Survival and mortality differences between dementia with Lewy bodies vs Alzheimer disease

Abstract

Objective: To determine whether dementia with Lewy bodies (DLB) progresses more rapidly than Alzheimer disease (AD). Methods: We compared 315 participants (63 with DLB and 252 with AD) enrolled in a prospective longitudinal study of memory and aging with annual clinical and cognitive assessments and followed until death. The main outcome measure was dementia progression to institutionalization and death. Neuropathologic examinations were performed on all participants in this study. Subject classification (DLB vs AD) was based on neuropathology. Results: Patients with DLB had an increased risk of mortality vs patients with AD (hazard ratio [HR] 1.88, 95% CI: 1.4 to 2.5). The median survival time for DLB was 78.0 years and for AD was 84.6 years ( 2 ϭ 19.9, p Ͻ 0.001) with significant modification effects due to gender (HR 1.51, 95% CI: 1.0 to 2.3) and the presence of at least 1 APOE ε4 allele (HR 1.50, 95% CI: 1.0 to 2.2). Survival after dementia onset was also different between DLB and AD (7.3 vs 8.5 years; 2 ϭ 5.4, p Ͻ 0.02). DLB cases had similar risks of institutionalization and survival in long-term care facilities to AD cases. Self-reports of depression and the presence of extrapyramidal signs were important covariates. The rate of cognitive decline as measured by psychometric performance and clinical staging methods did not differ between DLB and AD. Conclusions: Dementia with Lewy bodies (DLB) increases the risk of mortality compared with Alzheimer disease (AD), but the two groups did not differ in rate of cognitive decline. The greater risk for noncognitive disease progression for DLB compared with AD suggests clinically meaningful differences for the two disorders. NEUROLOGY 2006;67:1935-1941 Dementia with Lewy bodies (DLB), a common cause of dementia after Alzheimer disease (AD), accounts for up to 30% of cases in autopsy series. 1-3 Consensus clinical criteria for diagnosis of DLB 4 are marked by poor sensitivity, particularly for those individuals with concurrent AD pathology. 5-7 Although a small percentage of DLB patients have only Lewy body (LB) pathology at autopsy, 6 the majority of patients with DLB have mixed AD and LB pathology. 4,6-9 This distinction has clinical relevance as patients with mixed pathology are often difficult to distinguish clinically from those with AD. 4,6,7 We therefore chose to examine outcomes in neuropathologically defined, rather than clinically defined, groups.Clinical progression of AD is well characterized, with mean duration of 8 to 12 years. 6,10 The clinical progression of DLB, however, has not fully been elucidated. There are conflicting reports in the literature regarding disease progression. Several earlier studies indicate that the time from diagnosis of DLB to death is 6 years or less, 11-13 with evidence of more rapid cognitive progression as compared with AD. 6,7,13 There are also reports demonstrating no difference in survival for DLB vs AD. 2, 14 We investigated whether DLB progresses more rapidly than AD to relevant clinical endpoints such as nursing home...

Synaptic proteins predict cognitive decline in Alzheimer's disease and Lewy body dementia

“…Less is known regarding the role of synaptic dysfunction in PDD and DLB [6,13,14], but synaptic alterations have been demonstrated in Parkinson`s disease [15] and preliminary studies have indicated early synaptic changes in DLB/PDD. Consistent with our hypothesis that synaptic dysfunction may be particularly important in DLB/PDD, structural imaging studies indicate that brain atrophy is less pronounced in DLB and PDD compared to AD [16] despite the more severe disease course [17,18]. Synaptic dysfunction has been also suggested to be caused by presynaptic accumulation of alpha-synuclein aggregates [19].…”

“…Post-mortem human brain tissue (from 129 cases in total) as well as brain sections (17)(18)(19) section/brain region) were provided by the Brains for Dementia Research network including cases from the Newcastle Brain Tissue Resource (21 cases), the Thomas Willis Oxford Brain Collections (17 cases) and the London Neurodegenerative Diseases Brain Bank (65 cases) as well as from the University Hospital Stavanger (26 cases). Autopsy protocols and sample collection was harmonized among all the centres.…”

Dying with Dementia: What We Know after More than a Decade of Research

“…Survival of dementia patients is highly variable between individuals and also across studies with median survival from diagnosis or study entry of generally being between 5 and 9 years [16][17][18][19]. Variation across studies may be explained by different ways of defining onset of the dementia, and different age of the population under study, and by statistical adjustments.…”

Resting bold fMRI differentiates dementia with Lewy bodies vs Alzheimer disease

“…There were no differences in age or education among the study participants; however, there were a higher proportion of men in the DLB group, consistent with previous reports. 32 The gender effect was taken into account when the group comparison of functional connectivity was conducted. Mini-Mental State Examination scores were lower in the AD and DLB groups compared with the cognitively normal group; however, the percentage of CDR 0.5 and CDR 1 cases did not differ between AD and DLB.…”