Prevalence of abnormal Alzheimer's disease biomarkers in patients with subjective cognitive decline: cross-sectional comparison of three European memory clinic samples.
Wolfsgruber, Steffen; Molinuevo, José Luis; Wagner, Michaelet al.
2019 • In Alzheimer's Research and Therapy, 11 (1), p. 8
[en] [en] INTRODUCTION: Subjective cognitive decline (SCD) in cognitively unimpaired older individuals has been recognized as an early clinical at-risk state for Alzheimer's disease (AD) dementia and as a target population for future dementia prevention trials. Currently, however, SCD is heterogeneously defined across studies, potentially leading to variations in the prevalence of AD pathology. Here, we compared the prevalence and identified common determinants of abnormal AD biomarkers in SCD across three European memory clinics participating in the European initiative on harmonization of SCD in preclinical AD (Euro-SCD).
METHODS: We included three memory clinic SCD samples with available cerebrospinal fluid (CSF) biomaterial (IDIBAPS, Barcelona, Spain, n = 44; Amsterdam Dementia Cohort (ADC), The Netherlands, n = 50; DELCODE multicenter study, Germany, n = 42). CSF biomarkers (amyloid beta (Aβ)42, tau, and phosphorylated tau (ptau181)) were centrally analyzed in Amsterdam using prespecified cutoffs to define prevalence of pathological biomarker concentrations. We used logistic regression analysis in the combined sample across the three centers to investigate center effects with regard to likelihood of biomarker abnormality while taking potential common predictors (e.g., age, sex, apolipoprotein E (APOE) status, subtle cognitive deficits, depressive symptoms) into account.
RESULTS: The prevalence of abnormal Aβ42, but not tau or ptau181, levels was different across centers (64% DELCODE, 57% IDIBAPS, 22% ADC; p < 0.001). Logistic regression analysis revealed that the likelihood of abnormal Aβ42 (and also abnormal tau or ptau181) levels was predicted by age and APOE status. For Aβ42 abnormality, we additionally observed a center effect, indicating between-center heterogeneity not explained by age, APOE, or the other included covariates.
CONCLUSIONS: While heterogeneous frequency of abnormal Aβ42 was partly explained by between-sample differences in age range and APOE status, the additional observation of center effects indicates between-center heterogeneity that may be attributed to different recruitment procedures. These findings highlight the need for the development of harmonized recruitment protocols for SCD case definition in multinational studies to achieve similar enrichment rates of preclinical AD.
Disciplines :
Neurology
Author, co-author :
Wolfsgruber, Steffen ; Department of Neurodegeneration and Geriatric Psychiatry, University Hospital Bonn, Bonn, Germany. Steffen.Wolfsgruber@dzne.de ; German Center for Neurodegenerative Diseases, Sigmund-Freud-Straße 27, 53127, Bonn, Germany. Steffen.Wolfsgruber@dzne.de
Molinuevo, José Luis; Alzheimer's Disease and Other Cognitive Disorders Unit, IDIBAPS, Hospital Clinic, Barcelona, Spain ; BarcelonaBeta Brain Research Center, Fundació Pasqual Maragall, Pompeu Fabra University, Barcelona, Spain
Wagner, Michael; Department of Neurodegeneration and Geriatric Psychiatry, University Hospital Bonn, Bonn, Germany ; German Center for Neurodegenerative Diseases, Sigmund-Freud-Straße 27, 53127, Bonn, Germany
Teunissen, Charlotte E; Neurochemistry Lab and Biobank, Department of Clinical Chemistry, Amsterdam Neuroscience, Amsterdam University Medical Centers, Amsterdam, The Netherlands
Rami, Lorena; Alzheimer's Disease and Other Cognitive Disorders Unit, IDIBAPS, Hospital Clinic, Barcelona, Spain
Coll-Padrós, Nina; Alzheimer's Disease and Other Cognitive Disorders Unit, IDIBAPS, Hospital Clinic, Barcelona, Spain
Bouwman, Femke H; Alzheimer Center and Department of Neurology, Neuroscience Campus Amsterdam, Amsterdam University Medical Centers, Amsterdam, The Netherlands
Slot, Rosalinde E R; Alzheimer Center and Department of Neurology, Neuroscience Campus Amsterdam, Amsterdam University Medical Centers, Amsterdam, The Netherlands
Wesselman, Linda M P; Alzheimer Center and Department of Neurology, Neuroscience Campus Amsterdam, Amsterdam University Medical Centers, Amsterdam, The Netherlands
Peters, Oliver; Department of Psychiatry and Psychotherapy, Charité, Campus Benjamin Franklin, Berlin, Germany
Luther, Katja; Department of Psychiatry and Psychotherapy, Charité, Campus Benjamin Franklin, Berlin, Germany
Buerger, Katharina; Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität, Munich, Germany ; German Center for Neurodegenerative Diseases, Munich, Germany
Priller, Josef; Department of Neuropsychiatry, Charité-Universitaetsmedizin Berlin, Berlin, Germany
Laske, Christoph; Department of Psychiatry and Psychotherapy, University of Tübingen, Tübingen, Germany ; German Center for Neurodegenerative Diseases, Tübingen, Germany
Teipel, Stefan; German Center for Neurodegenerative Diseases, Rostock, Germany
Spottke, Annika; German Center for Neurodegenerative Diseases, Sigmund-Freud-Straße 27, 53127, Bonn, Germany
HENEKA, Michael ; Department of Neurodegeneration and Geriatric Psychiatry, University Hospital Bonn, Bonn, Germany ; German Center for Neurodegenerative Diseases, Sigmund-Freud-Straße 27, 53127, Bonn, Germany
Düzel, Emrah; German Center for Neurodegenerative Diseases, Magdeburg, Germany
Drzezga, Alexander; Department of Nuclear Medicine, Medical Faculty, University of Cologne, Cologne, Germany
Wiltfang, Jens; German Center for Neurodegenerative Diseases (DZNE), Goettingen, Germany ; Department of Psychiatry and Psychotherapy, University Medical Center Goettingen, Goettingen, Germany ; iBiMED, Medical Sciences Department, University of Aveiro, Aveiro, Portugal
Sikkes, Sietske A M; Department of Epidemiology and Biostatistics, Amsterdam University Medical Centers, Amsterdam, The Netherlands ; Massachusetts General Hospital, Department of Neurology / Harvard Medical School, Boston, USA
van der Flier, Wiesje M; Alzheimer Center and Department of Neurology, Neuroscience Campus Amsterdam, Amsterdam University Medical Centers, Amsterdam, The Netherlands ; Department of Epidemiology and Biostatistics, Amsterdam University Medical Centers, Amsterdam, The Netherlands
Jessen, Frank; German Center for Neurodegenerative Diseases, Sigmund-Freud-Straße 27, 53127, Bonn, Germany ; Department of Psychiatry, Medical Faculty, University of Cologne, Cologne, Germany
Prevalence of abnormal Alzheimer's disease biomarkers in patients with subjective cognitive decline: cross-sectional comparison of three European memory clinic samples.
This work was supported by an EU Joint Program Neurodegenerative Disease Research (JPND) project (grant number JPND_PS_FP-689-019). The project is supported through the following funding organizations under the aegis of JPND (www.jpnd.eu): Germany, Bundesministerium für Bildung und Forschung (BMBF grant number 01ED1508); The Netherlands Organisation for Health Research and Development; Spain, Instituto De Salud Carlos III. This research was also supported by the German Research Council (DFG; grant number JE 2707/7–1) and the German Center for Neurodegenerative Diseases (Deutsches Zentrum für Neurodegenerative Erkrankungen; DZNE; reference number BN012) (DELCODE). WMvdF is the recipient of a research grant on subjective cognitive decline (SCIENCe project: Gieskes Strijbis fonds). Prof Jens Wiltfang is supported by an Ilídio Pinho professorship and iBiMED (UID/BIM/ 04501/2013), and FCT project PTDC/DTP_PIC/5587/2014 at the University of Aveiro, Portugal.
Andrieu S, Coley N, Lovestone S, Aisen PS, Vellas B. Prevention of sporadic Alzheimer's disease: lessons learned from clinical trials and future directions. Lancet Neurol. 2015;14:926-44. https://doi.org/10.1016/S1474-4422(15)00153-2.
Vellas B, Aisen PS, Sampaio C, Carrillo M, Scheltens P, Scherrer B, et al. Prevention trials in Alzheimer's disease: an EU-US task force report. Prog Neurobiol. 2011;95:594-600. https://doi.org/10.1016/j.pneurobio.2011.08.014.
Jack CR, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB, et al. NIA-AA research framework: toward a biological definition of Alzheimer's disease. Alzheimers Dement. 2018;14:535-62. https://doi.org/10.1016/j.jalz.2018.02.018.
Jessen F, Amariglio RE, van Boxtel M, Breteler M, Ceccaldi M, Chételat G, et al. A conceptual framework for research on subjective cognitive decline in preclinical Alzheimer's disease. Alzheimers Dement. 2014;10:844-52. https://doi.org/10.1016/j.jalz.2014.01.001.
Molinuevo JL, Rabin LA, Amariglio R, Buckley R, Dubois B, Ellis KA, et al. Implementation of subjective cognitive decline criteria in research studies. Alzheimers Dement. 2017;13:296-311. https://doi.org/10.1016/j.jalz.2016.09.012.
van der Flier WM, Pijnenburg YAL, Prins N, Lemstra AW, Bouwman FH, Teunissen CE, et al. Optimizing patient care and research: the Amsterdam Dementia Cohort. J Alzheimers Dis. 2014;41:313-27. https://doi.org/10.3233/JAD-132306.
van der Flier WM, Scheltens P. Amsterdam Dementia Cohort: performing research to optimize care. J Alzheimers Dis. 2018;62:1091-111. https://doi.org/10.3233/JAD-170850.
Sierra-Rio A, Balasa M, Olives J, Antonell A, Iranzo A, Castellví M, et al. Cerebrospinal fluid biomarkers predict clinical evolution in patients with subjective cognitive decline and mild cognitive impairment. Neurodegener Dis. 2016;16:69-76. https://doi.org/10.1159/000439258.
Jessen F, Spottke A, Boecker H, Brosseron F, Buerger K, Catak C, et al. Design and first baseline data of the DZNE multicenter observational study on predementia Alzheimer's disease (DELCODE). Alzheimers Res Ther. 2018;10:15. https://doi.org/10.1186/s13195-017-0314-2.
Thalmann B, Monsch AU, Schneitter M, Bernasconi F, Aebi C, Camachova-Davet Z, et al. The CERAD neuropsychological assessment battery (CERAD-NAB) - a minimal data set as a common tool for German-speaking Europe. Neurobiol Aging. 2000;21:30.
Reitan RM. Validity of the Trail Making Test as an indicator of organic brain damage. Percept Mot Skills. 1958;8:271-6.
Berres M, Monsch AU, Bernasconi F, Thalmann B, Stähelin HB. Normal ranges of neuropsychological tests for the diagnosis of Alzheimer's disease. Stud Health Technol Inform. 2000;77:195-9.
Petersen RC, Smith GE, Waring SC, Ivnik RJ, Tangalos EG, Kokmen E. Mild cognitive impairment: clinical characterization and outcome. Arch Neurol. 1999;56:303-8.
Rami L, Molinuevo JL, Sanchez-Valle R, Bosch B, Villar A. Screening for amnestic mild cognitive impairment and early Alzheimer's disease with M@T (Memory Alteration Test) in the primary care population. Int J Geriatr Psychiatry. 2007;22:294-304. https://doi.org/10.1002/gps.1672.
del Campo M, Mollenhauer B, Bertolotto A, Engelborghs S, Hampel H, Simonsen AH, et al. Recommendations to standardize preanalytical confounding factors in Alzheimer's and Parkinson's disease cerebrospinal fluid biomarkers: an update. Biomark Med. 2012;6:419-30. https://doi.org/10.2217/bmm.12.46.
Bertens D, Tijms BM, Scheltens P, Teunissen CE, Visser PJ. Unbiased estimates of cerebrospinal fluid β-amyloid 1-42 cutoffs in a large memory clinic population. Alzheimers Res Ther. 2017;9:8. https://doi.org/10.1186/s13195-016-0233-7.
Duits FH, Teunissen CE, Bouwman FH, Visser P, Mattsson N, Zetterberg H, et al. The cerebrospinal fluid «Alzheimer profile»: easily said, but what does it mean? Alzheimers Dement. 2014;10:713-23.e2. https://doi.org/10.1016/j.jalz.2013.12.023.
Rami L, Fortea J, Bosch B, Solé-Padullés C, Lladó A, Iranzo A, et al. Cerebrospinal fluid biomarkers and memory present distinct associations along the continuum from healthy subjects to AD patients. J Alzheimers Dis. 2011;23:319-26. https://doi.org/10.3233/JAD-2010-101422.
Saan RJ, Deelman BG. De 15-woordentest A en B (een voorlopige handleiding). Groningen: Afdeling Neuropsychologie, AZG; 1986.
Peña-Casanova J, Gramunt-Fombuena N, Quiñones-Ubeda S, Sánchez-Benavides G, Aguilar M, Badenes D, et al. Spanish Multicenter Normative Studies (NEURONORMA Project): norms for the Rey-Osterrieth complex figure (copy and memory), and free and cued selective reminding test. Arch Clin Neuropsychol. 2009;24:371-93. https://doi.org/10.1093/arclin/acp041.
Strauss E, Sherman EMS, Spreen O. A compendium of neuropsychological tests: administration, norms, and commentary. Oxford University Press: American Chemical Society; 2006.
Wagner M, Wolf S, Reischies FM, Daerr M, Wolfsgruber S, Jessen F, et al. Biomarker validation of a cued recall memory deficit in prodromal Alzheimer disease. Neurology. 2012;78:379-86. https://doi.org/10.1212/WNL.0b013e318245f447.
Yesavage JA, Sheikh JI. Geriatric depression scale (GDS): recent evidence and development of a shorter version. Clin Gerontol. 1986;5:165-73.
Bjelland I, Dahl AA, Haug TT, Neckelmann D. The validity of the Hospital Anxiety and Depression Scale. An updated literature review. J Psychosom Res. 2002;52:69-77.
Pfeffer RI, Kurosaki TT, Harrah CH, Chance JM, Filos S. Measurement of functional activities in older adults in the community. J Gerontol. 1982;37:323-9.
Gélinas I, Gauthier L, McIntyre M, Gauthier S. Development of a functional measure for persons with Alzheimer's disease: the disability assessment for dementia. Am J Occup Ther. 1999;53:471-81.
Mielke MM, Wiste HJ, Weigand SD, Knopman DS, Lowe VJ, Roberts RO, et al. Indicators of amyloid burden in a population-based study of cognitively normal elderly. Neurology. 2012;79:1570-7. https://doi.org/10.1212/WNL.0b013e31826e2696.
Jessen F, Wolfsgruber S, Wiese B, Bickel H, Mösch E, Kaduszkiewicz H, et al. AD dementia risk in late MCI, in early MCI, and in subjective memory impairment. Alzheimers Dement. 2014;10:76-83.
van Harten AC, Smits LL, Teunissen CE, Visser PJ, Koene T, Blankenstein MA, et al. Preclinical AD predicts decline in memory and executive functions in subjective complaints. Neurology. 2013;81:1409-16.
Willemse EAJ, van Uffelen KWJ, van der Flier WM, Teunissen CE. Effect of long-term storage in biobanks on cerebrospinal fluid biomarker Aβ1-42, T-tau, and P-tau values. Alzheimers Dement (Amst). 2017;8:45-50. https://doi.org/10.1016/j.dadm.2017.03.005.
Jutten RJ, Peeters CFW, Leijdesdorff SMJ, Visser PJ, Maier AB, Terwee CB, et al. Detecting functional decline from normal aging to dementia: development and validation of a short version of the Amsterdam IADL Questionnaire. Alzheimers Dement (Amst). 2017;8:26-35.
Papp KV, Amariglio RE, Mormino EC, Hedden T, Dekhytar M, Johnson KA, et al. Free and cued memory in relation to biomarker-defined abnormalities in clinically normal older adults and those at risk for Alzheimer's disease. Neuropsychologia. 2015;73:169-75. https://doi.org/10.1016/j.neuropsychologia.2015.04.034.
Papp KV, Mormino EC, Amariglio RE, Munro C, Dagley A, Schultz AP, et al. Biomarker validation of a decline in semantic processing in preclinical Alzheimer's disease. Neuropsychology. 2016;30:624-30. https://doi.org/10.1037/neu0000246.
