Dementia with Lewy bodies
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| Dementia with Lewy bodies | |
| ICD-10 | G31.8 |
|---|---|
| ICD-9 | 331.82 |
| DiseasesDB | 3800 |
| MeSH | D020961 |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Kiran Singh, M.D. [2]
Overview
Dementia with Lewy bodies is the second most frequent cause of hospitalization for dementia, after Alzheimer's disease. Current estimates are that about 60-to-75% of diagnosed dementias are of the Alzheimer's and mixed (Alzheimer's and vascular dementia) type, 10-to-15% are Lewy Bodies type, with the remaining types being of an entire spectrum of dementias including frontotemporal lobar degeneration, alcoholic dementia, pure vascular dementia, etc.
Historical Perspective
- Lewy body dementia (LBD) was named after Frederich Heinrich Lewy, a German-American neurologist who discovered the characteristic intracytoplasmic inclusions in 1912.[1][2]
- In 1961, Okazaki suggested that the presence of cortical Lewy bodies with associated with the development of dementia.[1]
- In 1984, Kosaka and colleagues hypothesized that the presence of Lewy bodies may correspond to a new disease entity, which was eventually named "diffuse Lewy body disease".[3] The disease name was then changed in 1996 at the First International Workshop of the Consortium on Dementia with Lewy Bodies (DLB) to become "dementia with Lewy bodies".[4]
- DLB was not considered a diagnosis of dementia in the first 4 versions of the Diagnostic and Statistical Manual (DSM) for Mental Disorders. In 2013, DSM-5 finally incorporated DLB as a diagnosis for dementia.[5][2]
Presentation
Dementia with Lewy Bodies (DLB) exhibits clinical overlap between Alzheimer's disease and Parkinson's disease. Pathologically, it is characterized by development of abnormal proteinaceous (alpha-synuclein) cytoplasmic inclusions, called Lewy bodies, throughout the brain. These inclusions have similar structural features to "classical" Lewy Bodies seen subcortically in Parkinson's disease.
Additionally, there is a loss of dopamine-producing neurons (in the substantia nigra) similar to that seen in Parkinson's disease, and a loss of acetylcholine-producing neurons (in the basal nucleus of Meynert and elsewhere) similar to that seen in Alzheimer's disease. Cerebral atrophy (or shrinkage) also occurs as the cerebral cortex degenerates. Autopsy series have revealed that the pathology of DLB is often concomitant with the pathology of Alzheimer's disease. That is, when Lewy Body inclusions are found in the cortex, they often co-occur with Alzheimer's disease pathology found primarily in the hippocampus, including: neurofibrillary tangles (abnormally phosphorylated tau protein), senile plaques (deposited beta-amyloid protein), and granulovacuolar degeneration.
Within DLB, the loss of cholinergic (acetylcholine-producing) neurons is thought to account for the degradation of cognitive and emotional functioning as in Alzheimer's disease, while the loss of dopaminergic (dopamine-producing) neurons is thought to account for the degradation of motor control as in Parkinson's disease. Thus, DLB is similar in some ways to both the dementia resulting from Alzheimer's disease and Parkinson's disease. In fact, it is often confused in its early stages with Alzheimer's disease and/or vascular dementia (multi-infarct dementia). The overlap of neuropathologies and presenting symptoms (cognitive, emotional, and motor) may make an accurate differential diagnosis difficult to reach.
Differential Diagnosis
Dementia with Lewy bodies (DLB) should be distinguished from other disorder that cause memory impairment, recurrent hallucinations, and Parkinsonism. The most important differential diagnosis of DLB are Alzheimer's disease (AD) and Parkinson's disease (PD) due to the overlapping features of the 3 diseases and absence of clinical, radiographic, or neuropathological features that distinguish one from the other.
Alzheimer's disease (AD)
- The majority of patients with LBD have senile and neuritic plaques suggestive of AD.[6]
- Patients with AD have more prominent memory deficits.
- Patients with DLB generally meet the criteria for the diagnosis of AD.
- Patients with DLB often have a more rapid course of memory impairment than do patients with AD.[6]
- Greater atrophy is generally observed in the grey matter medial temporal lobe among patients with AD compared to atrophy observed in putamen, basal forebrain, and white matter among patients with DLB.[6]
Parkinson's disease (PD) and Parkinson's disease dementia (PDD)
- PD characterized by bradykinesia, resting tremor, cogwheel rigidity.[6][7]
- More than 80% of patients diagnosed with PD develop dementia.[7]
- PD, PDD, and DLB have all been proposed to represent various ends of the spectrum of the same disease.[6][7]
- Many patients with PD eventually develop dementia.
- In contrast to PD and PDD, parkinsonism in DLB occurs before or at 1 year following onset of dementia symptoms. Patients with DLB classically present with earlier onset of falls and bone fractures compared to those with PD.[7]
- Imaging is generally not useful to differentiate between PD and DLB. Cortical and subcortical Lewy bodies may be present in PD and DLB.[8]
- Patients with DLB are less likely to respond to antiparkinsonian and antipsychotic pharmacotherapy. Paradoxically, DLB patients administered antiparkinsonian drugs have worse psychotic symptoms, and DLB patients administered antipsychotic drugs have increased rigidity, bradykinesia, and autonomic dysfunction (eg. orthostatic hypotension).[9]
Other Neurodegenerative Disorders
Other neurodegenerative disorders may also be considered in the differential diagnosis of DLB[6]:
- Parkinson-plus syndromes (such as progressive supranuclear palsy, corticobasal degeneration, and multiple system atrophy)
- Cortical basal ganglionic degeneration
- Frontotemporal dementia (FTD)
- Hydrocephalus
- Vascular dementia
- Prion-associated neurodegenerative diseases (eg. Creutzfeldt-Jakob disease)
Epidemiology and Demographics
DLB is the 2nd most common cause of dementia after Alzheimer's disease (AD) and is the underlying etiology of approximately 1.7-30.5% of dementia cases. DLB generally affects elderly patients > 65 years of age, and it has no gender predilection.
Incidence
- In the general population, the annual incidence of DLB is 100 per 100,000 persons.[10]
- Among patients with dementia, the annual incidence of DLB is 3,200 - 5,000 per 100,000 persons.[10]
Prevalence
- In the general population, the prevalence of DLB is approximately 5,000 per 100,000 persons.[11][12][13][14][15][16]
- Among patients with dementia, the prevalence of DLB ranged between 1,700 to 30,500 per 100,000 persons.[11][12][13][14][15][16]
Age
- The majority of patients diagnosed with DLB are elderly patients aged > 65 yeas.
Gender
- DLB has no gender predilection
Risk Factors
- Genetic predisposition[17]
Diagnosis
Clinical features
Core features include fluctuating cognition with variations in attention and alertness, recurrent visual hallucinations (typically early in the disease), and motor features of parkinsonism. DLB patients also often experience repeated falls, syncope (fainting), transient loss of consciousness, and hypersentivity to neuroleptic medications. Generally, DLB is diagnosed when cognitive symptoms develop within a year or two of movement disorder/Parkinsonian symptoms. Recent research suggests that presence of sleep disturbance may also be useful in differentiating DLB from other forms of dementia.
Diagnostic Criteria
DSM-V Diagnostic Criteria for Major or Mild Neurocognitive Disorder With Lewy Bodies[17]
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For probable major or mild neurocognitive disorder with Lewy bodies, the individual has two core features, or one suggestive feature with one or more core features. For possible major or mild neurocognitive disorder with Lewy bodies, the individual has only one core feature, or one or more suggestive features.
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Treatment
The treatment of DLB, as with Parkinson's disease, involves striking a balance between treating the motor and emotive/cognitive symptoms. Treatment of the movement portion of the disease can typically result in worsening hallucinations and psychosis, while treatment of the hallucinations and psychosis can result in worsening movement symptoms. The use of cholinesterase inhibitors represents the treatment of choice. This improves symptoms, but does not cure the disease. The use of memantine may be recommended, and may represent a means to slow or prevent the decline of cognitive function, although strong evidence to support or disprove this is lacking.
Nomenclature
Dementia with Lewy bodies (DLB) is also known under a variety of other names including, Lewy Body dementia (LBD), Diffuse Lewy Body disease (DLBD), Cortical Lewy Body disease (CLBD), and Senile dementia of Lewy type. All incorporate the name Lewy, as Dr. Frederic Lewy (1885-1950) was first to discover the abnormal protein deposits ("Lewy Body inclusions") in the early 1900s.[18][19]
References
- ↑ 1.0 1.1 OKAZAKI H, LIPKIN LE, ARONSON SM (1961). "Diffuse intracytoplasmic ganglionic inclusions (Lewy type) associated with progressive dementia and quadriparesis in flexion". J Neuropathol Exp Neurol. 20: 237–44. PMID 13730588.
- ↑ 2.0 2.1 Huang Y, Halliday G (2013). "Can we clinically diagnose dementia with Lewy bodies yet?". Transl Neurodegener. 2 (1): 4. doi:10.1186/2047-9158-2-4. PMC 3575256. PMID 23398715.
- ↑ Kosaka K, Yoshimura M, Ikeda K, Budka H (1984). "Diffuse type of Lewy body disease: progressive dementia with abundant cortical Lewy bodies and senile changes of varying degree--a new disease?". Clin Neuropathol. 3 (5): 185–92. PMID 6094067.
- ↑ McKeith IG, Galasko D, Kosaka K, Perry EK, Dickson DW, Hansen LA; et al. (1996). "Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB international workshop". Neurology. 47 (5): 1113–24. PMID 8909416.
- ↑ Regier DA, Kuhl EA, Kupfer DJ (2013). "The DSM-5: Classification and criteria changes". World Psychiatry. 12 (2): 92–8. doi:10.1002/wps.20050. PMC 3683251. PMID 23737408.
- ↑ 6.0 6.1 6.2 6.3 6.4 6.5 Morra LF, Donovick PJ (2014). "Clinical presentation and differential diagnosis of dementia with Lewy bodies: a review". Int J Geriatr Psychiatry. 29 (6): 569–76. doi:10.1002/gps.4039. PMID 24150834.
- ↑ 7.0 7.1 7.2 7.3 Aarsland D, Litvan I, Salmon D, Galasko D, Wentzel-Larsen T, Larsen JP (2003). "Performance on the dementia rating scale in Parkinson's disease with dementia and dementia with Lewy bodies: comparison with progressive supranuclear palsy and Alzheimer's disease". J Neurol Neurosurg Psychiatry. 74 (9): 1215–20. PMC 1738667. PMID 12933921.
- ↑ Vernon AC, Ballard C, Modo M (2010). "Neuroimaging for Lewy body disease: is the in vivo molecular imaging of α-synuclein neuropathology required and feasible?". Brain Res Rev. 65 (1): 28–55. doi:10.1016/j.brainresrev.2010.05.006. PMID 20685363.
- ↑ Molloy S, McKeith IG, O'Brien JT, Burn DJ (2005). "The role of levodopa in the management of dementia with Lewy bodies". J Neurol Neurosurg Psychiatry. 76 (9): 1200–3. doi:10.1136/jnnp.2004.052332. PMC 1739807. PMID 16107351.
- ↑ 10.0 10.1 Miech RA, Breitner JC, Zandi PP, Khachaturian AS, Anthony JC, Mayer L (2002). "Incidence of AD may decline in the early 90s for men, later for women: The Cache County study". Neurology. 58 (2): 209–18. PMID 11805246.
- ↑ 11.0 11.1 de Silva HA, Gunatilake SB, Smith AD (2003). "Prevalence of dementia in a semi-urban population in Sri Lanka: report from a regional survey". Int J Geriatr Psychiatry. 18 (8): 711–5. doi:10.1002/gps.909. PMID 12891639.
- ↑ 12.0 12.1 Herrera E, Caramelli P, Silveira AS, Nitrini R (2002). "Epidemiologic survey of dementia in a community-dwelling Brazilian population". Alzheimer Dis Assoc Disord. 16 (2): 103–8. PMID 12040305.
- ↑ 13.0 13.1 Rahkonen T, Eloniemi-Sulkava U, Rissanen S, Vatanen A, Viramo P, Sulkava R (2003). "Dementia with Lewy bodies according to the consensus criteria in a general population aged 75 years or older". J Neurol Neurosurg Psychiatry. 74 (6): 720–4. PMC 1738491. PMID 12754338.
- ↑ 14.0 14.1 Stevens T, Livingston G, Kitchen G, Manela M, Walker Z, Katona C (2002). "Islington study of dementia subtypes in the community". Br J Psychiatry. 180: 270–6. PMID 11872521.
- ↑ 15.0 15.1 Yamada T, Hattori H, Miura A, Tanabe M, Yamori Y (2001). "Prevalence of Alzheimer's disease, vascular dementia and dementia with Lewy bodies in a Japanese population". Psychiatry Clin Neurosci. 55 (1): 21–5. doi:10.1046/j.1440-1819.2001.00779.x. PMID 11235852.
- ↑ 16.0 16.1 Yamada T, Kadekaru H, Matsumoto S, Inada H, Tanabe M, Moriguchi EH; et al. (2002). "Prevalence of dementia in the older Japanese-Brazilian population". Psychiatry Clin Neurosci. 56 (1): 71–5. doi:10.1046/j.1440-1819.2002.00931.x. PMID 11929573.
- ↑ 17.0 17.1 Diagnostic and statistical manual of mental disorders : DSM-5. Washington, D.C: American Psychiatric Association. 2013. ISBN 0890425558.
- ↑ http://www.rudramani.com/alzh.html/
- ↑ Template:WhoNamedIt
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