Dementia with Lewy bodies: Characteristics of the prodromal stage in a nationwide longitudinal cohort

Abstract

Introduction: To better characterize symptoms, neuropsychology, biomarkers, and brain MRI of prodromal dementia with Lewy bodies (Pro-DLB) patients with cognitive complaint. Method(s): Nationwide French prospective cohort of patients with cognitive complaint with a minimum follow-up of 4 years. Multicenter study including memory resource and research centers (CM2R) from France. Participants were recruited in memory clinics and screened for either isolated subjective cognitive impairment (SCI) or mild neurocognitive impairment (MCI). Eight hundred ninety-two patients were included in the Lewy Memento cohort. Probable Pro-DLB diagnosis was done using the two-criterion cut-off score among the four core clinical features. This Pro-DLB group was compared to the two other groups: the one without any core symptoms (NS group), and the one with one core symptom (1S group). A whole comprehensive cognitive battery, brain 3D volumetric MRI, CSF, FDG PET and amyloid PET were done. Result(s): The pro-DLB group was of 148 patients (16.6%). The neuropsychological profile of pro-DLB group showed regarding cognition, more multidomain (59.8%) MCI with longer speed processing, semantic and neurovisual impairment, and regarding behavior, more patients with depression, anxiety and apathy. Pro-DLB patients have also more autonomic symptoms particularly lower libido, more constipation, rhinorrhea, sicca syndrome and photophobia. Pro-DLB group had isolated lower P-Tau and no difference for amyloid PET and FDG PET. Brain MRI analysis showed widening of sulci including fronto-insular, occipital and olfactory sulci (FDR corrected). Evolution to dementia was not different between the three groups after 4 years of follow-up. Conclusion(s): Patients with prodromal DLB represents 16.6% of SCI and MCI patients which is consistent with the proportion observed at the stage of dementia. Clinical characteristics associate in addition to the key symptoms, cognitive, behavioral and autonomic symptoms. Biomarkers confirm the non-Alzheimer profile (CSF and PET). Occipital, fronto-insular and olfactive bulb involvement on brain MRI is coherent with symptoms and known neuropathology. Next step is to analyze the outcome of all these characteristics. The challenge of an accurate diagnosis of Dementia with Lewy Bodies 1. 2017 DLB criteria (Zuzana Walker, UK) 2. Prodromal DLB (John O'Brien, UK) 3. Imaging biomarkers in prodromal DLB (Frederic Blanc, France) 4. CSF biomarkers in DLB (Olivier Bousiges, France) Dementia with Lewy bodies (DLB) is an important type of neurodegenerative dementia. Compared to Alzheimer's disease (AD) clinical diagnosis of DLB can be difficult with up to 50% of cases being misdiagnosed, mainly as AD but also as vascular dementia, Frontotemporal degeneration or corticobasal syndrome. Accurate differentiation from other types of dementia as well as early detection are essential to allow appropriate management and treatment. Prodromal AD is a well-established concept, but little is known about how to identify those who will develop DLB at the prodromal or pre-dementia stage. The session will start with Dr Walker presenting a summary of the 2017 DLB Consensus Criteria that were developed to improve the clinical diagnosis of DLB. These revised DLB criteria now clearly differentiate between core clinical features and indicative biomarkers. More diagnostic emphasis is given to REM sleep behaviour disorder and to MIGB myocardial scintigraphy. The second talk by Professor O'Brien will outline the concept of prodromal DLB, discuss the variety of ways it might present, and present new data from studies which have investigated MCI-DLB as a prodromal type of DLB, showing its differentiation from MCI-AD. This will be followed by an update by Professor Blanc on various DLB imaging biomarkers and their role and limitations as prodromal biomarkers for DLB. FP-CIT SPECT, an established imaging biomarker in DLB has very good specificity but poor sensitivity in prodromal DLB. Other frequently used imaging biomarkers for DLB (MIBG, FDG PET) have not been extensively studied in prodromal DLB. New data will be presented showing interesting findings of visual assessments of the insula for the diagnosis of prodromal DLB. The session will end with a talk by Dr Bousiges who will review CSF biomarkers and how they can facilitate diagnosis. There is urgent need for research in specific biomarkers of DLB, the main being alpha-synuclein aggregates including phosphorylated and oligomeric forms of alpha-synuclein. The role of other biomarkers not directly related to alpha-synuclein will be discussed in the context of DLB diagnosis.