How much do you know about Dementia with Lewy Bodies?

Advances in Diagnosis and Treatment of Dementia with Lewy Bodies

• Dementia with Lewy bodies (DLB) is a specific presentation of a pathological α-synucleinopathy, which is closely related to Parkinson's disease.

• 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.

• Identifying biomarkers for DLB is an area of active research, and cerebrospinal fluid and skin biopsy tests are now commercially available in the United States.

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

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

• DLB is distinct from Lewy body dementia, which is an umbrella term including both DLB and Parkinson's disease dementia.

• 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, with additional supportive features and biomarkers providing additional weight for a DLB diagnosis.

• Diagnosis relies largely on a comprehensive history and physical examination assessing core and supportive features of DLB, with additional tests and biomarkers uncommonly used by specialists making DLB diagnoses.

• Effective therapies for DLB remain an unmet need, and additional research and biomarkers are needed.Biomarkers and Diagnosis of Dementia with Lewy Bodies

• Dementia with Lewy bodies (DLB) is a type of dementia characterized by the presence of Lewy bodies, abnormal protein deposits in the brain.

• DLB has multiple types and can co-occur with Alzheimer's disease (AD) pathology, making diagnosis challenging.

• The degree of Lewy-related pathology and the amount of AD neuropathological change are evaluated to assess the likelihood of pathologic findings associated with a typical DLB clinical syndrome.

• DLB has prodromal features, including REM sleep behavior disorder, olfactory dysfunction, dysautonomia, psychiatric disturbance, and mild cognitive impairment (MCI).

• Research criteria for prodromal DLB have been proposed, including three prodromal phenotypes: MCI-onset, delirium-onset, and psychiatric-onset.

• Biomarkers, such as neuroimaging and fluid biomarkers, can aid in the diagnosis of DLB.

• Structural imaging with MRI can evaluate for findings suggestive of AD co-pathology and nigrostriatal degeneration.

• DAT imaging with PET and SPECT techniques can help diagnose DLB, particularly if parkinsonism is equivocal on examination.

• Generalized low uptake on SPECT/PET perfusion/metabolism scans and the cingulate island sign on FDG-PET imaging are supportive biomarkers in the 2017 DLB criteria.

• CSF testing for evidence of AD co-pathology and synucleinopathy, as well as α-synuclein RT-QuIC assays, are under investigation for use in DLB diagnosis.

• Plasma and serum α-synuclein levels are also being studied as potential biomarkers in synucleinopathies.

• Skin biopsy from proximal and distal sites can detect Lewy pathology in DLB, but its role in routine clinical diagnosis is yet to be established.Management and Progression 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, particularly slowing of the dominant EEG rhythm, can serve as a supportive biomarker in the DLB criteria and a potential biomarker in the MCI-LB criteria.

• DLB currently has no staging system, and the mean survival time postdiagnosis is 4.11 ± 4.10 years, shorter than in individuals with AD dementia.

• Rapid and slowly progressive forms of DLB exist, and most individuals die of complications of the disease, with failure to thrive as the most commonly reported cause of death.

• There is no DLB-specific guidance for predicting end of life, and clinicians often rely on local regulations for hospice use in dementia.

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

• Addressing the diverse symptoms that can be problematic in DLB, such as cognitive, neurobehavioral, motor, and autonomic symptoms, is a key principle in management.

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

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

• Levodopa monotherapy is generally used to treat parkinsonism in DLB, and zonisamide has been approved for use in Japan.

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

• Melatonin is the first-line therapy for symptoms of RBD, and managing excessive daytime sleepiness largely relies on identifying potential contributors and approaches for good sleep hygiene.Advances in the Diagnosis and Treatment of Dementia with Lewy Bodies

• Dementia with Lewy bodies (DLB) is the second most common form of neurodegenerative dementia in older adults, but it remains under-recognized and underdiagnosed.

• Updated diagnostic criteria for DLB have been developed, including the recognition of prodromal DLB states and the importance of biomarkers.

• DLB is associated with the accumulation of alpha-synuclein, tau, and beta-amyloid proteins in the brain, and the distribution of these proteins may be associated with different subtypes of DLB.

• Prodromal DLB states, including mild cognitive impairment with Lewy bodies (MCI-LB), may be identified through clinical and biomarker assessments.

• Biomarkers for DLB diagnosis and prognosis include dopamine transporter imaging, cerebrospinal fluid levels of alpha-synuclein, tau, and beta-amyloid, and skin biopsy alpha-synuclein pathology.

• Prognostic considerations for DLB include the risk of cognitive decline, dementia, and mortality, as well as the potential impact of co-pathologies such as Alzheimer's disease and vascular dementia.

• Disease-modifying therapies for DLB are under investigation, including immunotherapies targeting alpha-synuclein and other approaches to reduce protein accumulation and neuroinflammation.

• Symptomatic therapies for DLB are also being studied, including drugs targeting cognition, motor symptoms, and psychosis.

• Many symptomatic therapy trials have shown no clear efficacy, highlighting the need for further research in this area.

• Caregivers and individuals with DLB prioritize research on improving diagnosis, identifying biomarkers, and developing effective treatments for cognitive and motor symptoms.

• DLB research is supported by the National Institute on Aging, the Florida Department of Health, and private foundations.

• DLB remains an important public health challenge, with a growing need for effective diagnosis, biomarkers, and treatments to improve outcomes for individuals and families affected by this devastating condition.

Advances in Diagnosis and Treatment of Dementia with Lewy Bodies

• Dementia with Lewy bodies (DLB) is a specific presentation of a pathological α-synucleinopathy, which is closely related to Parkinson's disease.

• 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.

• Identifying biomarkers for DLB is an area of active research, and cerebrospinal fluid and skin biopsy tests are now commercially available in the United States.

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

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

• DLB is distinct from Lewy body dementia, which is an umbrella term including both DLB and Parkinson's disease dementia.

• 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, with additional supportive features and biomarkers providing additional weight for a DLB diagnosis.

• Diagnosis relies largely on a comprehensive history and physical examination assessing core and supportive features of DLB, with additional tests and biomarkers uncommonly used by specialists making DLB diagnoses.

• Effective therapies for DLB remain an unmet need, and additional research and biomarkers are needed.Biomarkers and Diagnosis of Dementia with Lewy Bodies

• Dementia with Lewy bodies (DLB) is a type of dementia characterized by the presence of Lewy bodies, abnormal protein deposits in the brain.

• DLB has multiple types and can co-occur with Alzheimer's disease (AD) pathology, making diagnosis challenging.

• The degree of Lewy-related pathology and the amount of AD neuropathological change are evaluated to assess the likelihood of pathologic findings associated with a typical DLB clinical syndrome.

• DLB has prodromal features, including REM sleep behavior disorder, olfactory dysfunction, dysautonomia, psychiatric disturbance, and mild cognitive impairment (MCI).

• Research criteria for prodromal DLB have been proposed, including three prodromal phenotypes: MCI-onset, delirium-onset, and psychiatric-onset.

• Biomarkers, such as neuroimaging and fluid biomarkers, can aid in the diagnosis of DLB.

• Structural imaging with MRI can evaluate for findings suggestive of AD co-pathology and nigrostriatal degeneration.

• DAT imaging with PET and SPECT techniques can help diagnose DLB, particularly if parkinsonism is equivocal on examination.

• Generalized low uptake on SPECT/PET perfusion/metabolism scans and the cingulate island sign on FDG-PET imaging are supportive biomarkers in the 2017 DLB criteria.

• CSF testing for evidence of AD co-pathology and synucleinopathy, as well as α-synuclein RT-QuIC assays, are under investigation for use in DLB diagnosis.

• Plasma and serum α-synuclein levels are also being studied as potential biomarkers in synucleinopathies.

• Skin biopsy from proximal and distal sites can detect Lewy pathology in DLB, but its role in routine clinical diagnosis is yet to be established.Management and Progression 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, particularly slowing of the dominant EEG rhythm, can serve as a supportive biomarker in the DLB criteria and a potential biomarker in the MCI-LB criteria.

• DLB currently has no staging system, and the mean survival time postdiagnosis is 4.11 ± 4.10 years, shorter than in individuals with AD dementia.

• Rapid and slowly progressive forms of DLB exist, and most individuals die of complications of the disease, with failure to thrive as the most commonly reported cause of death.

• There is no DLB-specific guidance for predicting end of life, and clinicians often rely on local regulations for hospice use in dementia.

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

• Addressing the diverse symptoms that can be problematic in DLB, such as cognitive, neurobehavioral, motor, and autonomic symptoms, is a key principle in management.

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

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

• Levodopa monotherapy is generally used to treat parkinsonism in DLB, and zonisamide has been approved for use in Japan.

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

• Melatonin is the first-line therapy for symptoms of RBD, and managing excessive daytime sleepiness largely relies on identifying potential contributors and approaches for good sleep hygiene.Advances in the Diagnosis and Treatment of Dementia with Lewy Bodies

• Dementia with Lewy bodies (DLB) is the second most common form of neurodegenerative dementia in older adults, but it remains under-recognized and underdiagnosed.

• Updated diagnostic criteria for DLB have been developed, including the recognition of prodromal DLB states and the importance of biomarkers.

• DLB is associated with the accumulation of alpha-synuclein, tau, and beta-amyloid proteins in the brain, and the distribution of these proteins may be associated with different subtypes of DLB.

• Prodromal DLB states, including mild cognitive impairment with Lewy bodies (MCI-LB), may be identified through clinical and biomarker assessments.

• Biomarkers for DLB diagnosis and prognosis include dopamine transporter imaging, cerebrospinal fluid levels of alpha-synuclein, tau, and beta-amyloid, and skin biopsy alpha-synuclein pathology.

• Prognostic considerations for DLB include the risk of cognitive decline, dementia, and mortality, as well as the potential impact of co-pathologies such as Alzheimer's disease and vascular dementia.

• Disease-modifying therapies for DLB are under investigation, including immunotherapies targeting alpha-synuclein and other approaches to reduce protein accumulation and neuroinflammation.

• Symptomatic therapies for DLB are also being studied, including drugs targeting cognition, motor symptoms, and psychosis.

• Many symptomatic therapy trials have shown no clear efficacy, highlighting the need for further research in this area.

• Caregivers and individuals with DLB prioritize research on improving diagnosis, identifying biomarkers, and developing effective treatments for cognitive and motor symptoms.

• DLB research is supported by the National Institute on Aging, the Florida Department of Health, and private foundations.

• DLB remains an important public health challenge, with a growing need for effective diagnosis, biomarkers, and treatments to improve outcomes for individuals and families affected by this devastating condition.

Advances in Diagnosis and Treatment of Dementia with Lewy Bodies

• Dementia with Lewy bodies (DLB) is a specific presentation of a pathological α-synucleinopathy, which is closely related to Parkinson's disease.

• 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.

• Identifying biomarkers for DLB is an area of active research, and cerebrospinal fluid and skin biopsy tests are now commercially available in the United States.

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

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

• DLB is distinct from Lewy body dementia, which is an umbrella term including both DLB and Parkinson's disease dementia.

• 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, with additional supportive features and biomarkers providing additional weight for a DLB diagnosis.

• Diagnosis relies largely on a comprehensive history and physical examination assessing core and supportive features of DLB, with additional tests and biomarkers uncommonly used by specialists making DLB diagnoses.

• Effective therapies for DLB remain an unmet need, and additional research and biomarkers are needed.Biomarkers and Diagnosis of Dementia with Lewy Bodies

• Dementia with Lewy bodies (DLB) is a type of dementia characterized by the presence of Lewy bodies, abnormal protein deposits in the brain.

• DLB has multiple types and can co-occur with Alzheimer's disease (AD) pathology, making diagnosis challenging.

• The degree of Lewy-related pathology and the amount of AD neuropathological change are evaluated to assess the likelihood of pathologic findings associated with a typical DLB clinical syndrome.

• DLB has prodromal features, including REM sleep behavior disorder, olfactory dysfunction, dysautonomia, psychiatric disturbance, and mild cognitive impairment (MCI).

• Research criteria for prodromal DLB have been proposed, including three prodromal phenotypes: MCI-onset, delirium-onset, and psychiatric-onset.

• Biomarkers, such as neuroimaging and fluid biomarkers, can aid in the diagnosis of DLB.

• Structural imaging with MRI can evaluate for findings suggestive of AD co-pathology and nigrostriatal degeneration.

• DAT imaging with PET and SPECT techniques can help diagnose DLB, particularly if parkinsonism is equivocal on examination.

• Generalized low uptake on SPECT/PET perfusion/metabolism scans and the cingulate island sign on FDG-PET imaging are supportive biomarkers in the 2017 DLB criteria.

• CSF testing for evidence of AD co-pathology and synucleinopathy, as well as α-synuclein RT-QuIC assays, are under investigation for use in DLB diagnosis.

• Plasma and serum α-synuclein levels are also being studied as potential biomarkers in synucleinopathies.

• Skin biopsy from proximal and distal sites can detect Lewy pathology in DLB, but its role in routine clinical diagnosis is yet to be established.Management and Progression 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, particularly slowing of the dominant EEG rhythm, can serve as a supportive biomarker in the DLB criteria and a potential biomarker in the MCI-LB criteria.

• DLB currently has no staging system, and the mean survival time postdiagnosis is 4.11 ± 4.10 years, shorter than in individuals with AD dementia.

• Rapid and slowly progressive forms of DLB exist, and most individuals die of complications of the disease, with failure to thrive as the most commonly reported cause of death.

• There is no DLB-specific guidance for predicting end of life, and clinicians often rely on local regulations for hospice use in dementia.

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

• Addressing the diverse symptoms that can be problematic in DLB, such as cognitive, neurobehavioral, motor, and autonomic symptoms, is a key principle in management.

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

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

• Levodopa monotherapy is generally used to treat parkinsonism in DLB, and zonisamide has been approved for use in Japan.

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

• Melatonin is the first-line therapy for symptoms of RBD, and managing excessive daytime sleepiness largely relies on identifying potential contributors and approaches for good sleep hygiene.Advances in the Diagnosis and Treatment of Dementia with Lewy Bodies

• Dementia with Lewy bodies (DLB) is the second most common form of neurodegenerative dementia in older adults, but it remains under-recognized and underdiagnosed.

• Updated diagnostic criteria for DLB have been developed, including the recognition of prodromal DLB states and the importance of biomarkers.

• DLB is associated with the accumulation of alpha-synuclein, tau, and beta-amyloid proteins in the brain, and the distribution of these proteins may be associated with different subtypes of DLB.

• Prodromal DLB states, including mild cognitive impairment with Lewy bodies (MCI-LB), may be identified through clinical and biomarker assessments.

• Biomarkers for DLB diagnosis and prognosis include dopamine transporter imaging, cerebrospinal fluid levels of alpha-synuclein, tau, and beta-amyloid, and skin biopsy alpha-synuclein pathology.

• Prognostic considerations for DLB include the risk of cognitive decline, dementia, and mortality, as well as the potential impact of co-pathologies such as Alzheimer's disease and vascular dementia.

• Disease-modifying therapies for DLB are under investigation, including immunotherapies targeting alpha-synuclein and other approaches to reduce protein accumulation and neuroinflammation.

• Symptomatic therapies for DLB are also being studied, including drugs targeting cognition, motor symptoms, and psychosis.

• Many symptomatic therapy trials have shown no clear efficacy, highlighting the need for further research in this area.

• Caregivers and individuals with DLB prioritize research on improving diagnosis, identifying biomarkers, and developing effective treatments for cognitive and motor symptoms.

• DLB research is supported by the National Institute on Aging, the Florida Department of Health, and private foundations.

• DLB remains an important public health challenge, with a growing need for effective diagnosis, biomarkers, and treatments to improve outcomes for individuals and families affected by this devastating condition.