Dystonia

Updates on Dystonia: Definitions, Nomenclature, Clinical Classification, and Etiology

• Dystonia is a group of heterogeneous movement disorders that range from isolated dystonia to multi-systemic disorders.

• Definitions, nomenclature, and classifications of dystonia have been refined and adapted to reflect novel findings and increasing knowledge about the clinical, etiologic, and scientific background of dystonia.

• Dystonia is suggested to be classified according to two axes: the first axis offers precise categories for the clinical presentation grouped into age at onset, body distribution, temporal pattern, and associated features, while the second etiologic axis discriminates pathological findings, inheritance patterns, mode of acquisition, or unknown causality.

• The recent recommendations regarding terminology and nomenclature of inherited forms of dystonia and related syndromes are illustrated in this article.

• Harmonized, specific, and internationally widely used classifications provide the basis for future systematic dystonia research, as well as for more personalized patient counseling and treatment approaches.

• Dystonia is the third most common movement disorder after Parkinson’s disease and essential tremor.

• Age at onset is of great importance for the establishment of the diagnosis of a specific form of dystonia, as well as for patient counseling and care due to its prognostic value.

• Children suffering from dystonia are more likely to have a detectable cause and a tendency of the dystonia to generalize, whereas dystonic signs in adulthood are more likely to remain focal.

• The clinical presentation of dystonia can manifest in any given region of the body, and effective treatments are available for the majority of patients.

• The pattern of distribution may change over time, leading to involvement of additional dystonic regions.

• Focal, segmental, multifocal, and generalized dystonia are the classifications based on the number of affected body regions.

• The International Parkinson and Movement Disorder Society (MDS) Task Force recommends a designation assignment for genetically confirmed dystonia cases, which includes appropriate phenotype prefix, confirmation by two independent groups, and gene name as the number suffix.

• A certain threshold of evidence for a genotype–phenotype correlation has to be reached to assign a locus symbol.Dystonia: Definition, Classification, and Etiology

• Dystonia is a movement disorder characterized by sustained or intermittent muscle contractions that cause abnormal movements or postures.

• Dystonia can be classified based on body distribution, temporal pattern, and associated features.

• Body distribution includes focal, segmental, multifocal, generalized, and hemidystonia.

• Temporal pattern includes persistent, paroxysmal, diurnal fluctuations, and action-specific.

• Associated features include dystonia combined with myoclonus, parkinsonism, or other movement disorders, and can be classified as isolated, combined, or complex dystonia.

• The etiology of dystonia can be based on the contribution of the nervous system and the presence of genetic or acquired origin.

• Inherited dystonia can be autosomal dominant, autosomal recessive, X-linked recessive, or mitochondrial.

• Acquired dystonia can be caused by perinatal brain injury, infection/inflammation, drugs, toxic substances, vascular issues, neoplastic conditions, brain injury, and functional causes.

• Dystonia can also be of unknown etiology, which can be further divided into sporadic and familial forms.

• The classification of dystonia is constantly evolving as new information arises.

• A specific diagnosis can help determine a progression pattern and may allow for a better prediction of response to treatment.

• Genetic risk factors could also play a role in the development of dystonia.Dystonia Updates: Definition, Nomenclature, Clinical Classification, and Etiology

• Dystonia is a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive, movements, postures, or both.

• Dystonia can be classified based on age of onset, body distribution, and etiology.

• Primary dystonia is a form of dystonia where there is no detectable underlying cause, while secondary dystonia is caused by an identifiable insult to the nervous system.

• The classification of dystonia has evolved over the years, with the most recent consensus update providing a comprehensive and specific description of the spectrum of signs and related information for patients, clinicians, caregivers, and geneticists.

• Several genes have been implicated in the development of dystonia, with mutations in TOR1A, THAP1, ANO3, GNAL, and ATP1A3 being the most common causes of inherited dystonia.

• Genetic forms of dystonia only explain a minority of cases, and the majority of patients will not have a monogenic origin of dystonia.

• The prevalence and phenomenology of clinical characteristics, such as tremor, in dystonia can be influenced by various factors that are yet to be fully understood.

• Large cross-sectional studies have been conducted to identify factors influencing the prevalence and phenomenology of clinical characteristics, such as tremor, in dystonia.

• Assembly of data on dystonia patients has evolved greatly over the years, leading to the ability to conduct large cross-sectional studies that will enable the identification of factors influencing the prevalence and phenomenology of clinical characteristics, such as tremor, in dystonia.

• Complex systems biology approaches may lead to the development of further means of categorization of dystonia patients in the future.

• The classifications of dystonia enable the detection of certain patterns and thus facilitate the establishment of a specific diagnosis, and can be the starting point for future refinements and additions, stemming from scientific discoveries in clinical research, basic science and system biology approaches, genetic analyses, and treatment development.

• Ultimately, the identification and integration of all pieces of the puzzle will lead to an improved understanding of dystonia and patient care.A Comprehensive Review of Dystonia: Genetics, Pathology, and Clinical Considerations

• Dystonia is a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal postures or repetitive movements.

• Dystonia can be classified into primary or secondary, depending on whether it is idiopathic or associated with another underlying condition.

• There are various forms of dystonia, including focal, segmental, multifocal, generalized, and hemidystonia, each with different clinical features and underlying causes.

• Genetic factors play a significant role in the development of dystonia, with over 20 genes identified as associated with different forms of the disorder.

• Pathologically, dystonia is characterized by abnormal activity in the basal ganglia and other regions of the brain involved in motor control, including the cerebellum and brainstem.

• Non-motor symptoms, such as psychiatric comorbidities and autonomic dysfunction, are common in patients with dystonia and can significantly impact quality of life.

• Diagnosis of dystonia relies on clinical evaluation, with imaging and genetic testing used to confirm the diagnosis and identify underlying causes.

• Treatment of dystonia is often challenging and may involve a combination of pharmacological, surgical, and rehabilitative interventions, depending on the severity and underlying cause of the disorder.

• Different forms of dystonia have distinct clinical features and underlying causes, and accurate diagnosis is crucial for appropriate management.

• Research on the genetics and pathophysiology of dystonia is ongoing, with the hope of developing more effective treatments and ultimately a cure for this debilitating disorder.

• There is a need for better understanding and awareness of dystonia, particularly among healthcare professionals, to improve diagnosis and management of this complex disorder.

• Further research is needed to better understand the complex interplay between genetic and environmental factors in the development of dystonia.

Advances in Diagnosis and Treatment of Dementia with Lewy Bodies

• Dementia with Lewy bodies (DLB) is a specific presentation of a pathological α-synucleinopathy and is distinct from Lewy body dementia, which includes Parkinson’s disease dementia.

• Recent advances include updated diagnostic criteria, recognition of prodromal DLB states, and identification of biomarkers for DLB.

• Mild cognitive impairment form of DLB has research criteria published in 2020.

• Concomitant Alzheimer’s disease pathology in individuals with DLB is common, which has implications for biomarker use and expected progression.

• Median survival after DLB diagnosis is 3-4 years, but there are rapidly and slowly progressive forms.

• Clinical trials for DLB have increased over the last 5 years, targeting both symptoms and underlying pathology.

• Effective therapies for DLB remain an unmet need.

• The vocabulary for DLB causes confusion, and it is variably categorized as both an ‘atypical parkinsonism’ and an ‘Alzheimer-disease related dementia’ (ADRD).

• Lewy body dementia and DLB are further distinct from Lewy body disease (LBD), which is the term used to describe the pathological finding of Lewy bodies on postmortem examination.

• The diagnostic criteria controversy remains unresolved, with research studies variably using the 2015 MDS-PD Criteria, the 2017 DLB criteria, or a combination.

• Clinicians now make the diagnosis of possible or probable DLB based on the presence of core clinical features and indicative biomarkers.

• Additional ‘supportive’ clinical features and biomarkers do not currently have sufficient sensitivity or specificity for formal inclusion in the DLB criteria, but they can provide additional evidence supporting a DLB diagnosis.Biomarkers and Diagnostic Criteria for Dementia with Lewy Bodies

• Dementia with Lewy bodies (DLB) is a type of dementia characterized by cognitive, motor, and psychiatric symptoms.

• DLB has multiple types, including brainstem-predominant, transitional (limbic), and diffuse (neocortical) forms associated with increasing degrees of pathological burden.

• DLB diagnosis involves evaluating the degree of Lewy-related pathology and the amount of Alzheimer's disease (AD) neuropathological change.

• AD neuropathological change is common in individuals diagnosed clinically with DLB, and different distributions of α-synuclein and tau pathology associate with the phenotypic expression of DLB.

• Prodromal features of synucleinopathies include REM sleep without atonia, olfactory dysfunction, dysautonomia, and psychiatric disturbance, and mild cognitive impairment (MCI) can also precede the dementia of DLB.

• Research criteria for prodromal DLB describe three prodromal phenotypes of DLB: MCI-onset, delirium-onset, and psychiatric-onset.

• Biomarkers can be used in clinical care to help with differential diagnosis and prognosis and in research to help with participant selection and assessing therapeutic response.

• Neuroimaging techniques, such as MRI, DAT imaging, and PET imaging, can be used in DLB diagnosis and research.

• CSF testing for evidence of AD co-pathology using Aβ42, total tau (t-tau), and phosphorylated tau (p-tau) levels is used in DLB research.

• CSF α-synuclein real-time quaking-induced conversion (RT-QuIC) assays have high sensitivity and specificity in individuals with DLB and MCI-LB.

• Plasma and serum α-synuclein levels are under study as potential biomarkers in synucleinopathies, but blood biomarkers remain research-only at the present time.

• Skin biopsy is now available through some commercial laboratories, but the role that these tests play in routine clinical diagnosis is yet to be established.Management and Prognosis of Dementia with Lewy Bodies

• Skin biopsies can be used to identify pathological α-synuclein in individuals with DLB, PD, and other synucleinopathies.

• EEG findings can serve as a supportive biomarker in DLB criteria and a potential biomarker in MCI-LB criteria.

• The mean survival time post-diagnosis in individuals with DLB is 4.11 ± 4.10 years, shorter than in individuals with AD dementia.

• Rapid and slowly progressive forms of DLB exist, with diverse experiences.

• Failure to thrive is the most commonly reported cause of death in individuals with DLB, followed by swallowing difficulties associated with aspiration and pneumonia.

• There is currently no DLB-specific guidance for predicting end of life, and hospice use may not be sensitive.

• There are no disease-modifying therapies for DLB, and research attempting to slow the progression of neurodegeneration in synucleinopathies focuses primarily on individuals with PD.

• Cholinesterase inhibitors have the most evidence for use for cognitive impairment in DLB, with mixed evidence for memantine.

• Nonpharmacological interventions are recommended as the first-line approach for treating psychosis in DLB, with pharmacological therapy recommended only if symptoms are severe or distressing.

• Levodopa monotherapy is generally used to treat parkinsonism in DLB, with zonisamide used as an adjunctive therapy in Japan.

• Autonomic function in individuals with DLB is critical, but an evidence base for DLB-specific care is lacking.

• Treating sialorrhea, urinary dysfunction, and orthostatic hypotension in DLB relies on nonpharmacological therapies as first-line therapy, with pharmacological therapy used if needed.Recent Advances in Dementia with Lewy Bodies: Diagnosis, Prognosis, and Treatment

• Dementia with Lewy Bodies (DLB) is a neurodegenerative disorder that affects approximately 1.5 million people worldwide, characterized by the accumulation of alpha-synuclein protein in the brain.

• DLB is underrecognized, with misdiagnosis rates as high as 30-50%, and key diagnostic criteria were recently updated by the DLB Consortium in 2017 to improve accuracy.

• Prodromal DLB states, including Mild Cognitive Impairment with Lewy Bodies (MCI-LB), have been identified, and there is a need for biomarkers to assist in diagnosis, prognosis, and identification of co-pathology.

• Neuropathological studies have shown that DLB is a heterogeneous disorder, with varying degrees of alpha-synuclein, tau, and beta-amyloid pathology, and different subtypes of DLB have been proposed based on these findings.

• The risk of developing DLB is increased in individuals with REM sleep behavior disorder (RBD) and other prodromal states, and biomarkers such as skin alpha-synuclein aggregation seeding activity and CSF tau and beta-amyloid levels have shown promise in predicting cerebral synucleinopathy in autopsied Lewy body disorders.

• End-of-life considerations for DLB include a higher incidence of sudden death and the need for careful management of medications that can worsen symptoms.

• There is currently no disease-modifying therapy for DLB, but several clinical trials are underway, including those targeting alpha-synuclein, glucocerebrosidase, and phosphodiesterase 9, and a phase III study of the AscenD-LB study is planned.

• Symptomatic therapies for DLB include cholinesterase inhibitors, memantine, and antipsychotics (with caution due to increased sensitivity to side effects), and several clinical trials of diverse mechanisms of action are completed or underway.

• DLB research priorities identified by caregivers and individuals with DLB include improved diagnosis and treatment, increased public awareness, and better support for caregivers.

• Lewy body dementia research is supported by grants from the National Institute on Aging (NIA) and the Florida Department of Health, as well as private research funds.

• DLB remains an unmet need for effective therapies, and further research is needed to improve diagnosis, prognosis, and treatment.

• The author of the review conceptualized, drafted, and revised the article and declared no financial support for the research, authorship, and/or publication of this article.

Advances in Diagnosis and Treatment of Dementia with Lewy Bodies

• Dementia with Lewy bodies (DLB) is a specific presentation of a pathological α-synucleinopathy and is distinct from Lewy body dementia, which includes Parkinson’s disease dementia.

• Recent advances in DLB include updated diagnostic criteria, recognition of prodromal DLB states, and identification of concomitant Alzheimer’s disease pathology.

• Research criteria for the mild cognitive impairment form of DLB were published in 2020, and identifying biomarkers for DLB is an active area of research.

• DLB has a median survival of 3-4 years, but there are rapidly and slowly progressive forms, and most individuals die of complications of the disease.

• Clinical trials for individuals with DLB have increased over the last 5 years, targeting both symptoms and underlying pathology, but effective therapies remain an unmet need.

• The vocabulary for DLB, Lewy body dementia, and Lewy body disease can cause confusion, and DLB is variably categorized as both an ‘atypical parkinsonism’ and an ‘Alzheimer-disease related dementia’ (ADRD).

• The diagnostic criteria for DLB were updated in 2017, and clinicians now diagnose possible or probable DLB based on the presence of core clinical features and indicative biomarkers.

• Supportive clinical features and biomarkers provide additional evidence supporting a DLB diagnosis.

• Diagnosis relies on a comprehensive history and physical examination assessing core and supportive features of DLB, and other tests and biomarkers, such as polysomnography and dopamine transporter imaging, may be used by specialists.

• Most cases of DLB are missed, and misdiagnosis as Alzheimer’s disease is common.

• DLB is distinguished from Parkinson’s disease dementia by the timing of symptom onset, and the diagnostic criteria controversy remains unresolved.

• Maintaining DLB and Parkinson’s disease dementia as separate phenotypes has important implications for patient care and research into pathophysiology, genetics, prodromal states, and potentially treatment.Biomarkers and Diagnosis of Dementia with Lewy Bodies

• Lewy body disease has multiple types with varying degrees of pathological burden.

• AD neuropathological change is common in individuals diagnosed clinically with DLB.

• Different distributions of α-synuclein and tau pathology associate with the phenotypic expression of DLB.

• Prodromal features of synucleinopathies include RBD/REM sleep without atonia, olfactory dysfunction, dysautonomia, and psychiatric disturbance.

• Mild cognitive impairment (MCI) can precede the dementia of DLB and research criteria for prodromal DLB were published in 2020.

• Structural imaging with MRI is used in DLB to evaluate for findings suggestive of AD co-pathology.

• DAT imaging can be helpful to help diagnose DLB, particularly if parkinsonism is equivocal on examination.

• Generalized low uptake on SPECT/PET perfusion/metabolism scans is a supportive biomarker in the 2017 DLB criteria.

• Amyloid and tau PET imaging are used in DLB to help with differential diagnosis or assess the degree of suspected AD co-pathology.

• CSF testing in DLB is primarily used on a research basis and primarily to assess for evidence of AD co-pathology.

• CSF α-synuclein real-time quaking-induced conversion (RT-QuIC) assays have high sensitivity and specificity in individuals with DLB.

• Plasma and serum α-synuclein levels are under study as potential biomarkers in synucleinopathies.Management and Prognosis of Dementia with Lewy Bodies

• Skin biopsies can identify pathological α-synuclein in DLB patients and are an area of active research.

• EEG can serve as a supportive biomarker in DLB diagnosis, but its role in routine clinical practice is yet to be established.

• DLB has a mean survival time post-diagnosis of 4.11 ± 4.10 years, shorter than AD dementia.

• Rapid and slowly progressive forms of DLB exist, with diverse experiences among patients.

• Failure to thrive is the most commonly reported cause of death in DLB, followed by swallowing difficulties associated with aspiration and pneumonia.

• Clinicians should assess for suicide risk factors in DLB patients and treat possible contributors like psychosis and depression when identified.

• Hospice use in DLB patients varies, with only 40% of families reporting clinicians discussing what to expect at the end of life.

• There are no disease-modifying therapies for DLB, and treatment relies on studies in PD and AD and expert consensus.

• Cholinesterase inhibitors donepezil and rivastigmine have the most evidence for use for cognitive impairment in DLB.

• Non-pharmacological interventions are recommended as the first-line approach for treating psychosis in DLB, with pharmacological therapy recommended only if symptoms are severe or distressing.

• Levodopa monotherapy is generally used to treat parkinsonism in DLB, with zonisamide as an adjunctive treatment in Japan.

• Treating autonomic function in DLB patients is critical, but an evidence base for DLB-specific care is lacking. Non-pharmacological therapies are first-line therapy, with pharmacological therapy needed only if non-pharmacological interventions fail.Recent Advances in Dementia with Lewy Bodies: Diagnosis, Prognosis, and Therapy

• Dementia with Lewy bodies (DLB) is a common neurodegenerative disorder characterized by cognitive impairment, parkinsonism, and visual hallucinations.

• Updated diagnostic criteria for DLB have been developed, including a focus on prodromal DLB states such as mild cognitive impairment with Lewy bodies (MCI-LB).

• Biomarkers are being developed to assist with diagnosis, prognosis, and identification of co-pathology, although more research is needed in this area.

• DLB is often underrecognized and misdiagnosed, leading to suboptimal care for patients and their families.

• There is overlap between DLB and other neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease, and DLB may coexist with these disorders.

• Therapies for slowing the disease and treating its various symptoms are an unmet need, although there are several ongoing clinical trials for disease-modifying and symptomatic therapies.

• Symptomatic therapies being studied include drugs targeting cognition, psychosis, and motor symptoms, such as RVT-101/intepirdine, E2027, and NYX-458.

• DLB is associated with the accumulation of alpha-synuclein, tau, and beta-amyloid proteins in the brain, and research is ongoing to better understand the underlying pathology.

• Prodromal DLB states, such as MCI-LB, can progress to DLB or other neurodegenerative disorders, and early detection and intervention may be important for improving outcomes.

• Biomarkers are being developed to assist with diagnosis, prognosis, and identification of co-pathology, although more research is needed in this area.

• Caregivers and individuals with DLB prioritize research on improving diagnosis, developing effective treatments, and addressing non-cognitive symptoms.

• DLB research is supported by various organizations and institutions, including the National Institute on Aging, the Lewy Body Dementia Association, and the Alzheimer's Therapeutic Research Institute/Alzheimer's Clinical Trials Consortium.

Advances in Diagnosis and Treatment of Dementia with Lewy Bodies

• Dementia with Lewy bodies (DLB) is a specific presentation of a pathological α-synucleinopathy and is distinct from Lewy body dementia, which includes Parkinson’s disease dementia.

• Recent advances in DLB include updated diagnostic criteria, recognition of prodromal DLB states, and identification of concomitant Alzheimer’s disease pathology.

• Research criteria for the mild cognitive impairment form of DLB were published in 2020, and identifying biomarkers for DLB is an active area of research.

• DLB has a median survival of 3-4 years, but there are rapidly and slowly progressive forms, and most individuals die of complications of the disease.

• Clinical trials for individuals with DLB have increased over the last 5 years, targeting both symptoms and underlying pathology, but effective therapies remain an unmet need.

• The vocabulary for DLB, Lewy body dementia, and Lewy body disease can cause confusion, and DLB is variably categorized as both an ‘atypical parkinsonism’ and an ‘Alzheimer-disease related dementia’ (ADRD).

• The diagnostic criteria for DLB were updated in 2017, and clinicians now diagnose possible or probable DLB based on the presence of core clinical features and indicative biomarkers.

• Supportive clinical features and biomarkers provide additional evidence supporting a DLB diagnosis.

• Diagnosis relies on a comprehensive history and physical examination assessing core and supportive features of DLB, and other tests and biomarkers, such as polysomnography and dopamine transporter imaging, may be used by specialists.

• Most cases of DLB are missed, and misdiagnosis as Alzheimer’s disease is common.

• DLB is distinguished from Parkinson’s disease dementia by the timing of symptom onset, and the diagnostic criteria controversy remains unresolved.

• Maintaining DLB and Parkinson’s disease dementia as separate phenotypes has important implications for patient care and research into pathophysiology, genetics, prodromal states, and potentially treatment.Biomarkers and Diagnosis of Dementia with Lewy Bodies

• Lewy body disease has multiple types with varying degrees of pathological burden.

• AD neuropathological change is common in individuals diagnosed clinically with DLB.

• Different distributions of α-synuclein and tau pathology associate with the phenotypic expression of DLB.

• Prodromal features of synucleinopathies include RBD/REM sleep without atonia, olfactory dysfunction, dysautonomia, and psychiatric disturbance.

• Mild cognitive impairment (MCI) can precede the dementia of DLB and research criteria for prodromal DLB were published in 2020.

• Structural imaging with MRI is used in DLB to evaluate for findings suggestive of AD co-pathology.

• DAT imaging can be helpful to help diagnose DLB, particularly if parkinsonism is equivocal on examination.

• Generalized low uptake on SPECT/PET perfusion/metabolism scans is a supportive biomarker in the 2017 DLB criteria.

• Amyloid and tau PET imaging are used in DLB to help with differential diagnosis or assess the degree of suspected AD co-pathology.

• CSF testing in DLB is primarily used on a research basis and primarily to assess for evidence of AD co-pathology.

• CSF α-synuclein real-time quaking-induced conversion (RT-QuIC) assays have high sensitivity and specificity in individuals with DLB.

• Plasma and serum α-synuclein levels are under study as potential biomarkers in synucleinopathies.Management and Prognosis of Dementia with Lewy Bodies

• Skin biopsies can identify pathological α-synuclein in DLB patients and are an area of active research.

• EEG can serve as a supportive biomarker in DLB diagnosis, but its role in routine clinical practice is yet to be established.

• DLB has a mean survival time post-diagnosis of 4.11 ± 4.10 years, shorter than AD dementia.

• Rapid and slowly progressive forms of DLB exist, with diverse experiences among patients.

• Failure to thrive is the most commonly reported cause of death in DLB, followed by swallowing difficulties associated with aspiration and pneumonia.

• Clinicians should assess for suicide risk factors in DLB patients and treat possible contributors like psychosis and depression when identified.

• Hospice use in DLB patients varies, with only 40% of families reporting clinicians discussing what to expect at the end of life.

• There are no disease-modifying therapies for DLB, and treatment relies on studies in PD and AD and expert consensus.

• Cholinesterase inhibitors donepezil and rivastigmine have the most evidence for use for cognitive impairment in DLB.

• Non-pharmacological interventions are recommended as the first-line approach for treating psychosis in DLB, with pharmacological therapy recommended only if symptoms are severe or distressing.

• Levodopa monotherapy is generally used to treat parkinsonism in DLB, with zonisamide as an adjunctive treatment in Japan.

• Treating autonomic function in DLB patients is critical, but an evidence base for DLB-specific care is lacking. Non-pharmacological therapies are first-line therapy, with pharmacological therapy needed only if non-pharmacological interventions fail.Recent Advances in Dementia with Lewy Bodies: Diagnosis, Prognosis, and Therapy

• Dementia with Lewy bodies (DLB) is a common neurodegenerative disorder characterized by cognitive impairment, parkinsonism, and visual hallucinations.

• Updated diagnostic criteria for DLB have been developed, including a focus on prodromal DLB states such as mild cognitive impairment with Lewy bodies (MCI-LB).

• Biomarkers are being developed to assist with diagnosis, prognosis, and identification of co-pathology, although more research is needed in this area.

• DLB is often underrecognized and misdiagnosed, leading to suboptimal care for patients and their families.

• There is overlap between DLB and other neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease, and DLB may coexist with these disorders.

• Therapies for slowing the disease and treating its various symptoms are an unmet need, although there are several ongoing clinical trials for disease-modifying and symptomatic therapies.

• Symptomatic therapies being studied include drugs targeting cognition, psychosis, and motor symptoms, such as RVT-101/intepirdine, E2027, and NYX-458.

• DLB is associated with the accumulation of alpha-synuclein, tau, and beta-amyloid proteins in the brain, and research is ongoing to better understand the underlying pathology.

• Prodromal DLB states, such as MCI-LB, can progress to DLB or other neurodegenerative disorders, and early detection and intervention may be important for improving outcomes.

• Biomarkers are being developed to assist with diagnosis, prognosis, and identification of co-pathology, although more research is needed in this area.

• Caregivers and individuals with DLB prioritize research on improving diagnosis, developing effective treatments, and addressing non-cognitive symptoms.

• DLB research is supported by various organizations and institutions, including the National Institute on Aging, the Lewy Body Dementia Association, and the Alzheimer's Therapeutic Research Institute/Alzheimer's Clinical Trials Consortium.

Advances in Diagnosis and Treatment of Dementia with Lewy Bodies

• Dementia with Lewy bodies (DLB) is a specific presentation of a pathological α-synucleinopathy and is distinct from Lewy body dementia, which includes Parkinson’s disease dementia.

• Recent advances in DLB include updated diagnostic criteria, recognition of prodromal DLB states, and identification of concomitant Alzheimer’s disease pathology.

• Research criteria for the mild cognitive impairment form of DLB were published in 2020, and identifying biomarkers for DLB is an active area of research.

• DLB has a median survival of 3-4 years, but there are rapidly and slowly progressive forms, and most individuals die of complications of the disease.

• Clinical trials for individuals with DLB have increased over the last 5 years, targeting both symptoms and underlying pathology, but effective therapies remain an unmet need.

• The vocabulary for DLB, Lewy body dementia, and Lewy body disease can cause confusion, and DLB is variably categorized as both an ‘atypical parkinsonism’ and an ‘Alzheimer-disease related dementia’ (ADRD).

• The diagnostic criteria for DLB were updated in 2017, and clinicians now diagnose possible or probable DLB based on the presence of core clinical features and indicative biomarkers.

• Supportive clinical features and biomarkers provide additional evidence supporting a DLB diagnosis.

• Diagnosis relies on a comprehensive history and physical examination assessing core and supportive features of DLB, and other tests and biomarkers, such as polysomnography and dopamine transporter imaging, may be used by specialists.

• Most cases of DLB are missed, and misdiagnosis as Alzheimer’s disease is common.

• DLB is distinguished from Parkinson’s disease dementia by the timing of symptom onset, and the diagnostic criteria controversy remains unresolved.

• Maintaining DLB and Parkinson’s disease dementia as separate phenotypes has important implications for patient care and research into pathophysiology, genetics, prodromal states, and potentially treatment.Biomarkers and Diagnosis of Dementia with Lewy Bodies

• Lewy body disease has multiple types with varying degrees of pathological burden.

• AD neuropathological change is common in individuals diagnosed clinically with DLB.

• Different distributions of α-synuclein and tau pathology associate with the phenotypic expression of DLB.

• Prodromal features of synucleinopathies include RBD/REM sleep without atonia, olfactory dysfunction, dysautonomia, and psychiatric disturbance.

• Mild cognitive impairment (MCI) can precede the dementia of DLB and research criteria for prodromal DLB were published in 2020.

• Structural imaging with MRI is used in DLB to evaluate for findings suggestive of AD co-pathology.

• DAT imaging can be helpful to help diagnose DLB, particularly if parkinsonism is equivocal on examination.

• Generalized low uptake on SPECT/PET perfusion/metabolism scans is a supportive biomarker in the 2017 DLB criteria.

• Amyloid and tau PET imaging are used in DLB to help with differential diagnosis or assess the degree of suspected AD co-pathology.

• CSF testing in DLB is primarily used on a research basis and primarily to assess for evidence of AD co-pathology.

• CSF α-synuclein real-time quaking-induced conversion (RT-QuIC) assays have high sensitivity and specificity in individuals with DLB.

• Plasma and serum α-synuclein levels are under study as potential biomarkers in synucleinopathies.Management and Prognosis of Dementia with Lewy Bodies

• Skin biopsies can identify pathological α-synuclein in DLB patients and are an area of active research.

• EEG can serve as a supportive biomarker in DLB diagnosis, but its role in routine clinical practice is yet to be established.

• DLB has a mean survival time post-diagnosis of 4.11 ± 4.10 years, shorter than AD dementia.

• Rapid and slowly progressive forms of DLB exist, with diverse experiences among patients.

• Failure to thrive is the most commonly reported cause of death in DLB, followed by swallowing difficulties associated with aspiration and pneumonia.

• Clinicians should assess for suicide risk factors in DLB patients and treat possible contributors like psychosis and depression when identified.

• Hospice use in DLB patients varies, with only 40% of families reporting clinicians discussing what to expect at the end of life.

• There are no disease-modifying therapies for DLB, and treatment relies on studies in PD and AD and expert consensus.

• Cholinesterase inhibitors donepezil and rivastigmine have the most evidence for use for cognitive impairment in DLB.

• Non-pharmacological interventions are recommended as the first-line approach for treating psychosis in DLB, with pharmacological therapy recommended only if symptoms are severe or distressing.

• Levodopa monotherapy is generally used to treat parkinsonism in DLB, with zonisamide as an adjunctive treatment in Japan.

• Treating autonomic function in DLB patients is critical, but an evidence base for DLB-specific care is lacking. Non-pharmacological therapies are first-line therapy, with pharmacological therapy needed only if non-pharmacological interventions fail.Recent Advances in Dementia with Lewy Bodies: Diagnosis, Prognosis, and Therapy

• Dementia with Lewy bodies (DLB) is a common neurodegenerative disorder characterized by cognitive impairment, parkinsonism, and visual hallucinations.

• Updated diagnostic criteria for DLB have been developed, including a focus on prodromal DLB states such as mild cognitive impairment with Lewy bodies (MCI-LB).

• Biomarkers are being developed to assist with diagnosis, prognosis, and identification of co-pathology, although more research is needed in this area.

• DLB is often underrecognized and misdiagnosed, leading to suboptimal care for patients and their families.

• There is overlap between DLB and other neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease, and DLB may coexist with these disorders.

• Therapies for slowing the disease and treating its various symptoms are an unmet need, although there are several ongoing clinical trials for disease-modifying and symptomatic therapies.

• Symptomatic therapies being studied include drugs targeting cognition, psychosis, and motor symptoms, such as RVT-101/intepirdine, E2027, and NYX-458.

• DLB is associated with the accumulation of alpha-synuclein, tau, and beta-amyloid proteins in the brain, and research is ongoing to better understand the underlying pathology.

• Prodromal DLB states, such as MCI-LB, can progress to DLB or other neurodegenerative disorders, and early detection and intervention may be important for improving outcomes.

• Biomarkers are being developed to assist with diagnosis, prognosis, and identification of co-pathology, although more research is needed in this area.

• Caregivers and individuals with DLB prioritize research on improving diagnosis, developing effective treatments, and addressing non-cognitive symptoms.

• DLB research is supported by various organizations and institutions, including the National Institute on Aging, the Lewy Body Dementia Association, and the Alzheimer's Therapeutic Research Institute/Alzheimer's Clinical Trials Consortium.

Advances in Diagnosis and Treatment of Dementia with Lewy Bodies

• Dementia with Lewy bodies (DLB) is a specific presentation of a pathological α-synucleinopathy and is distinct from Lewy body dementia, which includes Parkinson’s disease dementia.

• Recent advances in DLB include updated diagnostic criteria, recognition of prodromal DLB states, and identification of concomitant Alzheimer’s disease pathology.

• Research criteria for the mild cognitive impairment form of DLB were published in 2020, and identifying biomarkers for DLB is an active area of research.

• DLB has a median survival of 3-4 years, but there are rapidly and slowly progressive forms, and most individuals die of complications of the disease.

• Clinical trials for individuals with DLB have increased over the last 5 years, targeting both symptoms and underlying pathology, but effective therapies remain an unmet need.

• The vocabulary for DLB, Lewy body dementia, and Lewy body disease can cause confusion, and DLB is variably categorized as both an ‘atypical parkinsonism’ and an ‘Alzheimer-disease related dementia’ (ADRD).

• The diagnostic criteria for DLB were updated in 2017, and clinicians now diagnose possible or probable DLB based on the presence of core clinical features and indicative biomarkers.

• Supportive clinical features and biomarkers provide additional evidence supporting a DLB diagnosis.

• Diagnosis relies on a comprehensive history and physical examination assessing core and supportive features of DLB, and other tests and biomarkers, such as polysomnography and dopamine transporter imaging, may be used by specialists.

• Most cases of DLB are missed, and misdiagnosis as Alzheimer’s disease is common.

• DLB is distinguished from Parkinson’s disease dementia by the timing of symptom onset, and the diagnostic criteria controversy remains unresolved.

• Maintaining DLB and Parkinson’s disease dementia as separate phenotypes has important implications for patient care and research into pathophysiology, genetics, prodromal states, and potentially treatment.Biomarkers and Diagnosis of Dementia with Lewy Bodies

• Lewy body disease has multiple types with varying degrees of pathological burden.

• AD neuropathological change is common in individuals diagnosed clinically with DLB.

• Different distributions of α-synuclein and tau pathology associate with the phenotypic expression of DLB.

• Prodromal features of synucleinopathies include RBD/REM sleep without atonia, olfactory dysfunction, dysautonomia, and psychiatric disturbance.

• Mild cognitive impairment (MCI) can precede the dementia of DLB and research criteria for prodromal DLB were published in 2020.

• Structural imaging with MRI is used in DLB to evaluate for findings suggestive of AD co-pathology.

• DAT imaging can be helpful to help diagnose DLB, particularly if parkinsonism is equivocal on examination.

• Generalized low uptake on SPECT/PET perfusion/metabolism scans is a supportive biomarker in the 2017 DLB criteria.

• Amyloid and tau PET imaging are used in DLB to help with differential diagnosis or assess the degree of suspected AD co-pathology.

• CSF testing in DLB is primarily used on a research basis and primarily to assess for evidence of AD co-pathology.

• CSF α-synuclein real-time quaking-induced conversion (RT-QuIC) assays have high sensitivity and specificity in individuals with DLB.

• Plasma and serum α-synuclein levels are under study as potential biomarkers in synucleinopathies.Management and Prognosis of Dementia with Lewy Bodies

• Skin biopsies can identify pathological α-synuclein in DLB patients and are an area of active research.

• EEG can serve as a supportive biomarker in DLB diagnosis, but its role in routine clinical practice is yet to be established.

• DLB has a mean survival time post-diagnosis of 4.11 ± 4.10 years, shorter than AD dementia.

• Rapid and slowly progressive forms of DLB exist, with diverse experiences among patients.

• Failure to thrive is the most commonly reported cause of death in DLB, followed by swallowing difficulties associated with aspiration and pneumonia.

• Clinicians should assess for suicide risk factors in DLB patients and treat possible contributors like psychosis and depression when identified.

• Hospice use in DLB patients varies, with only 40% of families reporting clinicians discussing what to expect at the end of life.

• There are no disease-modifying therapies for DLB, and treatment relies on studies in PD and AD and expert consensus.

• Cholinesterase inhibitors donepezil and rivastigmine have the most evidence for use for cognitive impairment in DLB.

• Non-pharmacological interventions are recommended as the first-line approach for treating psychosis in DLB, with pharmacological therapy recommended only if symptoms are severe or distressing.

• Levodopa monotherapy is generally used to treat parkinsonism in DLB, with zonisamide as an adjunctive treatment in Japan.

• Treating autonomic function in DLB patients is critical, but an evidence base for DLB-specific care is lacking. Non-pharmacological therapies are first-line therapy, with pharmacological therapy needed only if non-pharmacological interventions fail.Recent Advances in Dementia with Lewy Bodies: Diagnosis, Prognosis, and Therapy

• Dementia with Lewy bodies (DLB) is a common neurodegenerative disorder characterized by cognitive impairment, parkinsonism, and visual hallucinations.

• Updated diagnostic criteria for DLB have been developed, including a focus on prodromal DLB states such as mild cognitive impairment with Lewy bodies (MCI-LB).

• Biomarkers are being developed to assist with diagnosis, prognosis, and identification of co-pathology, although more research is needed in this area.

• DLB is often underrecognized and misdiagnosed, leading to suboptimal care for patients and their families.

• There is overlap between DLB and other neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease, and DLB may coexist with these disorders.

• Therapies for slowing the disease and treating its various symptoms are an unmet need, although there are several ongoing clinical trials for disease-modifying and symptomatic therapies.

• Symptomatic therapies being studied include drugs targeting cognition, psychosis, and motor symptoms, such as RVT-101/intepirdine, E2027, and NYX-458.

• DLB is associated with the accumulation of alpha-synuclein, tau, and beta-amyloid proteins in the brain, and research is ongoing to better understand the underlying pathology.

• Prodromal DLB states, such as MCI-LB, can progress to DLB or other neurodegenerative disorders, and early detection and intervention may be important for improving outcomes.

• Biomarkers are being developed to assist with diagnosis, prognosis, and identification of co-pathology, although more research is needed in this area.

• Caregivers and individuals with DLB prioritize research on improving diagnosis, developing effective treatments, and addressing non-cognitive symptoms.

• DLB research is supported by various organizations and institutions, including the National Institute on Aging, the Lewy Body Dementia Association, and the Alzheimer's Therapeutic Research Institute/Alzheimer's Clinical Trials Consortium.