Chapter 11 Lewy Body Dementia

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Dementia is becoming increasingly prevalent since elderly patients are living longer due to the development of treatments for other diseases and conditions. The percent of our population over 60 is also increasing with the wave of aging baby boomers. Additionally, more individuals seek medical assistance for cognitive problems as visibility for treatments improves. This combination of factors results in the dementia syndromes becoming more common, causing physicians to encounter more patients with dementia as well as more caregivers of these patients.

Of dementia subtypes, Alzheimer's disease (AD) is the most common. Dementia with Lewy bodies (DLB) is thought to be the second most common subtype. DLB's typical symptoms include cognitive impairment, visual hallucinations, spontaneous parkinsonism, and fluctuating confusion. Supportive features include a variety of sleep disruptions that may occur before manifestations of dementia. Psychiatric symptoms include vivid visual hallucinations and depression. The clinical features of DLB are strikingly similar to those of dementia in Parkinson's disease (PD).

The underlying biology of DLB is complex, but the presence of alpha‐synuclein containing Lewy bodies (LB) is a common factor. These inclusions also contain ubiquitin. PD dementia shares these pathological findings with DLB, as well as neural degeneration of the substantia nigra. DLB and dementia in PD may represent the same pathological process along a disease spectrum. Additionally, many DLB cases are also associated with beta‐amyloid and tau‐containing neurofibrillary tangles, features that are associated with AD. Frequently, AD patients are also found to have LB. The reason for this overlap is unknown. However, the greater the Alzheimer's pathology in DLB patients, the more the clinical features of DLB overlaps with AD.

In this chapter, we will review DLB including clinical, pathological, and radiological features as well as biomarkers and treatments.

Introduction

Dementia is defined as a syndrome of progressive cognitive impairment that interferes with daily function (DSM IV‐TR, 2004). The cognitive areas involved include memory, language, abstract thinking, visuo‐spatial skills, behavior, and personality. Alzheimer's disease (AD) is the most common dementia subtype, representing over half of all dementias. Dementia with Lewy bodies (DLB) is the second most common type of dementia at 20%, affecting 15–25% of elderly demented patients (McKeith et al., 1996). Of those patients with Parkinson's disease (PD), 30% will develop dementia during the course of their illness (Emre et al., 2007). Many more Parkinson's patients will experience some type of cognitive change. Table I compares the most common forms of dementia.

The four main components of the DLB syndrome are dementia, visual hallucinations, parkinsonism, and fluctuation of symptoms, particularly confusion. The cognitive decline associated with DLB includes pronounced variation in attention and alertness. Visual hallucinations are recurrent, consist of formed or detached figures and typically occur early in the disease course. The parkinsonian motor features include myoclonus, bradykinesia, rigidity, and less commonly tremors. Additional associated features include sleep anomalies, repeated falls, syncope, transient loss of consciousness, delusions that are often paranoid, urinary incontinence, and depression. DLB patients are sometimes oversensitive to neuroleptic agents, and use of such medication may precipitate a change in functional status.

DLB exhibits a clinical overlap with both the dementia of AD and the motor symptoms of PD. DLB is characterized by intracytoplamic proteinaceous inclusions called Lewy bodies (LB). These collections of alpha‐synuclein (AS) plaques occur throughout the cortex and subcortical regions. Additionally, DLB has a loss of acetylcholine producing neurons similar to those seen in AD and a loss of dopaminergic neurons, as seen in PD.

This chapter will review DLB clinical and pathologic features, radiographic findings, biomarkers, and current treatment modalities.

Section snippets

DLB Clinical Features

In 2005, the DLB consortium issued its third report on the Current International Consensus Diagnostic Criteria for DLB (McKeith et al., 2005). The central features necessary for a diagnosis of DLB include the presence of a dementia, fluctuating cognition, hallucinations, and parkinsonian symptoms. Numerous supportive features are commonly found in DLB patients, but are not necessary for the diagnosis.

As in AD, DLB patients have a progressive cognitive decline sufficient enough to interfere with

PD‐D

PD‐D is a dementia syndrome that develops in the context of an established PD. PD‐D has an insidious onset with slow progression, and is defined as having impairment in more than one cognitive domain representing a decline from premorbid level. The deficits present must be severe enough to impair daily life and the deficits must be independent of the impairment by motor or autonomic symptoms (Emre et al., 2007). Such impairments may affect social functioning, occupational productivity, or

DLB and PD‐D

There is no clinical rational or pathological basis that determines a definite time interval between development of motor symptoms and onset of dementia in differentiating PD‐D from DLB. In general, a diagnosis of PD‐D should be made when dementia develops within the context of established PD, while DLB should be diagnosed when dementia occurs before or concurrently within 1 year of parkinsonism (McKeith et al., 2005).

Often patients do not fit into either pattern above. Many times early

Pathology

Found in 50% of dementia patients (Hamilton, 2000, Lippa et al., 1998), the main identifying pathologic feature of DLB is the LB. LB are spherical intracytoplasmic protein deposits around the nucleus and throughout the dendrite of subcortical and cortical neurons. They consist of filamentous protein granules composed of AS and ubiquitin, and are surrounded by a halo of neurofilaments. Widespread LB differentiate the LB dementias from other dementia subtypes. The number of LB present does not

Genetics

In most cases, the LB diseases occur sporadically. Fully penetrate genetic causes for DLB are rare; however, there are likely additional genetic and environmental susceptibility factors that are still unidentified. There are a variety of genetic etiologies for dementia, with most being caused by abnormal CNS protein processing, expression, or aggregation. Many different types of cellular damage cause aggregation of a variety of CNS proteins, and no single cause has been linked to dementias.

Biomarkers

There are currently no highly sensitive clinical diagnostic criteria that distinguish DLB from other dementia subtypes with certainty, but this could be aided by biomarkers for DLB. Aarsland recently reviewed antemortem markers that aid in the diagnosis (Aarsland et al., 2008). This study determined that, “The best evidence was for scintigraphy of the striatal dopamine transporter system using FP‐CIT SPECT. Several small scintigraphy studies of cardiovascular autonomic function using

Management

The treatment and management of DLB patients is complicated by their neuropsychiatric profile and extrapyramidal signs. Cognitive impairment must be addressed in the context of hallucinations, apathy, depression, and sleep disorders. Functional status is compounded by the increased morbidity of physical symptoms. Postural instability, continence, bradykinesia, syncope, falls, and autonomic instability worsen DLB functional impairment. All these factors must be considered when deriving a

References (44)

  • (2004)
  • M. Baba et al.

    Aggregation of alpha‐synuclein in Lewy bodies of sporadic Parkinson's disease and dementia with Lewy bodies

    Am. J. Pathol.

    (1998)
  • C.G. Ballard et al.

    Cholinesterase inhibitors reduce cortical Abeta in dementia with Lewy bodies

    Neurology

    (2007)
  • R. Barber et al.

    Dementia with Lewy bodies: Diagnosis and management

    Int. J. Geriatr. Psychiatr.

    (2001)
  • B.F. Boeve et al.

    REM sleep behavior disorder in Parkinson's disease and dementia with Lewy bodies

    J. Geriatr. Psychiatr. Neurol.

    (2004)
  • B.F. Boeve et al.

    Pathophysiology of REM sleep behavior disorder and relevance to neurodegenerative disease

    Brain

    (2007)
  • D.J. Burn et al.

    Current treatment of dementia with Lewy bodies and dementia associated with Parkinson's disease

    Mov. Disord.

    (2003)
  • D.J. Burn et al.

    Extrapyramidal features in Parkinson's disease with and without dementia and dementia with Lewy bodies: A cross‐sectional comparative study

    Mov. Disord.

    (2003)
  • D.J. Connor et al.

    Cognitive profiles of autopsy‐confirmed Lewy body variant vs pure Alzheimer disease

    Arch. Neurol.

    (1998)
  • J.E. Duda et al.

    Novel antibodies to synuclein show abundant striatal pathology in Lewy body diseases

    Ann. Neurol.

    (2002)
  • M. Emre et al.

    Clinical diagnostic criteria for dementia associated with Parkinson's disease

    Mov. Disord.

    (2007)
  • S. Fahn et al.

    Unified Parkinson's disease rating scale

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