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

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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.
Original languageEnglish
Article number23
JournalAlzheimer's Research and Therapy
Volume10
Issue number1
DOIs
Publication statusPublished - 2018
MoE publication typeNot Eligible

Fingerprint

Dementia
Alzheimer Disease
Comorbidity
Mortality
Atrophy
Temporal Lobe
Cerebrospinal Fluid
Magnetic Resonance Imaging
Demography
Apolipoprotein E4
Neuropsychology
Apolipoproteins E
Threonine
Activities of Daily Living
Proportional Hazards Models
Amyloid
Genotype
Survival

Keywords

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

Cite this

Rhodius-Meester, H. F. M., Liedes, H., Koene, T., Lemstra, A. W., Teunissen, C. E., Barkhof, F., ... van der Flier, W. M. (2018). Disease-related determinants are associated with mortality in dementia due to Alzheimer's disease. Alzheimer's Research and Therapy, 10(1), [23]. https://doi.org/10.1186/s13195-018-0348-0
Rhodius-Meester, Hanneke F.M. ; Liedes, Hilkka ; Koene, Teddy ; Lemstra, Afina W. ; Teunissen, Charlotte Elisabeth ; Barkhof, Frederik ; Scheltens, Philip ; van Gils, Mark ; Lötjönen, Jyrki ; van der Flier, Wiesje M. / Disease-related determinants are associated with mortality in dementia due to Alzheimer's disease. In: Alzheimer's Research and Therapy. 2018 ; Vol. 10, No. 1.
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title = "Disease-related determinants are associated with mortality in dementia due to Alzheimer's disease",
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.",
keywords = "Alzheimer's disease, diagnostic test assessment, mortality, prognosis",
author = "Rhodius-Meester, {Hanneke F.M.} and Hilkka Liedes and Teddy Koene and Lemstra, {Afina W.} and Teunissen, {Charlotte Elisabeth} and Frederik Barkhof and Philip Scheltens and {van Gils}, Mark and Jyrki L{\"o}tj{\"o}nen and {van der Flier}, {Wiesje M.}",
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volume = "10",
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Rhodius-Meester, HFM, Liedes, H, Koene, T, Lemstra, AW, Teunissen, CE, Barkhof, F, Scheltens, P, van Gils, M, Lötjönen, J & van der Flier, WM 2018, 'Disease-related determinants are associated with mortality in dementia due to Alzheimer's disease', Alzheimer's Research and Therapy, vol. 10, no. 1, 23. https://doi.org/10.1186/s13195-018-0348-0

Disease-related determinants are associated with mortality in dementia due to Alzheimer's disease. / Rhodius-Meester, Hanneke F.M.; Liedes, Hilkka; Koene, Teddy ; Lemstra, Afina W.; Teunissen, Charlotte Elisabeth; Barkhof, Frederik; Scheltens, Philip; van Gils, Mark; Lötjönen, Jyrki; van der Flier, Wiesje M.

In: Alzheimer's Research and Therapy, Vol. 10, No. 1, 23, 2018.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Disease-related determinants are associated with mortality in dementia due to Alzheimer's disease

AU - Rhodius-Meester, Hanneke F.M.

AU - Liedes, Hilkka

AU - Koene, Teddy

AU - Lemstra, Afina W.

AU - Teunissen, Charlotte Elisabeth

AU - Barkhof, Frederik

AU - Scheltens, Philip

AU - van Gils, Mark

AU - Lötjönen, Jyrki

AU - van der Flier, Wiesje M.

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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.

KW - Alzheimer's disease

KW - diagnostic test assessment

KW - mortality

KW - prognosis

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U2 - 10.1186/s13195-018-0348-0

DO - 10.1186/s13195-018-0348-0

M3 - Article

VL - 10

JO - Alzheimer's Research and Therapy

JF - Alzheimer's Research and Therapy

SN - 1758-9193

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M1 - 23

ER -