Lewy body disorders
The members of the Dementia With Lewy Bodies/Parkinson’s Disease With Dementia working group have endorsed the term “Lewy body disorders” as the umbrella term for Parkinson disease, Parkinson disease with dementia, and dementia with Lewy bodies.30 All of these disorders share a mechanism of neurodegeneration involving a-synuclein metabolism.
A “Lewy body” is an intracytoplasmic neuronal inclusion that contains a-synuclein; a “Lewy neurite” is an inclusion confined to neuronal processes (axons and dendrites) that contains a-synuclein. An important clinical consideration is that many patients with Lewy body disorders have coexisting pathologies, such as Alzheimer and vascular dementia.
Dementia with Lewy bodies. Neuropathological data suggest that approximately 15% to 30% of all dementias are associated with Lewy bodies.31 Dementia with Lewy bodies is thought to be the second most common subtype of dementia. Epidemiological clinical studies show the prevalence of dementia with Lewy bodies to be as high as 5% in the general population and that it is the cause of up to 30.5% of all dementia cases.31
The Dementia With Lewy Bodies Consortium revised dementia with Lewy bodies criteria in its third report. The central feature is dementia, and core features are fluctuating cognition with pronounced variations in attention and alertness, recurrent visual hallucinations that are typically well formed and detailed, and spontaneous features of parkinsonism.32 Neuropathology demonstrates a wide spectrum of Lewy bodies with a broad distribution from brain stem to cortex and concurrent AD pathology in many cases. Cholinergic loss is greater in dementia with Lewy bodies than in AD.
Nonpharmacological interventions for patients with other types of dementia can also be helpful—such as improving sensory impairments, environmental structuring, and caregiver education.
Pharmacological treatment with cholinesterase inhibitors is the current strategy for cognitive impairment associated with dementia with Lewy bodies. The evidence for memantine(Drug information on memantine) is mixed.33 Patients with dementia with Lewy bodies are sensitive to antipsychotics; if antipsychotics are necessary, consider prescribing those agents least likely to cause extrapyramidal adverse effects. Tricyclic antidepressants, low-potency neuroleptics, antiparkinsonian anticholinergic drugs, and antispasmodics for the bladder or GI tract should be avoided if possible, because of orthostatic hypotension and worsening of cognition and psychotic symptoms.34
Parkinson disease and Parkinson disease with dementia. Dementia has been reported in about 20% to 44% of patients with Parkinson disease, although the range is 10% to 90%.35 Risk factors for dementia include early executive impairment, lower baseline mini-mental state examination scores, older age, possibly older age at onset of Parkinson disease, more severe disease, hallucinations, depression, and dementia in other family members.
The cognitive impairment in classic Parkinson disease is called dysexecutive syndrome, which includes psychomotor slowing and executive, attention, and visuospatial impairments. Memory impairment involves poor retrieval, and dementia is usually seen several years after the onset of motor symptoms. The Movement Disorder Study Task Force has proposed clinical diagnostic criteria for Parkinson disease dementia.36
Histopathological hallmarks are Lewy bodies and Lewy neurites. Lewy pathology begins at the brain stem, ascends to the substantia nigra, and finally ascends to the cerebral cortex, where Lewy pathology is associated with significant cognitive impairment. Dopaminergic, serotonergic, noradrenergic, and cholinergic deficits are associated with cognitive impairment.
Nonpharmacological interventions include educating caregivers about disease progression and about community resources. Cholinesterase inhibitors (donepezil, rivastigmine(Drug information on rivastigmine), galantamine(Drug information on galantamine), tacrine(Drug information on tacrine)) may be beneficial in Parkinson disease with dementia.36,37 Rivastigmine is FDA-approved for Parkinson disease with dementia.38 The Quality Standards Subcommittee of the American Academy of Neurology has determined that improvement with cholinesterase inhibitors is modest and that adverse motor effects may occur.39