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

Alzheimer’s Research & Therapy

Afina W. Lemstra¹  Hanneke F. M. Rhodius-Meester¹  Philip Scheltens¹  Wiesje M. van der Flier¹  Ted Koene²  Frederik Barkhof³  Charlotte E. Teunissen⁴  Jyrki Lötjönen⁵  Mark van Gils⁵  Hilkka Liedes⁵ 

[1] Alzheimer Center, Department of Neurology, VU University Medical Center, Amsterdam Neuroscience;Department of Medical Psychology, VU University Medical Center, Amsterdam Neuroscience;Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam Neuroscience;Neurochemistry Lab and Biobank, Department of Clinical Chemistry, VU University Medical Center, Amsterdam Neuroscience;VTT Technical Research Center of Finland Ltd;

关键词: Alzheimer’s disease;    Prognosis;    Mortality;    Diagnostic test assessment;   

DOI  :  10.1186/s13195-018-0348-0

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown