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

Hanneke F.M. Rhodius-Meester, Hilkka Liedes, Teddy Koene, Afina W. Lemstra, Charlotte Elisabeth Teunissen, Frederik Barkhof, Philip Scheltens, Mark van Gils, Jyrki Lötjönen, Wiesje M. van der Flier

    Research output: Contribution to journalArticleScientificpeer-review

    19 Citations (Scopus)


    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.
    Original languageEnglish
    Article number23
    JournalAlzheimer's Research and Therapy
    Issue number1
    Publication statusPublished - 20 Feb 2018
    MoE publication typeA1 Journal article-refereed


    The clinical database structure was developed with funding from Stichting Dioraphte. HFMRM is appointed on a grant from the European Union Seventh Framework Program project PredictND under grant agreement 611005.


    • Alzheimer's disease
    • diagnostic test assessment
    • mortality
    • prognosis


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