Generic placeholder image

Current Alzheimer Research


ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

Research Article

Cerebrospinal Fluid Biomarker Levels as Markers for Nursing Home Placement and Survival Time in Alzheimer’s Disease

Author(s): Carina Wattmo*, Kaj Blennow and Oskar Hansson

Volume 18, Issue 7, 2021

Published on: 22 October, 2021

Page: [573 - 584] Pages: 12

DOI: 10.2174/1567205018666211022164952

open access plus


Background: Cerebrospinal Fluid (CSF) biomarkers are associated with conversion from mild cognitive impairment to Alzheimer’s Disease (AD), but their predictive value for later end-points has been less evaluated with inconsistent results.

Objective: We investigated potential relationships between CSF amyloid-β1-42 (Aβ42), Phosphorylated tau (P-tau), and Total tau (T-tau) with time to Nursing Home Placement (NHP) and life expectancy after diagnosis.

Methods: This prospective observational study included 129 outpatients clinically diagnosed with mild-to-moderate AD who underwent a lumbar puncture. The CSF biomarkers were analysed with xMAP technology. Dates of institutionalisation and death were recorded.

Results: After 20 years of follow-up, 123 patients (95%) were deceased. The participants with abnormal P-tau and T-tau (A+ T+ (N)+) died earlier than those with normal P-tau/abnormal T-tau (A+ T- (N)+) (mean, 80.5 vs. 85.4 years). Linear associations were demonstrated between lower Aβ42 and shorter time to NHP (p = 0.017), and higher P-tau and younger age at death (p = 0.016). No correlations were detected between survival after AD diagnosis and CSF biomarkers. In sexand- age-adjusted Cox regression models, higher P-tau and T-tau were independent predictors of shorter lifespan after diagnosis. In multivariate Cox models, older age and lower baseline cognitive status, but not elevated tau, significantly precipitated both institutionalisation and death.

Conclusion: These findings suggest that CSF biomarker levels plateau in the dementia phase of AD, which may limit their possible relationships with clinical end-points, such as NHP and survival time. However, the biomarkers reflect the central pathophysiologies of AD. In particular, pathologic tau is associated with more advanced disease, younger age at onset, and earlier death.

Keywords: Alzheimer's disease, nursing home placement, mortality, longitudinal study, predictors, CSF biomarkers, AT(N), Tau.

Prince M, Prina M, Guerchet M. World Alzheimer Report 2013 Journey of Caring An analysis of long-term care for dementia. London: Alzheimer’s Disease International 2013.
Hatoum HT, Thomas SK, Lin SJ, Lane R, Bullock R. Predicting time to nursing home placement based on activities of daily living scores--a modelling analysis using data on Alzheimer’s disease patients receiving rivastigmine or donepezil. J Med Econ 2009; 12(2): 98-103.
[] [PMID: 19492974]
Cepoiu-Martin M, Tam-Tham H, Patten S, Maxwell CJ, Hogan DB. Predictors of long-term care placement in persons with dementia: a systematic review and meta-analysis. Int J Geriatr Psychiatry 2016; 31(11): 1151-71.
[] [PMID: 27045271]
Gaugler JE, Kane RL, Kane RA, Clay T, Newcomer R. Caregiving and institutionalization of cognitively impaired older people: utilizing dynamic predictors of change. Gerontologist 2003; 43(2): 219-29.
[] [PMID: 12677079]
Wattmo C, Wallin AK, Londos E, Minthon L. Risk factors for nursing home placement in Alzheimer’s disease: a longitudinal study of cognition, ADL, service utilization, and cholinesterase inhibitor treatment. Gerontologist 2011; 51(1): 17-27.
[] [PMID: 20562471]
Larson EB, Shadlen MF, Wang L, et al. Survival after initial diagnosis of Alzheimer disease. Ann Intern Med 2004; 140(7): 501-9.
[] [PMID: 15068977]
Rountree SD, Chan W, Pavlik VN, Darby EJ, Doody RS. Factors that influence survival in a probable Alzheimer disease cohort. Alzheimers Res Ther 2012; 4(3): 16.
[] [PMID: 22594761]
Wattmo C, Londos E, Minthon L. Longitudinal associations between survival in Alzheimer’s disease and cholinesterase inhibitor use, progression, and community-based services. Dement Geriatr Cogn Disord 2015; 40(5-6): 297-310.
[] [PMID: 26335053]
Tilvis RS, Strandberg TE, Juva K. Apolipoprotein E phenotypes, dementia and mortality in a prospective population sample. J Am Geriatr Soc 1998; 46(6): 712-5.
[] [PMID: 9625186]
Buchhave P, Minthon L, Zetterberg H, Wallin AK, Blennow K, Hansson O. Cerebrospinal fluid levels of β-amyloid 1-42, but not of tau, are fully changed already 5 to 10 years before the onset of Alzheimer dementia. Arch Gen Psychiatry 2012; 69(1): 98-106.
[] [PMID: 22213792]
Jack CR Jr, Bennett DA, Blennow K, et al. NIA-AA Research Framework: Toward a biological definition of Alzheimer’s disease. Alzheimers Dement 2018; 14(4): 535-62.
[] [PMID: 29653606]
Wallin AK, Blennow K, Andreasen N, Minthon L. CSF biomarkers for Alzheimer’s Disease: levels of beta-amyloid, tau, phosphorylated tau relate to clinical symptoms and survival. Dement Geriatr Cogn Disord 2006; 21(3): 131-8.
[] [PMID: 16391474]
Boumenir A, Cognat E, Sabia S, et al. CSF level of β-amyloid peptide predicts mortality in Alzheimer’s disease. Alzheimers Res Ther 2019; 11(1): 29.
[] [PMID: 30922415]
Degerman Gunnarsson M, Ingelsson M, Blennow K, Basun H, Lannfelt L, Kilander L. High tau levels in cerebrospinal fluid predict nursing home placement and rapid progression in Alzheimer’s disease. Alzheimers Res Ther 2016; 8(1): 22.
[] [PMID: 27263933]
Wallin AK, Blennow K, Zetterberg H, Londos E, Minthon L, Hansson O. CSF biomarkers predict a more malignant outcome in Alzheimer disease. Neurology 2010; 74(19): 1531-7.
[] [PMID: 20458070]
Degerman Gunnarsson M, Lannfelt L, Ingelsson M, Basun H, Kilander L. High tau levels in cerebrospinal fluid predict rapid decline and increased dementia mortality in Alzheimer’s disease. Dement Geriatr Cogn Disord 2014; 37(3-4): 196-206.
[] [PMID: 24157938]
Nägga K, Wattmo C, Zhang Y, Wahlund LO, Palmqvist S. Cerebral inflammation is an underlying mechanism of early death in Alzheimer’s disease: a 13-year cause-specific multivariate mortality study. Alzheimers Res Ther 2014; 6(4): 41.
[] [PMID: 25435921]
Boström F, Hansson O, Blennow K, et al. Cerebrospinal fluid total tau is associated with shorter survival in dementia with Lewy bodies. Dement Geriatr Cogn Disord 2009; 28(4): 314-9.
[] [PMID: 19844105]
Hertze J, Minthon L, Zetterberg H, Vanmechelen E, Blennow K, Hansson O. Evaluation of CSF biomarkers as predictors of Alzheimer’s disease: a clinical follow-up study of 4.7 years. J Alzheimers Dis 2010; 21(4): 1119-28.
[] [PMID: 21504133]
Folstein MF, Folstein SE, McHugh PR. “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975; 12(3): 189-98.
[] [PMID: 1202204]
Wattmo C, Blennow K, Hansson O. Cerebro-spinal fluid biomarker levels: phosphorylated tau (T) and total tau (N) as markers for rate of progression in Alzheimer’s disease. BMC Neurol 2020; 20(1): 10.
[] [PMID: 31918679]
Wallin AK, Hansson O, Blennow K, Londos E, Minthon L. Can CSF biomarkers or pre-treatment progression rate predict response to cholinesterase inhibitor treatment in Alzheimer’s disease? Int J Geriatr Psychiatry 2009; 24(6): 638-47.
[] [PMID: 19123199]
Frances A. American Psychiatric Association: Diagnostic and statistical manual of mental disorders: DSM-IV Prepared by the Task Force on DSM-IV. 4th ed. Washington, D.C.: American Psychiatric Association 1994.
McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology 1984; 34(7): 939-44.
[] [PMID: 6610841]
Lawton MP, Brody EM. Assessment of older people: self-maintaining and instrumental activities of daily living. Gerontologist 1969; 9(3): 179-86.
[] [PMID: 5349366]
Blennow K, Hampel H, Weiner M, Zetterberg H. Cerebrospinal fluid and plasma biomarkers in Alzheimer disease. Nat Rev Neurol 2010; 6(3): 131-44.
[] [PMID: 20157306]
Olsson A, Vanderstichele H, Andreasen N, et al. Simultaneous measurement of β-amyloid(1-42), total tau, and phosphorylated tau (Thr181) in cerebrospinal fluid by the xMAP technology. Clin Chem 2005; 51(2): 336-45.
[] [PMID: 15563479]
Andreasen N, Minthon L, Clarberg A, et al. Sensitivity, specificity, and stability of CSF-tau in AD in a community-based patient sample. Neurology 1999; 53(7): 1488-94.
[] [PMID: 10534256]
Bouwman FH, van der Flier WM, Schoonenboom NS, et al. Longitudinal changes of CSF biomarkers in memory clinic patients. Neurology 2007; 69(10): 1006-11.
[] [PMID: 17785669]
Kanai M, Matsubara E, Isoe K, et al. Longitudinal study of cerebrospinal fluid levels of tau, A β1-40, and A β1-42(43) in Alzheimer’s disease: a study in Japan. Ann Neurol 1998; 44(1): 17-26.
[] [PMID: 9667589]
Sutphen CL, McCue L, Herries EM, et al. Longitudinal decreases in multiple cerebrospinal fluid biomarkers of neuronal injury in symptomatic late onset Alzheimer’s disease. Alzheimers Dement 2018; 14(7): 869-79.
[] [PMID: 29580670]
Stern Y, Albert S, Tang MX, Tsai WY. Rate of memory decline in AD is related to education and occupation: cognitive reserve? Neurology 1999; 53(9): 1942-7.
[] [PMID: 10599762]
Rhodius-Meester HFM, Liedes H, Koene T, et al. Disease-related determinants are associated with mortality in dementia due to Alzheimer’s disease. Alzheimers Res Ther 2018; 10(1): 23.
[] [PMID: 29458426]
Parsaik AK, Mascarenhas SS, Khosh-Chashm D, et al. Mortality associated with anxiolytic and hypnotic drugs-A systematic review and meta-analysis. Aust N Z J Psychiatry 2016; 50(6): 520-33.
[] [PMID: 26590022]
Zekry D, Herrmann FR, Graf CE, et al. High levels of comorbidity and disability cancel out the dementia effect in predictions of long-term mortality after discharge in the very old. Dement Geriatr Cogn Disord 2011; 32(2): 103-10.
[] [PMID: 21952417]
Holm S, Liss PE, Norheim OF. Access to health care in the Scandinavian countries: ethical aspects. Health Care Anal 1999; 7(4): 321-30.
[] [PMID: 10787795]

© 2022 Bentham Science Publishers | Privacy Policy