Dementia with Lewy Bodies (Including Parkinson’s Disease Dementia)

A 65-year-old man came to the clinic complaining of cognitive difficulties. He had been forgetful for about a year, often confused, and was unable to use the television remote. When asked what his biggest problem was he complained of trouble seeing, stating that “no one can get my eyeglasses prescription correct,” despite the fact that he had been to multiple optometrists. He had less volume in his voice, less expression in his face, and his walking had slowed down. On review of systems he admitted to having visual hallucinations of people and animals—which he did not mention for fear of being considered crazy. On exam he had masked facies, increased tone, cogwheeling, and a shuffling gait.

Quick Start

Definition	• Dementia with Lewy bodies is a neurodegenerative disease of the brain characterized clinically by dementia, visual hallucinations, Parkinsonism, and rapid eye movement (REM) sleep behavior disorder, and characterized pathologically by Lewy body formation and abnormal alpha-synuclein metabolism. • Parkinson’s disease dementia is a term used for dementia with Lewy bodies when extrapyramidal motor features are present for more than a year prior to the onset of dementia.
Prevalence	• Autopsy studies have suggested that dementia with Lewy bodies accounts for up to 20% of cases of dementia, either by itself or in combination with other disorders.
Genetic risk	• There are familial cases of dementia with Lewy bodies related to mutations or repeats of the alpha-synuclein gene located on chromosome 4. Most patients with dementia with Lewy bodies, however, do not show abnormalities of this gene.
Cognitive and other symptoms	• Impairment in attention, executive function, and visuospatial ability are often prominent. Memory impairment may or may not be prominent initially. • In patients who also have Alzheimer’s pathology, memory and word-finding deficits are prominent as well. • Sleep disturbances are common in dementia with Lewy bodies, leading to disrupted circadian rhythm, fluctuating levels of attention and alertness, and REM sleep behavior disorder.
Diagnostic criteria	1. Essential for a diagnosis is dementia. 2. Core features (two are sufficient) include: a. Fluctuating cognition (pronounced variations in attention and alertness) b. Visual hallucinations (recurrent, well formed, detailed, of people and/or animals, often initially present around transitions between sleep and wake) c. Spontaneous features of Parkinsonism (i.e., Parkinsonism not related to medications). 3. Suggestive features (probable: one or more plus one core feature; possible one or more without any core features): a. REM sleep behavior disorder b. Severe neuroleptic sensitivity c. Low dopamine transporter uptake in basal ganglia demonstrated by SPECT or PET imaging.
Behavioral symptoms	• Changes in behavior include visual hallucinations (which may or may not be frightening) and fluctuations in attention and alertness.
Treatment	• Cholinesterase inhibitors have been found to be beneficial; one has been approved by the US Food and Drug Administration. • Other medications, including levodopa/carbidopa (Sinemet), memantine, selective serotonin reuptake inhibitors (SSRIs), and atypical antipsychotics, may be used with caution.
Top differential diagnoses	• Most common: Alzheimer’s disease and mixed dementia (dementia with Lewy bodies plus Alzheimer’s disease). • Less common: vascular dementia and atypical Parkinsonian syndromes including corticobasal degeneration and progressive supranuclear palsy.

Prevalence, Prognosis, and Definition

Dementia with Lewy bodies is a neurodegenerative disease of the brain characterized clinically by dementia, visual hallucinations, and/or Parkinsonism, and characterized pathologically by Lewy body formation and abnormal alpha-synuclein metabolism. Rapid eye movement (REM) sleep behavior disorder is also very common. Parkinson’s disease dementia (PDD), diagnosed when extrapyramidal motor features are present for more than a year prior to the onset of dementia, is recognized to be a different point on the spectrum of dementia with Lewy bodies. In this book, we will refer to such cases of Parkinson’s disease dementia by the more inclusive term “dementia with Lewy bodies,” regardless of whether motor symptoms preceded cognitive symptoms. Older, infrequently used terms for dementia with Lewy bodies include diffuse Lewy body disease, dementia associated with cortical Lewy bodies, the Lewy body variant of Alzheimer’s disease, senile dementia of the Lewy body type, and Lewy body dementia.

Although it used to be regarded as uncommon, several autopsy studies have suggested that dementia with Lewy bodies accounts for up to 20% of cases of dementia ( ). Further, many clinical studies have found that dementia with Lewy bodies is the second most common cause of dementia in the older adult after Alzheimer’s disease, with one study finding a rate of dementia with Lewy bodies of 7.6% of all dementias ( ) and another found it was 22% of all patients with dementia over the age of 84 ( ). The incidence in a county in Minnesota was estimated at 5.9 per 100,000 ( ). Although some studies have suggested that the prognosis of patients with dementia with Lewy bodies is similar to those with Alzheimer’s disease, other studies suggest that patients with dementia with Lewy bodies show a more rapid decline in function, leading to earlier nursing home placement and death. Our clinical experience is that most patients with dementia with Lewy bodies do progress more rapidly than those with Alzheimer’s disease. The combination of Parkinsonism, dementia, and visual hallucinations typically leads to nursing home placement in 2–6 years, and death in 3–8 years. (There are, however, exceptions of patients who show a much slower disease progression.)

It is important to note that a subset of patients with dementia with Lewy bodies also meet clinical and pathological criteria for Alzheimer’s disease, with some studies suggesting an overlap of greater than 90% ( ). Not surprisingly, these patients’ dementias often present more like Alzheimer’s disease. Although some clinicians would label these patients as having the “Lewy body variant of Alzheimer’s disease,” we think a simpler and more accurate description is to simply state that these patients have a mixed dementia of Alzheimer’s disease and dementia with Lewy bodies.

Criteria and Diagnosis

The most important features of dementia with Lewy body are dementia (which must of course always be present), fluctuating cognition, visual hallucinations, and Parkinsonism ( Fig. 5-1 ). Additional features which are suggestive of the disorder include rapid eye movement (REM) sleep behavior disorder and neuroleptic sensitivity (that is, even small doses of neuroleptics may cause Parkinsonism). See Boxes 5-1 and 5-2 for a summary of the current clinical diagnostic criteria (see Chapter 3 for the DSM-5 general criteria for major and mild neurocognitive disorder). Regarding the Parkinsonism, it is important to note that up to 25% of patients with autopsy-proven dementia with Lewy bodies showed no signs of Parkinsonism during life, perhaps attributable to having mainly cortical and little brainstem pathology. See the section on the neurological examination below for more details on the Parkinsonism observed in this disorder.

Box 5-1

Selected Revised Criteria for Clinical Diagnosis of Dementia with Lewy Bodies

1.

Essential for a diagnosis:
- a.
  
  Dementia defined as progressive cognitive decline sufficient to interfere with normal social or occupational function. Impairment in attention, executive function, and visuospatial ability are often prominent. Memory impairment may or may not be prominent initially.
2.

Core features (two are sufficient for a diagnosis of probable dementia with Lewy bodies; one for a possible diagnosis):
- a.
  
  Fluctuating cognition (pronounced variations in attention and alertness).
- b.
  
  Visual hallucinations (recurrent, well-formed, detailed, of people and/or animals, often initially present around transitions between sleep and wake).
- c.
  
  Spontaneous features of Parkinsonism.
3.

Suggestive features (one or more plus one core feature allows a probable diagnosis; one or more without any core features allows a possible diagnosis):
- a.
  
  Rapid eye movement sleep behavior disorder.
- b.
  
  Severe neuroleptic sensitivity.
- c.
  
  Low dopamine transporter uptake in basal ganglia demonstrated by SPECT or PET imaging.
4.

Supportive features (commonly present but have not been proven to have diagnostic specificity):
- a.
  
  Repeated falls.
- b.
  
  Transient unexplained loss of consciousness.
- c.
  
  Orthostatic hypotension.
- d.
  
  Reduced occipital activity and generalized low uptake on SPECT/PET perfusion scan.
5.

A diagnosis of dementia with Lewy bodies is less likely:
- a.
  
  In the presence of clinically significant cerebrovascular disease noted on examination or radiology study.
- b.
  
  If Parkinsonism only appears for the first time at a stage of severe dementia.
- c.
  
  In the presence of any other disorder sufficient to account for some or all of the clinical picture.

Adapted from . Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium. Neurology 65, 1863–1872.

Box 5-2

DSM-5 Criteria for Major or Mild Neurocognitive Disorder with Lewy Bodies

A.

The criteria are met for major or mild neurocognitive disorder.
B.

The disturbance has insidious onset and gradual progression.
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 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.
- 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 behavior disorder.
  - b.
    
    Severe neuroleptic sensitivity.
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.