Lewy Body dementia (LBD)

Introduction

a type of dementia closely allied to both Alzheimer's dementia (AD) and Parkinson's disease
often has a rapid or acute onset, with especially rapid decline in the first few months
there is a spectrum of disease associated with presence of Lewy bodies and Lewy neurites (these were 1st discovered by Lewy in 1911) which includes:
- Lewy Body dementia (LBD) aka Dementia with Lewy bodies (DLB) - Lewy bodies primarily in the cortical regions
- Parkinson's disease dementia (PDD) - Lewy bodies primarily in the subcortical basal ganglia
- Parkinson's disease

5% and 25% of diagnosed dementias in older adults are due to one of the Lewy body dementias
usually develops after the age of 50 and typically occurs in those aged 65 or older
men > women
eg. the actor Robin Williams

most cases are sporadic
genetic predispositions:¹⁾
- key genetic associations reflect genetic overlap with both Parkinson's and Alzheimer's diseases and include:
  - the SNCA gene (alpha-synuclein aggregation)
    - the core protein that misfolds and clumps into Lewy bodies
  - GBA variants (increasing risk two to threefold)
    - encodes the lysosomal enzyme beta-glucocerebrosidase;
    - heterozygous mutations heavily increase the risk for both Parkinson's disease and LBD.
  - the Alzheimer-linked APOE ε4 allele
    - elevates disease susceptibility and alters cognitive progression, showing a genetic bridge to Alzheimer's disease pathology
  - SNCB
    - encodes beta-synuclein
    - rare variants occasionally implicated in familial early-onset synucleinopathies

characterized anatomically by the presence of Lewy bodies, clumps of alpha-synuclein and ubiquitin protein in neurons
the two dementias (LBD and PDD) show remarkably convergent neuropathological changes at autopsy

often has a rapid or acute onset, with especially rapid decline in the first few months.
fluctuating cognition with great variations in attention and alertness from day to day and hour to hour
recurrent visual hallucinations in 75% pts
motor features of Parkinson's
often have frequent falls &/or postural hypotension/syncope
rapid eye movement sleep behavior disorder
one of the most clinically critical and distinctive features is hypersensitivity to neuroleptic and antiemetic medications that affect dopaminergic and cholinergic systems as they may become catatonic, lose cognitive function and/or develop life-threatening muscle rigidity (neuroleptic malignant syndrome (NMS))

often misdiagnosed
cognitive assessment
MRI
the ‘one year rule’ is used to assess the temporal onset of dementia versus parkinsonism, in order to differentiate the two diseases.
- if parkinsonism occurs at the same time or within 1 year of dementia, a diagnosis of LBD is made,
- whereas if parkinsonism precedes the onset of dementia by a year or more, PDD is diagnosed.

¹⁾