Lewy Body Dementia (LBD)

Lewy Body Dementia/Disease (LBD) also known as Dementia with Lewy Bodies (DLB), is a neurodegenerative disorder associated with abnormal deposits of 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.

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

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

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.

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 (visuospatial) 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 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.

Rapid Eye Movement (REM) Sleep Behaviour Disorder is a sleep disorder characterized by repeated episodes of arousal, often associated with vocalizations and/or complex motor behaviours arising during REM sleep. Almost 90% of patients diagnosed with a REM sleep behaviour disorder will later develop a Parkinson's-plus disorder such as Parkinson's Disease (PD), Lewy Body Dementia (LBD), and Multiple System Atrophy.[2]

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.

    • 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[3]

Is It Lewy Body or Parkinsons's Disease Dementia?

Lewy Body Dementia presents with cognitive and/or psychiatric symptoms first, and is followed by the typical symptoms of Parkinson’s within 1 year (or from the very beginning). In Parkinson's Disease Dementia (PDD), the full motor symptoms of Parkinson’s need to be present for a minimum of 1 year, before the onset of cognitive impairment or dementia. PDD should be used to describe dementia that occurs in the context of already well-established Parkinson's disease. In research studies where a distinction needs to be made between LBD and PDD, the “1-year rule” between the onset of dementia and parkinsonism is commonly used.[4]
  • 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 processing speed and divided/alternating attention (e.g. - Stroop test, trail-making tasks, phonemic fluency, and computerized tasks of reaction time) can be helpful to reveal disproportionate deficits in these areas
  • The spatial and perceptual difficulties of DLB often occur early
    • Commonly see in 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.

A diagnostically suggestive feature is low striatal dopamine transporter uptake on Single-Photon Emission Computed Tomography (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.

On MRI, generalized atrophy can be seen in most dementias. However, for LBD, the relative sparing of the medial temporal lobes is suggestive of LBD.[5]

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

Typical antipsychotics are contraindicated in LBD and Parkinsons's

A severe sensitivity reaction occurs in an estimated 25-50% of LBD and Parkinsons's patients administered typical antipsychotic drugs (especially haloperidol) in the usual dose range.[6] 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.[7]

Acetylcholinesterase inhibitors should usually be the first drugs used to treat hallucinations and agitation in patients with LBD. Both rivastigmine and donepezil are effective in DLB for improving cognition, global function, and activities of living.[8][9] 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.[10]

Motor symptoms can be treated with low doses of carbidopa-levodopa.

Low-dose clonazepam can be used to treat REM sleep behaviour disorder. There are no systematic studies of antidepressants for depression in DLB.

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