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Disease-related determinants are associated with mortality in dementia due to Alzheimer's disease

Rhodius-Meester, HFM; Liedes, H; Koene, T; Lemstra, AW; Teunissen, CE; Barkhof, F; Scheltens, P; ... van der Flier, WM; + view all (2018) Disease-related determinants are associated with mortality in dementia due to Alzheimer's disease. Alzheimer's Research & Therapy , 10 (1) , Article 23. 10.1186/s13195-018-0348-0. Green open access

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Abstract

BACKGROUND: Survival after dementia diagnosis varies considerably. Previous studies were focused mainly on factors related to demographics and comorbidity rather than on Alzheimer's disease (AD)-related determinants. We set out to answer the question whether markers with proven diagnostic value also have prognostic value. We aimed to identify disease-related determinants associated with mortality in patients with AD. METHODS: We included 616 patients (50% female; age 67 ± 8 years; mean Mini Mental State Examination score 22 ± 3) with dementia due to AD from the Amsterdam Dementia Cohort. Information on mortality was obtained from the Dutch Municipal Register. We used age- and sex-adjusted Cox proportional hazards analysis to study associations of baseline demographics, comorbidity, neuropsychology, magnetic resonance imaging (MRI) (medial temporal lobe, global cortical and parietal atrophy, and measures of small vessel disease), and cerebrospinal fluid (CSF) (β-amyloid 1-42, total tau, and tau phosphorylated at threonine 181 [p-tau]) with mortality (outcome). In addition, we built a multivariate model using forward selection. RESULTS: After an average of 4.9 ± 2.0 years, 213 (35%) patients had died. Age- and sex-adjusted Cox models showed that older age (HR 1.29 [95% CI 1.12-1.48]), male sex (HR 1.60 [95% CI 1.22-2.11]), worse scores on cognitive functioning (HR 1.14 [95% CI 1.01-1.30] to 1.31 [95% CI 1.13-1.52]), and more global and hippocampal atrophy on MRI (HR 1.18 [95% CI 1.01-1.37] and HR 1.18 [95% CI 1.02-1.37]) were associated with increased risk of mortality. There were no associations with comorbidity, level of activities of daily living, apolipoprotein E (APOE) ε4 status, or duration of disease. Using forward selection, the multivariate model included a panel of age, sex, cognitive tests, atrophy of the medial temporal lobe, and CSF p-tau. CONCLUSIONS: In this relatively young sample of patients with AD, disease-related determinants were associated with an increased risk of mortality, whereas neither comorbidity nor APOE genotype had any prognostic value.

Type: Article
Title: Disease-related determinants are associated with mortality in dementia due to Alzheimer's disease
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1186/s13195-018-0348-0
Publisher version: https://doi.org/10.1186/s13195-018-0348-0
Language: English
Additional information: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Keywords: Alzheimer’s disease, Diagnostic test assessment, Mortality, Prognosis
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Brain Repair and Rehabilitation
URI: https://discovery.ucl.ac.uk/id/eprint/10044813
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