Dementia with Lewy bodies

Etiology
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By Ann Marie Hake MD

The presence and density of cortical Lewy bodies correlates best with the degree of dementia in patients with dementia with Lewy bodies and is thought to be a marker for the underlying pathogenesis (see the Pathogenesis and pathophysiology section below) (Irwin et al 2012). The disorders in the spectrum of diseases with Lewy bodies that clinically includes dementia with Lewy bodies, Parkinson disease, and Parkinson disease with dementia are likely to share similar origins. Although dementia with Lewy bodies (defined principally in terms of its cognitive symptoms) and Parkinson disease (first recognized mainly as a motor disorder) are currently classified as two different conditions, advances in knowledge of the spectrum of Lewy body disorders has led the International Parkinson and Movement Disorders Society to establish a task force to evaluate whether a change in the definition of these diseases is warranted (Berg et al 2014).

As in other neurodegenerative diseases, it is suspected that environmental, genetic, and aging factors contribute to the risk of developing dementia with Lewy bodies (Tsuang et al 2004). The existence of “pure” dementia with Lewy bodies seems to be the exception rather than the rule; published autopsy series report concomitant pathology in more than 90% of individuals who had dementia. Concomitant Alzheimer disease pathology is the most common, with one-half to two-thirds of cases meeting diagnostic criteria for Alzheimer disease in addition to dementia with Lewy bodies; other pathology that can coexist includes cerebrovascular pathology and hippocampal sclerosis (Barker et al 2002; Schneider et al 2007; Nelson et al 2010; Graff-Radford et al 2014).

Although multiple cases within same families have been reported, there does not seem to be a strong tendency for inheriting the disease (Brett et al 2002; Galvin et al 2002; Harding et al 2004). Genetic studies are making some progress in revealing a matrix of different genes that may contribute to development of dementia with Lewy bodies and Lewy body disorders. The influence of genetic factors appears to be complex, but may explain the relationship between dementia with Lewy bodies and the other primary Lewy body disorders, including Parkinson disease, and its association with Alzheimer disease, especially the autosomal dominant forms of Alzheimer disease (Tsuang et al 2004; Leverenz et al 2006). Genes that have been associated with Lewy bodies and dementia with Lewy bodies include the following:

  • Alpha-synuclein (SNCA; 163890)
  • Beta-synuclein (SNCB; 602569)
  • Familial Parkinson disease-1 (PARK1; 168601)
  • Leucine-rich repeat kinase 2 (LRRK2; 609007)
  • Parkinson disease-8 (PARK8; 607060)
  • Synphyllin-1 (SNCAIP; 603779)
  • Apolipoprotein E (APOE; 107741)
  • Presenilin-1 (PSEN1; 104311)
  • Presenilin-2 (PSEN2; 600759) (Raciti et al 2011)
  • Amyloid precursor protein (APP; 104760) (Guyant-Marechal et al 2008)
  • Debrisoquine 4-hydroxylase (cytochrome P450 2D6) (CYP2D6; 124030)
  • Prion protein (PRNP; 176640)
  • Glucocerebrosidase (GBA; 606463)
  •  Niemann-Pick disease, type C1 (NPC1; 606463)

In This Article

Introduction
Historical note and nomenclature
Clinical manifestations
Clinical vignette
Etiology
Pathogenesis and pathophysiology
Epidemiology
Prevention
Differential diagnosis
Diagnostic workup
Prognosis and complications
Management
Anesthesia
References cited
Contributors