Lewy Body Dementia (LBD)

Primer

Lewy Body Dementia/Disease (LBD) also known as Dementia with Lewy Bodies (DLB), is a neurodegenerative disorder associated with abnormal deposits of a protein called alpha-synuclein in the brain. It is characterized by progressive cognitive impairment (with early changes in complex attention and executive function rather than learning and memory), recurrent complex visual hallucinations, rapid eye movement (REM) sleep behavior disorder, depression, and/or delusions. LBD is one of the most common causes of dementia.

Diagnostic Criteria

Criterion A

The criteria are met for major or mild neurocognitive disorder.

Criterion B

The disorder has an insidious onset and gradual progression.

Criterion C

The disorder meets a combination of core diagnostic features and suggestive diagnostic features for either probable or possible neurocognitive disorder with Lewy bodies.

For probable major or mild neurocognitive disorder with Lewy bodies, the individual has 2 core features, or 1 suggestive feature with 1 or more core features.

For possible major or mild neurocognitive disorder with Lewy bodies, the individual has only 1 core feature, or 1 or more suggestive features.

  1. Core diagnostic features:
    • a. Fluctuating cognition with pronounced variations in attention and alertness
    • b. Recurrent visual hallucinations that are well formed and detailed
    • c. Spontaneous features of parkinsonism, with onset subsequent to the development of cognitive decline
  2. Suggestive diagnostic features:
    • a. Meets criteria for rapid eye movement sleep behaviour disorder
    • b. Severe neuroleptic sensitivity
Criterion D

The disturbance is not better explained by cerebrovascular disease, another neurodegenerative disease, the effects of a substance, or another mental, neurological, or systemic disorder.

Specifiers

Specifiers

Specify if:

  • Probable major neurocognitive disorder with Lewy bodies
    • With behavioral disturbance
    • Without behavioral disturbance
  • Possible major neurocognitive disorder with Lewy bodies
  • Mild neurocognitive disorder with Lewy bodies

2017 Consensus Criteria

The diagnostic criteria for lewy body dementia continues to evolve, and while the DSM-5 provides a guiding diagnostic framework, it was published in 2013, and many new research findings have occurred. The latest consensus is from the Fourth consensus report of the DLB Consortium, issued in 2017.[1] The diagnostic criteria contains categories of probable and possible DLB, describing the clinical presentations most typical of dementia associated with underlying Lewy-related pathology.

Clinical Features

Revised Criteria for the Clinical Diagnosis of Probable and Possible Dementia with Lewy bodies (DLB)

McKeith, I. G. et al (2017). Diagnosis and management of dementia with Lewy bodies: Fourth consensus report. Neurology, 89(1), 88-100
Essential Essential for a diagnosis of DLB is dementia, defined as a progressive cognitive decline of sufficient magnitude to interfere with normal social or occupational functions, or with usual daily activities. Prominent or persistent memory impairment may not necessarily occur in the early stages but is usually evident with progression. Deficits on tests of attention, executive function, and visuoperceptual ability may be especially prominent and occur early.
Core clinical features (The first 3 typically occur early and may persist throughout the course.)
1. Fluctuating cognition with pronounced variations in attention and alertness.
2. Recurrent visual hallucinations that are typically well formed and detailed.
3. REM sleep behavior disorder, which may precede cognitive decline.
4. 1 or more spontaneous cardinal features of parkinsonism: these are bradykinesia (defined as slowness of movement and decrement in amplitude or speed), rest tremor, or rigidity.
Supportive clinical features Severe sensitivity to antipsychotic agents; postural instability; repeated falls; syncope or other transient episodes of unresponsiveness; severe autonomic dysfunction, e.g., constipation, orthostatic hypotension, urinary incontinence; hypersomnia; hyposmia; hallucinations in other modalities; systematized delusions; apathy, anxiety, and depression.
Indicative biomarkers • Reduced dopamine transporter uptake in basal ganglia demonstrated by SPECT or PET.
• Abnormal (low uptake) 123iodine-MIBG myocardial scintigraphy.
• Polysomnographic confirmation of REM sleep without atonia.
Supportive biomarkers • Relative preservation of medial temporal lobe structures on CT/MRI scan.
• Generalized low uptake on SPECT/PET perfusion/metabolism scan with reduced occipital activity 6 the cingulate island sign on FDG-PET imaging.
• Prominent posterior slow-wave activity on EEG with periodic fluctuations in the pre-alpha/ theta range.

Probable vs. Possible Diagnosis

Probable versus Possible Diagnosis

Probable DLB can be diagnosed if:
a. 2 or more core clinical features of DLB are present, with or without the presence of indicative biomarkers, or

b. Only 1 core clinical feature is present, but with 1 or more indicative biomarkers.
(Probable DLB should not be diagnosed on the basis of biomarkers alone.)
Possible DLB can be diagnosed if:
a. Only 1 core clinical feature of DLB is present, with no indicative biomarker evidence, or

b. 1 or more indicative biomarkers is present but there are no core clinical features.
DLB is less likely:
a. In the presence of any other physical illness or brain disorder including cerebrovascular disease, sufficient to account in part or in total for the clinical picture, although these do not exclude a DLB diagnosis and may serve to indicate mixed or multiple pathologies contributing to the clinical presentation, or

b. If parkinsonian features are the only core clinical feature and appear for the first time at a stage of severe dementia.

Pathophysiology

The underlying pathophysiology of LBD is primarily a synucleinopathy due to alpha-synuclein misfolding and aggregation. Lewy body pathology frequently coexists with Alzheimer's disease and cerebrovascular disease pathology, particularly among the oldest age groups. In Alzheimer's disease, there is concomitant synuclein pathology in 60% of cases.

Differential Diagnosis

  • Parkinsons's Disease Dementia (PDD)
  • Alzhiemer's Disease
    • Because of considerable pathologic heterogeneity, some dementia presentations associated with Lewy-related pathology are atypical. For example, if abundant neocortical neuritic plaques and tangles are present in addition to Lewy bodies, the clinical profile may more closely resemble AD rather than DLB. Such mixed pathology cases are common, explaining why up to half of carefully research-diagnosed patients with AD may have unsuspected Lewy-related pathology at autopsy.
  • Depression with psychotic features[2]

Lewy Body or Parkinsons's?

Is It Lewy Body or Parkinsons's?

LBD patients present with memory impairments first, where as PD patients present with motor impairments first. LBD should also be diagnosed when dementia occurs before or concurrently with parkinsonism. The term Parkinson disease dementia (PDD) should be used to describe dementia that occurs in the context of well-established Parkinson disease. In a clinical setting the term that is most appropriate to the clinical situation should be used and generic terms such as Lewy Body Disease are often helpful. In research studies in which distinction needs to be made between LBD and PDD, the existing 1-year rule between the onset of dementia and parkinsonism continues to be recommended.

Investigations

Cognitive Testing

  • Cognitive tests like the Mini-Mental Status Exam (MMSE) and Montreal Cognitive Assessment (MoCA) are useful to characterize global impairment. Deficits are typically in attention, executive function, and visual processing
  • Measures of attention/executive function that differentiate DLB from AD and normal aging and that predict progression from mild cognitive impairment (MCI) to DLB include tests of processing speed and divided/alternating attention (e.g. - Stroop test, trail-making tasks, phonemic fluency, and computerized tasks of reaction time)
  • The spatial and perceptual difficulties of DLB often occur early; including tasks of figure copying (e.g. - intersecting pentagons, complex figure copy; visual assembly, block design, puzzle tasks; spatial matching, line orientation, size matching tasks; and perceptual discrimination)
  • Memory and object naming tend to be less affected in DLB, and are best evaluated through story recall, verbal list learning, and confrontation naming tasks, although some patients' difficulties may be secondary to speed or retrieval task demands.

Neuroimaging

A diagnostically suggestive feature is low striatal dopamine transporter uptake on spect or positron emission tomography (PET) scan. See also: Surendranathan, A., & O’brien, J. T. (2018). Clinical imaging in dementia with Lewy bodies. Evidence-based mental health, 21(2), 61-65.

Antipsychotics

Neuroleptic sensitivity is not a diagnostic marker but does raises suspicion of LBD if it does occur. However, this is not a diagnostic approach.

Treatment

Pharmacotherapy

Typical antipsychotics are contraindicated in LBD

A severe sensitivity reaction occurs in an estimated 25-50% of LBD patients administered typical antipsychotic drugs (especially haloperidol) in the usual dose range.[3] This results in cognitive impairment, sedation, increased/irreversible acute onset of parkinsonism, or symptoms resembling neuroleptic malignant syndrome. If an antipsychotic must be used, then low potency atypical antipsychotics like clozapine or quetiapine should be used.[4]

Acetylcholinesterase inhibitors, both rivastigmine or donepezil are effective in DLB for improving cognition, global function, and activities of living.[5][6] Furthermore, if patients do not improve with treatment, there is a lower likelihood of deterioration. There is less evidence for the efficacy of memantine, but it is well-tolerated and may have benefits, either as monotherapy or as an adjunctive to a acetylcholinesterase inhibitors.[7]

Resources

For Patients
Case Reports

References

1) McKeith, I. G., Boeve, B. F., Dickson, D. W., Halliday, G., Taylor, J. P., Weintraub, D., ... & Bayston, A. (2017). Diagnosis and management of dementia with Lewy bodies: Fourth consensus report of the DLB Consortium. Neurology, 89(1), 88-100.
2) Perera, J. K., Rosenblat, J. D., & Flint, A. J. (2017). Dementia with Lewy bodies presenting as psychotic depression. Australian & New Zealand Journal of Psychiatry, 51(11), 1160-1161.
3) Boot, B. P., McDade, E. M., McGinnis, S. M., & Boeve, B. F. (2013). Treatment of dementia with Lewy bodies. Current treatment options in neurology, 15(6), 738-764.
4) Lewy Body Dementia Association: Emergency Room Treatment of Psychosis
5) O’Brien, J. T., Holmes, C., Jones, M., Jones, R., Livingston, G., McKeith, I., ... & Sampson, E. L. (2017). Clinical practice with anti-dementia drugs: a revised (third) consensus statement from the British Association for Psychopharmacology. Journal of Psychopharmacology, 31(2), 147-168.
6) Mori, E., Ikeda, M., Nagai, R., Matsuo, K., Nakagawa, M., & Kosaka, K. (2015). Long-term donepezil use for dementia with Lewy bodies: results from an open-label extension of Phase III trial. Alzheimer's research & therapy, 7(1), 5.
7) Wesnes, K. A., Aarsland, D., Ballard, C., & Londos, E. (2015). Memantine improves attention and episodic memory in Parkinson's disease dementia and dementia with Lewy bodies. International journal of geriatric psychiatry, 30(1), 46-54.