Taylor, Angela

Abstract Dementia with Lewy bodies (DLB) is clinically defined by the presence of visual hallucinations, fluctuations, rapid eye movement (REM) sleep behavioral disorder, and parkinsonism. Neuropathologically, it is characterized by the presence of Lewy pathology. However, neuropathological studies have demonstrated the high prevalence of coexistent Alzheimer's disease, TAR DNA‐binding protein 43 (TDP‐43), and cerebrovascular pathologic cases. Due to their high prevalence and clinical impact on DLB individuals, clinical trials should account for these co‐pathologies in their design and selection and the interpretation of biomarkers values and outcomes. Here we discuss the frequency of the different co‐pathologies in DLB and their cross‐sectional and longitudinal clinical impact. We then evaluate the utility and possible applications of disease‐specific and disease‐nonspecific biomarkers and how co‐pathologies can impact these biomarkers. We propose a framework for integrating multi‐modal biomarker fingerprints and step‐wise selection and assessment of DLB individuals for clinical trials, monitoring target engagement, and interpreting outcomes in the setting of co‐pathologies.

Background: Dementia with Lewy bodies (DLB) is one of the most common degenerative dementias. Clinical trials for individuals with DLB are increasing. We aimed to identify commonly used outcome measures for trials in DLB. Methods: A pragmatic literature search of PubMed and clinicaltrials.gov identified interventional studies including populations with DLB. Studies were included if they enrolled participants with DLB and met the National Institutes of Health criteria for a clinical trial. Data were collected using standardized forms. Outcome measures were categorized according to core and supportive features of DLB. Results: After de-duplication, 58 trials were identified. The most common cognitive outcome measures were the Mini Mental State Examination (n=24) and Cognitive Drug Research computerized Assessment System (n=5). The Clinician’s Assessment of Fluctuations was the most commonly used measure for fluctuations (n=4). Over half of studies used the Neuropsychiatric Inventory to assess behavioral symptoms (n=31). The Unified Parkinson’s Disease Rating Scale was frequently used for motor assessment (n=23). Conclusions and Relevance: Clinical trial outcomes used in DLB are rarely validated in this population and some lack face validity. There is a need to validate existing scales in DLB and develop DLB-specific outcome measures.

Individuals with dementia with Lewy bodies (DLB) commonly die from dementia-related causes, but little is known regarding caregiver experiences during the end-of-life period in DLB. This reflects a critical knowledge gap given the high frequency of informal caregiving for individuals with dementia, high caregiver burden in DLB, and the fact that most individuals with DLB die from this disease. Investigators conducted telephone interviews with family members of individuals who died with DLB in the last 5 years. Investigators used a qualitative descriptive approach to analyze interview transcripts. Participants included 15 children, 13 spouses, and 2 other family members. Interviews averaged 31 min. Major themes included caregivers as the main drivers of care for individuals with DLB throughout the disease course and at the end of life, the impact of DLB features (e.g., fluctuations, hallucinations, and delusions) on end-of-life experiences, experiences relating to the caregiving role, death and post-death experiences, and supports employed by caregivers in the end-of-life period. End-of-life experiences for caregivers of individuals with DLB built on the accumulated burden of the disease course, where caregivers were often responsible for driving DLB care—from making the diagnosis to educating healthcare professionals and double-checking medical decisions. While some end-of-life experiences were consistent with those described in dementia palliative care more generally (e.g., financial stresses, poor sleep, being overwhelmed, and needing increased education and support), many DLB features specifically affected end-of-life caregiver experiences, such as the presence of delusions. Improving caregiver experiences at the end of life in DLB will require improved diagnosis and care for individuals with DLB throughout the disease course and also better strategies for treating behavioral symptoms. More research is needed regarding drivers of quality end-of-life experiences for individuals with DLB and their families and how drivers and strategies may differ between dementias.

ABSTRACT As members of the Lewy Body Dementia Association Scientific Advisory Council, we aim to address some of the issues raised in the article titled “Time to Redefine PD? Introductory Statement of the MDS Task Force on the Definition of Parkinson's Disease.” In particular, we suggest that the 1‐year rule distinguishing Parkinson's disease dementia from dementia with Lewy bodies is worth maintaining because it serves an important purpose in clinical practice and clinical and basic science research and when helping the lay community understand the complexity of these different clinical phenotypes. Furthermore, we believe that adding an additional diagnostic label, “PD (dementia with Lewy bodies subtype),” will confuse rather than clarify the distinction between dementia with Lewy bodies and PD or PD dementia, and will not improve management or expedite therapeutic development. We present arguments supporting our contentions. © 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.