Dementia with Lewy bodies

Diagnosis

Diagnostic criteria (McKeith 1) Core clinical criteria (McKeith et al, 2017)

a. A progressive cognitive decline of sufficient magnitude to interfere with functional independence

b. Prominent or persistent memory impairment may not necessarily occur in the early stages, but is usually evident with progression

c. Deficits in attention, executive function, and visuoperceptual ability may be especially prominent and occur early

2) Core clinical features (A through C typically occur early and may persist throughout course)

a. Fluctuating cognition and pronounced variations in attention and alertness

b. Recurrent visual hallucinations that are typically well formed and detailed (classically they are of children or animals and are typically silent; illusions are common especially in poor lighting) (Salardini 2019) (these are likely influenced by visuoperceptual processing deficits) (Mori 2000)

c. REM sleep behavior disorder, which may precede cognitive decline

d. One or more spontaneous cardinal features of Parkinsonism:

i. Bradykinesia (defined as slowness of movement and decrement in amplitude or speed)

ii. Rest tremor

iii. Rigidity

3) Supportive clinical features:

a. Severe sensitivity to antipsychotic agents

b. Postural instability

c. Repeated falls

d. Syncope or other transient episodes of unresponsiveness

e. Severe autonomic dysfunction (e.g., constipation, orthostatic hypotension, urinary incontinence)

f. Hypersomnia

g. Hyposmia

h. Hallucinations in other modalities

i. Systematized delusions (i.e. delusional misidentification, possibly related to defective visual perceptions) (Mori 2000)

j. Apathy

k. Anxiety

l. Depression

4) Indicative biomarkers

a. Reduced dopamine transporter uptake in basal ganglia demonstrated by SPECT or PET

b. Abnormal (low uptake) 123I MIBG myocardial scintography (this quantifies postganglionic sympathetic cardiac innervation which is reduced in Lewy-body dementia).

i. Must be interpreted with caution in patients with heart failure, ischemic heart disease, diabetes, peripheral neuropathy, and medications that interfere with the test including labetalol, TCAs, and over-the-counter sympathomimetics

c. Polysomnographic confirmation of REM sleep without atonia

5) Supportive biomarkers

a. Relative preservation of medial temporal lobe structures on CT/MRI

b. Generalized low uptake on SPECT/PET perfusion/metabolism scan with reduced occipital activity +/- the cingulate island sign on FDG-PET imaging

c. Prominent posterior slow-wave activity on EEG with periodic fluctuations in the pre-alpha/theta range

6) Probable DLB can be diagnosed if:

a. Two or more core clinical features of DLB are present, with or without the presence of indicative biomarkers, or

b. Only one core clinical features is present, but with one or more indicative biomarkers

c. Cannot be diagnosed on the basis of biomarkers alone

7) Possible DLB can be diagnosed if:

a. Only one core clinical feature of DLB is present, with no indicative biomarker evidence, or

b. One or more indicative biomarkers is present, but there are no core clinical features.

8) 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 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.

9) DLB should be diagnosed with dementia occurs before or concurrently with parkinsonism. Parkinson disease dementia should be used to describe dementia that occurs in the context of well-established Parkinson disease.

Imaging

(Salardini 2019)

- FDG-PET (A) demonstrates occipital hypometabolism

- DAT-SPECT (B) shows loss of dopaminergic innervation in striatum (superimposed lighter signal is dopamine transporter uptake signal)

Management

• Pharmacologic
  • Acetylcholinesterase inhibitors (donepezil and rivastigmine) are used for improvement in cognition, global functioning – even if they do not improve, it is likely to slow deterioration (McKeith et al, 2017)
    • Rivastigmine (but not donepezil) was associated with greater risk of adverse events; there is limited evidence to support galantamine (Stinton et al, 2015)
  • Memantine efficacy is unclear, but it’s generally well tolerated (McKeith et al, 2017)
• Nonpharmacologic: relatively few studies with small sample sizes and poor research quality, no firm treatment recommendations 101
  • Likely interventions such as physical activity, occupational therapy, music therapy, as well as caregiver education and support, which have effectiveness in other dementias, would prove similarly helpful in LBD (Connors et al, 2018)
  • Based on experience in the clinic, the visual hallucinations do seem to often be associated with loneliness, and patients have benefited from more time spent with their loved ones or pets
• Neuropsychiatric symptoms
  • Acetylcholinesterase inhibitors are helpful in reduction of apathy and visual hallucinations (which may in turn reduce anxiety and agitation driven by psychosis) (Connors et al, 2018)
  • Avoid antipsychotics whenever possible due to sensitivity to neuroleptics. Olanzapine and quetiapine seem to be limited by adverse effects (Stinton et al, 2015). There is limited evidence for clozapine and risperidone is not beneficial (Stinton et al, 2015). If needed, low-dose quetiapine may be relatively safer (McKeith et al, 2017)
  • Citalopram does not appear to be beneficial (Stinton et al, 2015) There is limited evidence for duloxetine, escitalopram, and trazodone (Stinton et al 2015)

References

Connors, M. H. et al. Non-pharmacological interventions for Lewy body dementia: a systematic review. Psychol. Med. 48, 1749–1758 (2018). PubMed link

McKeith, I. G. et al. Diagnosis and management of dementia with Lewy bodies: Fourth consensus report of the DLB Consortium. Neurology 89, 88–100 (2017). PubMed link

Mori, E. et al. Visuoperceptual Impairment in Dementia With Lewy Bodies. Arch. Neurol. 57, 489 (2000). PubMed link

Salardini, A. An Overview of Primary Dementias as Clinicopathological Entities. Semin. Neurol. 39, 153–166 (2019). PubMed link

Stinton, C. et al. Pharmacological Management of Lewy Body Dementia: A Systematic Review and Meta-Analysis. Am. J. Psychiatry 172, 731–742 (2015). PubMed link