Dementia with Lewy bodies and Parkinson's disease

doi:10.1016/j.parkreldis.2003.12.005

Parkinsonism & Related Disorders

Volume 10, Supplement 1, May 2004, Pages S15-S18

https://doi.org/10.1016/j.parkreldis.2003.12.005 Get rights and content

Abstract

Lewy bodies (LB) in the central nervous system are associated with several different clinical syndromes including Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Long term follow up of PD patients finds up to 78% eventually develop dementia, most of these patients exhibiting fluctuating cognition and visual hallucinations similar to DLB and with extensive cortical LB at autopsy. α-Synuclein positive, neuritic pathology, in the putamen of DLB and Parkinson's disease dementia (PDD), may contribute to postural-instability gait difficulty, parkinsonism, diminished levodopa responsiveness and increased neuroleptic sensitivity. Cognitive and neuropsychiatric symptoms improve with cholinesterase inhibitor treatment in both patient groups. DLB and PDD should be seen as different points on a spectrum of LB disease. Distinguishing them as separate disorders may be useful in clinical practice, but may be of limited value in terms of investigating and treating the underlying neurobiology.

Section snippets

Lewy body disease as a spectrum disorder

Dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) are two common syndromes with overlapping clinical symptoms suggesting that they probably represent different points on a spectrum of Lewy body (LB) disease sharing similar underlying neuropathological processes. In contrast with earlier cross-sectional estimates of 25–30% dementia prevalence in PD [1], longitudinal studies find 78% meet DSM IIIR criteria for dementia [2] after an average of a decade of motor symptoms [3] (

Clinical diagnosis

Consensus guidelines for DLB [9] suggest that PD patients, who develop dementia more than 12 months after the initial motor symptoms should be diagnosed as PDD rather than DLB. The central feature required for a diagnosis of DLB is progressive cognitive decline, severe enough to cause social and occupational functional impairment. Core features are fluctuating cognition, recurrent and persistent visual hallucinations, and extrapyramidal motor symptoms (EPS). Guidelines recommend that two of the

Neuropathology

Brainstem and cortical LB are the only features considered essential for a pathologic diagnosis of DLB, although Lewy neurites (LN), concomitant cortical senile plaques, sparse tau-pathology, and spongiform changes may also be seen [13], [14]. Coincident AD or vascular pathology fulfilling neuropathological diagnosis of AD or vascular dementia also occurs in DLB and PDD and may modify the clinical presentation. LB and LN contain α-synuclein suggesting neurobiological links with other

Neuropsychology

Prominent executive, attentional and visuospatial dysfunctions with relatively preserved memory functions are characteristic neuropsychological findings in DLB and PDD [9]. Fluctuation of cognition and attention interfere with cognitive assessments and lead to high variability of cognitive performance [18]. Fluctuating cognition measured using computerised tests of attentional speed show no differences between DLB and PDD patients [19].

Differential diagnosis and investigation

Major syndromes to be considered for differential diagnosis are other degenerative brain disorders with EPS, neuropsychiatric syndromes with visual hallucinations, and syndromes with profound fluctuation in cognition. The diagnoses most likely to be confused with DLB are Alzheimer's disease, vascular cognitive impairment, delirium of unexplained aetiology or Creutzfeldt–Jacob disease. The standard EEG in DLB may show early slowing, epoch by epoch fluctuation and transient temporal slow wave

Clinical management

It is the combination of EPS and neuropsychiatric features which makes pharmacological treatment of DLB and PDD patients very difficult, and often leads to situations where the improvement of one symptom may only be achieved at the expense of another. The neurochemical dysfunction in DLB and PDD suggest combined cholinergic and dopaminergic deficits implying need to avoid medications with anticholinergic effects or side effects of dopaminergic antagonism. Tricyclic antidepressants, low potency

Conclusions

DLB and PDD share similar clinical and neuropathological features. The aetiology of both disorders and mechanisms triggering the spread of subcortical pathology in PD are unknown. Ongoing and future research has to clarify whether PDD and DLB are different representations of the same neurobiological process with different initial manifestation, or whether they are independent diseases ending in a similar common pathway. Accumulating evidence favours the former option. Current clinical Consensus

Acknowledgements

UPM was supported by the Swiss Association for Parkinson's disease.

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ReviewDementia with Lewy bodies and Parkinson's disease

Abstract

Section snippets

Lewy body disease as a spectrum disorder

Clinical diagnosis

Neuropathology

Neuropsychology

Differential diagnosis and investigation

Clinical management

Conclusions

Acknowledgements

Lancet

Lancet Neurol

Lancet

Prevalence, and characteristics of dementia in Parkinson disease: an 8-year prospective study

Arch Neurol

A 10-year study of the incidence of and factors predicting dementia in Parkinson's disease

Neurology

Which factors predict cognitive decline in Parkinson's disease?

J Neurol Neurosurg Psychiatry

Antecedent clinical features associated with dementia in Parkinson's disease

Neurology

Prodromal frontal/executive dysfunction predicts incident dementia in Parkinson's disease

J Int Neuropsychol Soc

Mental symptoms in Parkinson's disease are important contributors to caregiver distress

Int J Geriatr Psychiatry

Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB international workshop

Neurology

Report of the second dementia with Lewy body international workshop: diagnosis and treatment. Consortium on dementia with Lewy bodies

Neurology

Comparison of extrapyramidal signs in dementia with Lewy bodies and Parkinson's disease

J Neuropsychiatry Clin Neurosci

Parkinson disease neuropathology: later-developing dementia and loss of the levodopa response

Arch Neurol

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J Neurol Transm Suppl

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Review
Dementia with Lewy bodies and Parkinson's disease