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title, docid, authors, breadcrumbs, category, cmeTopicId, documentVersionId, imageCount, lastUpdated, pageDescription, pageKeywords, pageTitle, enhancedTitle, type, references, breadcrumbs
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| Dementia With Lewy Bodies | e8e46d1d-46d2-4e5a-880f-f025a84c5871 |
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Brain | 3a0ceb4e-585c-4343-b8c3-30199a551c37 | 8e3dd335-218e-43f3-9635-d2a11eb0a445 | 8 | 08/10/20 | Dementia With Lewy Bodies | Brain, Diagnosis, Pathology-Based Diagnoses, Acquired Toxic/Metabolic/Degenerative Disorders, Dementias and Degenerative Disorders, Dementia With Lewy Bodies | Dementia With Lewy Bodies | STATdx | Dementia With Lewy Bodies | DX | true |
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title: "Dementia With Lewy Bodies" docid: "e8e46d1d-46d2-4e5a-880f-f025a84c5871" authors:
- key: "1fa14dfd-71ea-4960-908e-e720313bc63a" value: "Santhosh Gaddikeri, MD"
- key: "a25c450b-3d34-4f64-bba3-cc0834813df6" value: "Miral D. Jhaveri, MD, MBA" breadcrumbs:
- name: "Brain" slug: "brain" treeNodeId: "6d8829f1-14d7-45af-8675-255189aa526a"
- name: "Diagnosis" slug: "diagnosis" treeNodeId: "51c00394-446e-4a38-94af-d3b1d14d34e8"
- name: "Pathology-Based Diagnoses" slug: "pathology-based-diagnoses" treeNodeId: "d9d3a8ed-f21b-4831-8c77-591a3500ef77"
- name: "Acquired Toxic/Metabolic/Degenerative Disorders" slug: "acquired-toxicmetabolicdegenerativ-" treeNodeId: "ba3cfeaf-64d9-4117-91e8-d2ce58783fc5"
- name: "Dementias and Degenerative Disorders" slug: "dementias-and-degenerative-disorde-" treeNodeId: "6381104d-7a4c-4be5-bb19-3cd90837d547"
- name: "Dementia With Lewy Bodies" slug: "dementia-with-lewy-bodies" treeNodeId: null category: "Brain" cmeTopicId: "3a0ceb4e-585c-4343-b8c3-30199a551c37" documentVersionId: "8e3dd335-218e-43f3-9635-d2a11eb0a445" imageCount: 8 lastUpdated: "08/10/20" pageDescription: "Dementia With Lewy Bodies" pageKeywords: "Brain, Diagnosis, Pathology-Based Diagnoses, Acquired Toxic/Metabolic/Degenerative Disorders, Dementias and Degenerative Disorders, Dementia With Lewy Bodies" pageTitle: "Dementia With Lewy Bodies | STATdx" enhancedTitle: "Dementia With Lewy Bodies" type: "DX" references: true breadcrumbs:
- "Brain"
- "Diagnosis"
- "Pathology-Based Diagnoses"
- "Acquired Toxic/Metabolic/Degenerative Disorders"
- "Dementias and Degenerative Disorders"
- "Dementia With Lewy Bodies"
KEY FACTS
-
Terminology
- Progressive neurodegenerative dementia - Parkinsonism, visual hallucinations prominent - Caused by abnormal accumulation of α-synuclein protein
-
Imaging
- MR may differentiate Alzheimer disease (AD) from dementia with Lewy bodies (DLB)
- PET, SPECT most useful for DLB diagnosis
- Voxel-based morphometry - Relatively preserved hippocampal/medial temporal lobe volume in DLB vs. AD - ↓ volume of hypothalamus, substantia innominata, & putamen in DLB vs. AD
- FDG PET - ↓ in glucose metabolism in occipital cortex, especially primary visual cortex - F-18 fluorodopa-PET: ↓ striatal dopamine uptake in DLB vs. AD
- SPECT: Occipital lobe hypoperfusion, especially visual cortex
- 123 FP-CIT SPECT: ↓ uptake in striatum in DLB vs. AD
-
Top Differential Diagnoses
- Parkinson disease-associated dementia (PDD) - Similar clinical, pathological, imaging features with DLB
- AD
- Frontotemporal lobar degeneration (FTLD)
- Vascular dementia
-
Pathology
- Pathologic aggregation of α-synuclein protein in neurites (LB)
-
Diagnostic Checklist
- Unlike AD, medial temporal lobe atrophy not prominent feature
TERMINOLOGY
-
Abbreviations
- Dementia with Lewy bodies (DLB)
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Definitions
- Neurodegenerative dementia characterized by cognitive fluctuations, visual hallucinations, & motor parkinsonism - Caused by pathologic aggregation of α-synuclein protein in neurites (LB)
IMAGING
-
General Features
-
Best diagnostic clue
- MR may differentiate Alzheimer disease (AD) from DLB - PET, SPECT most useful for DLB diagnosis
-
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Imaging Recommendations
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Best imaging tool
- PET or SPECT
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-
MR Findings
-
T1WI
- Mild generalized atrophy -
T2WI
- Nonspecific white matter (WM) hyperintensities -
MRS
- ↓ WM NAA/Cr in DLB vs. healthy controls (HC) - ↑ Cho/Cr ratios in DLB vs. HC - Normal levels of NAA/Cr & myoinositol in DLB vs. AD -
Voxel-based morphometry - Relatively preserved hippocampal/medial temporal lobe volume in DLB vs. AD - ↓ volume of hypothalamus, substantia innominata, & putamen in DLB vs. AD - ↓ gray matter in temporal, parietal, & occipital regions vs. HC
-
DTI - ↑ mean diffusivity in amygdala - ↓ fractional anisotropy in pons & left thalamus vs. AD - ↓ fractional anisotropy in inferior longitudinal fasciculus & inferior occipitofrontal fasciculi vs. HC
-
-
Nuclear Medicine Findings
-
PET
- FDG PET: ↓ glucose metabolism in occipital cortex & visual association cortex with relative preservation of posterior cingulate - F-18 fluorodopa-PET: ↓ striatal dopamine uptake in DLB vs. AD -
MIBG scintigraphy
- ↓ myocardial uptake in DLB due to ↓ postganglionic sympathetic cardiac innervation -
SPECT - Occipital lobe hypoperfusion, especially visual cortex - 123 FP-CIT SPECT: Visualize DAT (dopamine transporter) loss - ↓ uptake in striatum in DLB
-
DIFFERENTIAL DIAGNOSIS
- Parkinson Disease-Associated Dementia
- Dementia typically develops at least 12 months after onset of initial parkinsonian symptoms
- Similar clinical, pathologic, imaging features to DLB
- Less pronounced atrophy in temporal, occipital, & parietal lobes vs. DLB
- Alzheimer Disease
- Parietal/temporal cortical atrophy - Disproportionate hippocampal volume loss
- Amyloid uptake of cerebral cortex in PiB-PET
- More severe, faster rate of progression than DLB
- Frontotemporal Lobar Degeneration
- Asymmetric frontal, anterior temporal lobar atrophy
- Behavioral variant: Both frontal lobes atrophic
- Semantic variant: Asymmetric anterior temporal lobe atrophy
- Vascular Dementia
- 2nd most common dementia (15-30%)
- WM & deep gray lacunae
- Infarcts of different ages
- Hyperintense lesions on T2WI, hypodense areas on CT, & focal atrophy suggestive of chronic infarcts
PATHOLOGY
-
General Features
-
Etiology
- Accumulation of α-synuclein protein (LB) - LB, neuronal loss in substantia nigra → dopamine depletion - Loss of cholinergic neurons in nucleus basalis of Meynert - → cognitive impairment, visual hallucinations -
Genetics
- Majority of DLB is sporadic; some are familial - α-synuclein gene mutation on chromosome 4 (*A53T*, *E46K* mutation) - Similar inheritance, similar genetic risk for PD - Other genes associated with DLB include *SNCA*, *APP*, *PSEN1*/*PSEN2*, *MAPT*, *GBA*, & *APOE*
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Staging, Grading, & Classification
- 3 major forms: Brainstem dominant, limbic/transitional, diffuse neocortical
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Gross Pathologic & Surgical Features
- Nonspecific & overlap with other neurodegenerative dementias
- Cortical atrophy is less than AD
- Atrophy affects frontal, temporal, & parietal lobes, relative sparing of occipital lobes
- Amygdala & cingulate gyri can show severe atrophy
-
Microscopic Features
- LB in substantia nigra, neocortex, limbic system - α-synuclein protein aggregates: Pale eosinophilic inclusions - α-synuclein - Physiologic function: Synaptic transmission, neuroprotective effect - Predominantly expressed in neurons
- Lewy neurites in hippocampus, amygdala, brainstem nuclei
- Neuronal loss in substantia nigra, locus ceruleus, nucleus basalis of Meynert, dorsal raphe nuclei - Relative preservation of cortical neurons
- Superficial microvacuolation of cerebral cortex, especially temporal cortex in severe cases
- 80% have associated AD-like pathology - Neuritic/diffuse plaques or neurofibrillary tangles
CLINICAL ISSUES
-
Presentation
-
Most common signs/symptoms
- Cognitive fluctuations, visual hallucinations, parkinsonism - Dysautonomia & sleep disorders -
Clinical criteria for DLB diagnosis - Core clinical features - Fluctuating cognition with pronounced variations in attention & alertness - Recurrent visual hallucinations (typically well formed & detailed) - REM sleep behavior disorder (May precede cognitive decline) - 1 or more spontaneous cardinal features of parkinsonism (bradykinesia, rest tremor, rigidity) - Supportive clinical features - Severe sensitivity to antipsychotic agents - Postural instability, repeated falls - Syncope or other transient episodes of unresponsiveness - Severe autonomic dysfunction (constipation, orthostatic hypotension, urinary incontinence) - Hypersomnia, hyposmia, hallucinations in other modalities, systematized delusions - Apathy, anxiety, & depression - Indicative biomarkers - ↓ dopamine transporter uptake in basal ganglia by SPECT or PET - Abnormal (low-uptake) I-123-MIBG myocardial scintigraphy - Polysomnographic confirmation of REM sleep without atonia - Supportive biomarkers - Relative preservation of medial temporal lobe structures on CT/MR - Generalized low uptake on SPECT/PET perfusion/metabolism scan with ↓ occipital activity ± cingulate island sign on FDG PET imaging - Prominent posterior slow-wave activity on EEG with periodic fluctuations in pre-alpha/theta range
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Probable DLB - ≥ 2 core clinical features of DLB with or without indicative biomarkers; or - Only 1 core clinical feature but with ≥ 1 indicative biomarkers - Probable DLB should not be diagnosed on basis of biomarkers alone
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Possible DLB - Only 1 core clinical feature of DLB with no indicative biomarker evidence; or - ≥ 1 indicative biomarkers but no core clinical features
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DLB is less likely - Presence of any other physical illness or brain disorder, including cerebrovascular disease, sufficient to account in part or in total for clinical picture - If parkinsonian features are only core clinical feature & appear for 1st time at stage of severe dementia
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Demographics
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Age
- 55-85 years; age is only risk factor - Average at presentation is 75 years -
Ethnicity
- LB formation more common in African Americans than Caucasians, but clinical diagnosis of DLB is not significantly different -
Sex
- M:F = 4:1 -
Epidemiology
- 5% of general population & 30% of dementia cases - 2nd most common neurodegenerative dementia (after AD) - Incidence rate of 0.1% per year in general population & 3.2% for new dementia cases
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Natural History & Prognosis
- Average survival after diagnosis < 8 years
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Treatment
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Options, risks, complications
- No disease-modifying treatments for DLB - Symptomatic, targeted toward specific disease manifestations - Cholinesterase inhibitor for cognitive features - DLB responds better to cholinesterase inhibitor than AD - Treatment against hallucination should be conservative due to neuroleptic hypersensitivity of DLB
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DIAGNOSTIC CHECKLIST
-
Image Interpretation Pearls
- No characteristic features on standard MR
- Clinical dementia + no/relatively mild medial temporal lobe atrophy - Unlike AD, medial temporal lobe atrophy is not prominent
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References
Selected References
- Colloby SJ et al: Cortical thinning in dementia with Lewy bodies and Parkinson disease dementia. Aust N Z J Psychiatry. 4867419885165, 2019
- Gupta V et al: Metabolic imaging patterns in posterior cortical atrophy and Lewy body dementia. Nucl Med Commun. 40(12):1275-82, 2019
- Yamada M et al: Diagnostic criteria for dementia with lewy bodies: updates and future directions. J Mov Disord. ePub, 2019
- Orimo S: [Differential diagnosis of dementia with lewy bodies.] Brain Nerve. 67(4):413-25, 2015
- Bertelson JA et al: Neuroimaging of dementia. Neurol Clin. 32(1):59-93, 2014
- Broski SM et al: Structural and functional imaging in parkinsonian syndromes. Radiographics. 34(5):1273-92, 2014
- Mak E et al: Neuroimaging characteristics of dementia with Lewy bodies. Alzheimers Res Ther. 6(2):18, 2014
- Peraza LR et al: fMRI resting state networks and their association with cognitive fluctuations in dementia with Lewy bodies. Neuroimage Clin. 4:558-65, 2014
- Bhogal P et al: The common dementias: a pictorial review. Eur Radiol. 23(12):3405-17, 2013
- Mortimer AM et al: Neuroimaging in dementia: a practical guide. Pract Neurol. 13(2):92-103, 2013
- Burton EJ et al: Medial temporal lobe atrophy on MRI differentiates Alzheimer's disease from dementia with Lewy bodies and vascular cognitive impairment: a prospective study with pathological verification of diagnosis. Brain. 132(Pt 1):195-203, 2009
- Ota M et al: Degeneration of dementia with Lewy bodies measured by diffusion tensor imaging. NMR Biomed. 22(3):280-4, 2009
- Watson R et al: Magnetic resonance imaging in lewy body dementias. Dement Geriatr Cogn Disord. 28(6):493-506, 2009
- Edison P et al: Amyloid load in Parkinson's disease dementia and Lewy body dementia measured with [11C]PIB positron emission tomography. J Neurol Neurosurg Psychiatry. 79(12):1331-8, 2008
- Perneczky R et al: Cerebral metabolic dysfunction in patients with dementia with Lewy bodies and visual hallucinations. Dement Geriatr Cogn Disord. 25(6):531-8, 2008
- Schmidt SL et al: Value of combining activated brain FDG-PET and cardiac MIBG for the differential diagnosis of dementia: differentiation of dementia with Lewy bodies and Alzheimer disease when the diagnoses based on clinical and neuroimaging criteria are difficult. Clin Nucl Med. 33(6):398-401, 2008
- McKeith I et al: Sensitivity and specificity of dopamine transporter imaging with 123I-FP-CIT SPECT in dementia with Lewy bodies: a phase III, multicentre study. Lancet Neurol. 6(4):305-13, 2007
- Seppi K et al: Dementia with Lewy bodies and Parkinson disease with dementia: can MRI make the difference? Neurology. 69(8):717-8, 2007
- Whitwell JL et al: Focal atrophy in dementia with Lewy bodies on MRI: a distinct pattern from Alzheimer's disease. Brain. 130(Pt 3):708-19, 2007
- Burton EJ et al: Progression of white matter hyperintensities in Alzheimer disease, dementia with lewy bodies, and Parkinson disease dementia: a comparison with normal aging. Am J Geriatr Psychiatry. 14(10):842-9, 2006
Images
Selected Images
Right & left medial sagittal FDG PET source & 3DSSP images of a 74-year-old man with dementia with Lewy bodies (DLB) presenting with visual hallucinations show severe ↓ metabolic activity in left visual cortex 
& precuneus 
. Note moderate ↓ metabolic activity in right occipital lobe 
& precuneus 
& relative sparing of bilateral posterior cingulate gyri 
.
Right & left medial sagittal FDG PET source & 3DSSP images of a 74-year-old man with dementia with Lewy bodies (DLB) presenting with visual hallucinations show severe ↓ metabolic activity in left visual cortex & precuneus . Note moderate ↓ metabolic activity in right occipital lobe & precuneus & relative sparing of bilateral posterior cingulate gyri .
Right & left medial sagittal FDG PET source & 3DSSP images of a 74-year-old man with dementia with Lewy bodies (DLB) presenting with visual hallucinations show severe ↓ metabolic activity in left visual cortex & precuneus . Note moderate ↓ metabolic activity in right occipital lobe & precuneus & relative sparing of bilateral posterior cingulate gyri .
Right & left medial sagittal FDG PET source & 3DSSP images of a 74-year-old man with dementia with Lewy bodies (DLB) presenting with visual hallucinations show severe ↓ metabolic activity in left visual cortex & precuneus . Note moderate ↓ metabolic activity in right occipital lobe & precuneus & relative sparing of bilateral posterior cingulate gyri .
Right & left medial sagittal FDG PET source & 3DSSP images of a 74-year-old man with dementia with Lewy bodies (DLB) presenting with visual hallucinations show severe ↓ metabolic activity in left visual cortex & precuneus . Note moderate ↓ metabolic activity in right occipital lobe & precuneus & relative sparing of bilateral posterior cingulate gyri .
Right & left medial sagittal FDG PET source & 3DSSP images of a 74-year-old man with dementia with Lewy bodies (DLB) presenting with visual hallucinations show severe ↓ metabolic activity in left visual cortex & precuneus . Note moderate ↓ metabolic activity in right occipital lobe & precuneus & relative sparing of bilateral posterior cingulate gyri .
Axial PET of the same patient shows preserved metabolism in frontal & temporal lobes. (Courtesy S Behnia, MD.)
Axial PET of the same patient shows preserved metabolism in frontal & temporal lobes. (Courtesy S Behnia, MD.)
Axial T2WI MR in a patient with DLB shows nonspecific diffuse cortical atrophy. Conventional MR findings are frequently nonspecific in DLB.
Axial T2WI MR in a patient with DLB shows nonspecific diffuse cortical atrophy. Conventional MR findings are frequently nonspecific in DLB.
123FP-CIT-SPECT, DAT imaging (dopamine transporter) shows normal symmetric uptake in the striatum of a healthy control (HC). In DLB, there is marked ↓ update in the putamen & mild in the caudate nuclei 
. Using DAT imaging, it is not possible to distinguish DLB from atypical parkinsonian syndromes like MSA, PSP, & CBD.
123FP-CIT-SPECT, DAT imaging (dopamine transporter) shows normal symmetric uptake in the striatum of a healthy control (HC). In DLB, there is marked ↓ update in the putamen & mild in the caudate nuclei . Using DAT imaging, it is not possible to distinguish DLB from atypical parkinsonian syndromes like MSA, PSP, & CBD.
Additional Images
Axial T2WI MR in a patient with cognitive decline, visual hallucination, & parkinsonism shows diffuse cortical atrophy consistent with DLB.
Axial T2WI MR in a patient with cognitive decline, visual hallucination, & parkinsonism shows diffuse cortical atrophy consistent with DLB.
Axial T2WI MR in the same patient exhibits mild atrophy of the medial temporal lobes.
Axial T2WI MR in the same patient exhibits mild atrophy of the medial temporal lobes.
Coronal T1WI MR in a patient with DLB shows prominent frontal lobe volume loss with relative sparing of hippocampal volume. (Courtesy M.J. Firbank, MD & J.T. O'Brien, MD.)
Coronal T1WI MR in a patient with DLB shows prominent frontal lobe volume loss with relative sparing of hippocampal volume. (Courtesy M.J. Firbank, MD & J.T. O'Brien, MD.)
Coronal T1WI MR in a patient with Alzheimer disease (AD) shows marked hippocampal volume loss & relative sparing of frontal lobes. (Courtesy M. J. Firbank, MD & J. T. O'Brien, MD.)
Coronal T1WI MR in a patient with Alzheimer disease (AD) shows marked hippocampal volume loss & relative sparing of frontal lobes. (Courtesy M. J. Firbank, MD & J. T. O'Brien, MD.)