DESPITE being the second commonest degenerative dementia after Alzheimer’s illness, dementia with Lewy our bodies (DLB) stays underrecognised, and disease-modifying remedies are usually not presently obtainable. Specialists on the European Academy of Neurology (EAN) Congress 2026 explored the evolving understanding of DLB, together with advances in analysis, rising organic definitions of illness, and the increasing therapeutic panorama. The session, held collectively with the European Part of the Motion Dysfunction Society, was chaired by Irena Rektorová, Masaryk College, Brno, Czechia; and Dag Aarsland, King’s Faculty London, UK.
REFINING THE DIAGNOSIS OF DEMENTIA WITH LEWY BODIES
Opening the session, Evelien Lemstra, Amsterdam College Medical Centres, the Netherlands, highlighted the challenges related to recognising DLB, a heterogeneous dysfunction with various scientific displays. Though presently incurable, many signs may be handled, and early analysis stays important to allow acceptable administration. She emphasised that sufferers with DLB expertise poorer outcomes in contrast with these with Alzheimer’s illness, together with larger healthcare prices and elevated chance of nursing residence admission,1 elevating the likelihood that earlier recognition and intervention might enhance future outcomes.
Lemstra defined that DLB is characterised by α-synuclein pathology, though Alzheimer’s disease-related pathology can be concurrently current in a considerable proportion of sufferers. Not like Alzheimer’s illness, the place reminiscence and language impairment are sometimes outstanding, DLB is often related to deficits in govt perform, visuospatial talents, and a spotlight.
In 2017, the DLB Consortium printed a refined diagnostic criterion, which distinguishes clearly between scientific options and diagnostic biomarkers.2 The scientific diagnostic framework relies on attribute scientific options, with the ‘central characteristic’ being dementia.2 As well as, ‘core options’ embody cognitive fluctuations, recurrent visible hallucinations, parkinsonism, and fast eye motion sleep behaviour dysfunction (RBD). Cognitive fluctuations might contain marked variations in alertness and a spotlight, with sufferers showing comparatively effectively at some instances and markedly drowsy or confused at others. Visible hallucinations are sometimes an early and distinctive characteristic of DLB, whereas parkinsonism could also be absent at illness onset in lots of sufferers. Lemstra highlighted that many sufferers with DLB are unable to tolerate typical antipsychotic remedies as a result of neuroleptic sensitivity.
RBD, which entails irregular behaviours in the course of the dream part of sleep, can be thought-about a attribute characteristic of DLB. Extra ‘supportive options’ described within the diagnostic standards embody postural instability, syncope, autonomic dysfunction, and psychiatric signs.
The diagnostic standards additionally incorporate indicative biomarkers, together with abnormalities on dopamine transporter imaging (DATScan; GE HealthCare, Chicago, Illinois, USA), myocardial scintigraphy utilizing metaiodobenzylguanidine (MIBG), and polysomnography-confirmed RBD. Supportive biomarkers embody relative preservation of medial temporal buildings in contrast with Alzheimer’s illness, attribute findings on fluorodeoxyglucose PET, together with the cingulate island signal, and early electroencephalographic slowing.
A key scientific problem is distinguishing DLB from Parkinson’s illness dementia, given the scientific overlap between these problems. The 1-year rule stays central to this distinction: when dementia happens earlier than or inside 1 12 months of the onset of parkinsonism, the analysis is DLB, whereas Parkinson’s illness dementia refers to dementia growing after Parkinson’s illness is well-established.
TOWARDS A BIOLOGICAL DEFINITION OF LEWY BODY DISEASE
Lemstra defined that Lewy physique illness encompasses many phenotypes, together with DLB, Parkinson’s illness, Parkinson’s illness delicate cognitive impairment, Parkinson’s illness dementia, prodromal Parkinson’s illness, delicate cognitive impairment with Lewy our bodies, prodromal DLB, and idiopathic RBD. As these phenotypes are primarily clinically outlined, there may be substantial overlap in symptomology, and Lemstra defined that this may be complicated for sufferers. Subsequently, there was a shift in direction of biologically outlined illness. Relatively than defining illness solely by scientific presentation, organic classifications intention to establish the underlying protein pathology, no matter whether or not scientific signs are current.
A serious improvement enabling this transition has been the power to detect α-synuclein pathology utilizing real-time quaking-induced conversion, often known as a seeding amplification assay. This system detects the aggregation properties of α-synuclein and has demonstrated excessive sensitivity and specificity for Lewy physique ailments in chosen cohorts.3 Though cerebrospinal fluid presently supplies the strongest outcomes, α-synuclein detection in pores and skin samples and olfactory mucosa might present much less invasive diagnostic approaches sooner or later.
In 2024, two proposed organic frameworks for Lewy physique illness have been printed: the Neuronal Alpha-Synuclein Illness Built-in Staging System,4 and the SynNeurGe analysis diagnostic standards.5 This primary framework proposes that α-synuclein aggregation happens first, adopted by neurodegeneration, scientific signs, and useful impairment. The 2 most important anchors for the staging system are α-synuclein pathology measured by real-time quaking-induced conversion and dopaminergic degeneration measured by DATScan. As compared, SynNeurGe focuses on organic illness states reasonably than levels. It incorporates genetic standing, α-synucleinopathy, neurodegeneration, and scientific signs to categorise sufferers in accordance with underlying biology. Importantly, neither of those frameworks is but validated for scientific observe, and is as an alternative used as analysis standards to facilitate trial design.
Vital uncertainties stay, together with whether or not pathological processes happen in a constant sequence, how biomarker modifications relate to scientific development, and whether or not people with organic proof of α-synuclein pathology however no signs needs to be thought-about sufferers or people liable to future illness. Moreover, Lemstra famous that Alzheimer’s co-pathology contributes to illness development and survival in DLB,6 highlighting the significance of incorporating co-pathologies into future organic classification frameworks.
CURRENT TREATMENTS AND THE SEARCH FOR DISEASE-MODIFYING THERAPIES
Aarsland highlighted the restricted proof base for managing DLB. At present, the strongest proof helps cholinesterase inhibitors, with rivastigmine and donepezil demonstrating helpful results in DLB. These remedies are typically effectively tolerated and stay the mainstay of remedy, though the supporting research have been carried out roughly 2 many years in the past, highlighting the necessity for brand spanking new approaches.
Psychosis stays a serious remedy problem. Proof for antipsychotic use particularly in DLB is proscribed, though quetiapine and clozapine seem least prone to worsen parkinsonism, in accordance principally to anecdotal proof, Aarsland defined.
Past symptomatic therapies, a number of disease-modifying methods are underneath investigation. Given the central function of α-synuclein pathology in DLB, a number of approaches intention to cut back α-synuclein manufacturing, forestall aggregation, restrict its unfold, or improve degradation. Nonetheless, sturdy proof for these methods stays restricted.
However, Aarsland highlighted a number of Section II trials investigating completely different therapeutic approaches, together with servimecine (CT1812), neflamapimod, and nilotinib, which have generated encouraging early findings. For instance, servimecine was investigated in 130 sufferers with mild-to-moderate Lewy physique illness over 6 months.7 The examine met its major endpoints of security and tolerability, with encouraging numerical enhancements throughout behavioural, useful, cognitive, and movement-related measures, though no results have been noticed on plasma biomarkers.
One other examine highlighted by Aarsland was a Section II trial of nilotinib involving 43 sufferers with DLB over 6 months.8 Though primarily designed to evaluate pharmacokinetics, the examine reported enhancements in a number of scientific and biomarker secondary measures, together with a lowered variety of falls, improved dopamine and Alzheimer’s-related biomarkers, and improved cognition in contrast with placebo.
THE FUTURE OF DLB RESEARCH
Aarsland famous that there are presently round 40 lively trials in Lewy physique illness, with 11 together with DLB populations. Nonetheless, scientific trials stay difficult because of the lack of a universally accepted consequence measure. Signs fluctuate significantly between sufferers, making it troublesome to detect remedy results. Initiatives such because the Core End result Set for DLB9 and the Lewy Physique Dementia‐Area Ranking Scale (LBD‐DRS)10 intention to deal with these limitations. Biomarkers may rework future trials. α-synuclein seeding amplification assays might assist affected person stratification, whereas quantitative measures of α-synuclein sign might ultimately present consequence measures for disease-modifying therapies.
Concluding the session, Aarsland emphasised that the sphere is transferring in direction of biologically primarily based illness classification, the place sufferers might finally be characterised by their particular person patterns of protein pathology reasonably than conventional scientific diagnoses. This might allow personalised combos of therapies concentrating on particular pathological processes. Though DLB analysis stays behind that of Alzheimer’s illness and Parkinson’s illness, rising trial exercise and advances in biomarkers supply the prospect of extra focused remedies sooner or later.
