Dataset Information

Long-Term Cognitive Decline in Dementia with Lewy Bodies in a Large Multicenter, International Cohort.

ABSTRACT: The aim of this study was to describe the rate and clinical predictors of cognitive decline in dementia with Lewy bodies (DLB), and compare the findings with Alzheimer's disease (AD) and Parkinson's disease dementia (PDD) patients.Longitudinal scores for the Mini-Mental State Examination (MMSE) in 1,290 patients (835 DLB, 198 PDD, and 257 AD) were available from 18 centers with up to three years longitudinal data. Linear mixed effects analyses with appropriate covariates were used to model MMSE decline over time. Several subgroup analyses were performed, defined by anti-dementia medication use, baseline MMSE score, and DLB core features.The mean annual decline in MMSE score was 2.1 points in DLB, compared to 1.6 in AD (p?=?0.07 compared to DLB) and 1.8 in PDD (p?=?0.19). Rates of decline were significantly higher in DLB compared to AD and PDD when baseline MMSE score was included as a covariate, and when only those DLB patients with an abnormal dopamine transporter SPECT scan were included. Decline was not predicted by sex, baseline MMSE score, or presence of specific DLB core features.The average annual decline in MMSE score in DLB is approximately two points. Although in the overall analyses there were no differences in the rate of decline between the three neurodegenerative disorders, there were indications of a more rapid decline in DLB than in AD and PDD. Further studies are needed to understand the predictors and mechanisms of cognitive decline in DLB.

SUBMITTER: Kramberger MG

PROVIDER: S-EPMC5392154 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Long-Term Cognitive Decline in Dementia with Lewy Bodies in a Large Multicenter, International Cohort.

Kramberger Milica G MG Auestad Bjørn B Garcia-Ptacek Sara S Abdelnour Carla C Olmo Josep Garre JG Walker Zuzana Z Lemstra Afina W AW Londos Elisabet E Blanc Frederic F Bonanni Laura L McKeith Ian I Winblad Bengt B de Jong Frank Jan FJ Nobili Flavio F Stefanova Elka E Petrova Maria M Falup-Pecurariu Cristian C Rektorova Irena I Bostantjopoulou Sevasti S Biundo Roberta R Weintraub Daniel D Aarsland Dag D

Journal of Alzheimer's disease : JAD 20170101 3

<h4>Background/objective</h4>The aim of this study was to describe the rate and clinical predictors of cognitive decline in dementia with Lewy bodies (DLB), and compare the findings with Alzheimer's disease (AD) and Parkinson's disease dementia (PDD) patients.<h4>Methods</h4>Longitudinal scores for the Mini-Mental State Examination (MMSE) in 1,290 patients (835 DLB, 198 PDD, and 257 AD) were available from 18 centers with up to three years longitudinal data. Linear mixed effects analyses with ap ...[more]

PMID: 28304294

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Project description:ImportancePlasma phosphorylated tau (p-tau) has proven to be an accurate biomarker for Alzheimer disease (AD) pathologic characteristics, offering a less expensive and less invasive alternative to cerebrospinal fluid (CSF) and positron emission tomography biomarkers for amyloid-β and tau. Alzheimer disease comorbid pathologic characteristics are common and are associated with more rapid cognitive decline in patients with dementia with Lewy bodies (DLB); therefore, it is anticipated that plasma p-tau concentrations may have utility in assessing cognitive impairment in individuals with this disorder.ObjectiveTo measure the concentrations of plasma p-tau (p-tau181 and p-tau231) and evaluate their associations with cognitive decline in individuals with probable DLB.Design, setting, and participantsThis multicenter longitudinal cohort study included participants from the European-DLB (E-DLB) Consortium cohort enrolled at 10 centers with harmonized diagnostic procedures from January 1, 2002, to December 31, 2020, with up to 5 years of follow-up. A total of 1122 participants with plasma samples were available. Participants with acute delirium or terminal illness and patients with other previous major psychiatric or neurologic disorders were excluded, leaving a cohort of 987 clinically diagnosed participants with probable DLB (n = 371), Parkinson disease (n = 204), AD (n = 207), as well as healthy controls (HCs) (n = 205).Main outcomes and measuresThe main outcome was plasma p-tau181 and p-tau231 levels measured with in-house single molecule array assays. The Mini-Mental State Examination (MMSE) was used to measure cognition.ResultsAmong this cohort of 987 patients (512 men [51.9%]; mean [SD] age, 70.0 [8.8] years), patients with DLB did not differ significantly regarding age, sex, or years of education from those in the AD group, but the DLB group was older than the HC group and included more men than the AD and HC groups. Baseline concentrations of plasma p-tau181 and p-tau231 in patients with DLB were significantly higher than those in the HC group but lower than in the AD group and similar to the Parkinson disease group. Higher plasma concentrations of both p-tau markers were found in a subgroup of patients with DLB with abnormal CSF amyloid-β42 levels compared with those with normal levels (difference in the groups in p-tau181, -3.61 pg/mL; 95% CI, -5.43 to -1.79 pg/mL; P = .049; difference in the groups in p-tau231, -2.51 pg/mL; 95% CI, -3.63 to -1.39 pg/mL; P = .02). There was no difference between p-tau181 level and p-tau231 level across confirmed AD pathologic characteristcs based on reduced Aβ42 level in CSF in individuals with DLB. In DLB, a significant association was found between higher plasma p-tau181 and p-tau231 levels and lower MMSE scores at baseline (for p-tau181, -0.092 MMSE points; 95% CI, -0.12 to -0.06 MMSE points; P = .001; for p-tau231, -0.16 MMSE points; 95% CI, -0.21 to -0.12 MMSE points; P < .001), as well as more rapid MMSE decline over time. Plasma p-tau181 level was associated with a decrease of -0.094 MMSE points per year (95% CI, -0.144 to -0.052 MMSE points; P = .02), whereas plasma p-tau231 level was associated with an annual decrease of -0.130 MMSE points (95% CI, -0.201 to -0.071 MMSE points; P = .02), after adjusting for sex and age.Conclusions and relevanceThis study suggests that plasma p-tau181 and p-tau231 levels may be used as cost-effective and accessible biomarkers to assess cognitive decline in individuals with DLB.

Dataset Information

Long-Term Cognitive Decline in Dementia with Lewy Bodies in a Large Multicenter, International Cohort.

Publications

Long-Term Cognitive Decline in Dementia with Lewy Bodies in a Large Multicenter, International Cohort.

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