increased admission to residential care than patients with Alzheimer’s disease.
Unlike Alzheimer’s disease (AD) and Parkinson’s disease (PD), DLB clinical trials face the challenges of accurate diagnosis, appropriate clinical management which are reportedly attributed to several co-morbidities, lack of biomarker standardization, fluctuations in cognitive and functional presentations, differences in specialty access and evaluations across healthcare systems and difficulty in symptoms recognition, thereby leading to the significant burden upon patients and caregivers. Clinical treatment of LBD is complex due to its wide range of symptoms such as cognitive impairment/dementia, mood disorders, apathy, autonomic dysfunction, psychosis, parkinsonism, neuropsychiatric, autonomic, sleep phenotypes, and treating either of these can give rise to new symptoms. Most therapeutic trials for DLB were focused on drugs developed for the treatment of AD and PD cognitive impairment, such as cholinesterase inhibitors, memantine, etc.
However, in recent years, there have been some noteworthy advances in the development of additional tools such as Lewy Body Composite Risk Score (LBCRS), LBDA’s diagnostic symptom checklist, DIAMOND-Lewy Toolkit and National Alzheimer’s Coordinating Center (NACC) DLB module, biomarkers for characterizing between PDD and DLB and diagnosing DLB.
Recent studies highlight that LBD clinical trial designs are optimized by:
- administering properly validated assessments, with strong test-retest reliability, sensitivity to all types and spectrum of cognitive impairment/dementia in LBD and PDD
- use of LBD composite scores, measures of global cognition, proper computerized tests, further consideration for MCI-LB studies
- patient and community engagement from early stages of clinical trials, sensitive neuropsychological tests to provide sufficient data for drug approval
- use of biomarkers, body fluids such as blood and CSF, dopamine transporter imaging for screenings, etc.
Even though several clinical trials and electrophysiological or imaging studies may provide opportunities to better assess the features of LBD, there are still no established methods to harness the potential of core features like fluctuating cognition and alertness in influencing the study outcomes. Use of EEG-like biomarkers in LBD, whether structural, functional, or fluid-based or other electrophysiological, as well as genetic subtypes of LBDs, have the potential to be tested in clinical research for patient selection, diagnosis and distinction from AD, studying outcome measures, and target engagement. More comprehensive clinical trials, as performed in frontotemporal lobar degeneration, observational research in PD, PDD, AD and DLB on donated brains for research, proper data sharing, consultation and partnership with leading industries, clinicians, researchers, government, and regulatory guidelines issued by FDA, can provide deeper insight into LBD progression and will be beneficial for the future of LBD trials.
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Source:
- Challenges and opportunities for improving the landscape for Lewy body Dementia clinical trials. Jennifer G. Goldman1* , Leah K. Forsberg2 , Bradley F. Boeve2 , Melissa J. Armstrong3 , David J. Irwin4 , Tanis J. Ferman5 , Doug Galasko6 , James E. Galvin7 , Daniel Kaufer8ˆ, James Leverenz9 , Carol F. Lippa10, Karen Marder11, Victor Abler12, Kevin Biglan13, Michael Irizarry14, Bill Keller12, Leanne Munsie13, Masaki Nakagawa15, Angela Taylor16 and Todd Graham16, (2020), Alzheimer’s Research & Therapy 12:137 https://doi.org/10.1186/s13195-020-00703-5
- New evidence on the management of Lewy body dementia.Taylor J-P, McKeith IG, Burn DJ, Boeve BF, Weintraub D, Bamford C, et al. (2020), Lancet Neurol. 19(2):157–69.https://doi.org/10.1016/S1474-4422(19)30153-X
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