Parkinson's Disease Dementia and Lewy Body Disease (original) (raw)

Dementia with Lewy Bodies (DLB) and Parkinson's disease dementia (PD-D) are Lewy body (LB)-related neurodegen-erative dementias sharing many clinical and neuropatholo-gical features. Both conditions affect cognition, behavior, movement, and autonomic functions. When the clinical picture is fully developed, DLB and PD-D are practically indistinguishable. Regarding molecular pathology, both are synucleinopathies, characterized by the accumulation of misfolded α-synuclein protein in the form of LBs and Lewy neurites. DLB and PD-D are believed to represent two entities on the same disease spectrum. The main difference between these two conditions is the temporal sequence of symptoms. Motor symptoms precede dementia in PD-D, whereas it coincides with or follows dementia in DLB within 1 year. Dementia with Lewy Bodies DLB is the second most common neurodegenerative dementia following Alzheimer's disease (AD). In contrast to AD, motor and behavioral symptoms appear early in the course of the disease in DLB and may be the major burden of the disease. Epidemiology and Risk Factors DLB accounts for 5% of all dementia cases over the age of 75. 1 In a systematic review, the prevalence of DLB was found to be between 0.02 and 33.3 per 1,000. 1 The incidence rate of DLB is 3.5 per 100,000 person-years overall, 2 and the incidence increases with age. 3 Risk factors associated with DLB are old age, mutations in the glucocerebrosidase (GBA) and α-synuclein genes, and carrying the H1 haplotype of the microtubule-associated protein tau (MAPT). 4-6 There are also new candidate risk genes associated with DLB such as BCL7C and GABRB3. 7 Compared with AD, the findings on apolipoprotein E4 (APOE) polymorphisms in DLB are inconclusive. Vascular risk factors are less associated with DLB compared with AD. Clinical Features The cardinal clinical features of DLB consist of motor, cog-nitive, behavioral, and autonomic symptoms. The cognitive profile is characterized by particularly severe deficits in attention as well as executive and visuospatial functions. In early phases of the disease, memory may be relatively Keywords ► dementia with Lewy bodies ► Parkinson's disease dementia ► synucleinopathy ► imaging Abstract Dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PD-D) are Lewy body-related neurodegenerative disorders sharing common clinical and neuropathological findings. The clinical features of both conditions include cognitive impairment, behavioral symptoms, autonomic dysfunction, sleep disorders, and parkinsonism. The cognitive profile of both disorders is characterized by particularly severe deficits in executive and visuospatial functions as well as attention. Clinical differentiation between DLB and PD-D is based on an arbitrary distinction between the time of onset of parkinsonism and cognitive symptoms; extrapyramidal symptoms precede dementia in PD-D, whereas it coincides with or follows dementia within 1 year in DLB. When the clinical picture is fully developed, DLB and PD-D are practically indistinguishable. Although the diagnosis is basically clinical, structural and functional neuroimaging as well as cerebrospinal fluid biomarkers may help the clinician in the diagnosis. Placebo-controlled randomized trials of the cholinesterase inhibitors have shown modest but significant benefits in cognition, global function, and neuropsychiatric symptoms in both disorders. Behavioral symptoms such as hallucinations and delusions should be treated with caution with antipsychotics, as they have the potential to worsen motor and cognitive symptoms.