Alexander Koppara1,2, Steffen Wolfsgruber1,2, Luca Kleineidam1,2, Klaus Schmidtke3, Lutz Frölich4, Alexander Kurz5, Stefanie Schulz6, Harald Hampel7, Isabella Heuser8, Oliver Peters8, Friedel M Reischies8, Holger Jahn9, Christian Luckhaus10, Michael Hüll11, Hermann-Josef Gertz12, Johannes Schröder13, Johannes Pantel14, Otto Rienhoff15, Eckart Rüther16, Fritz Henn17, Jens Wiltfang16, Wolfgang Maier1,2, Frank Jessen1,2,18, Johannes Kornhuber19, Michael Wagner1,2. 1. Department of Psychiatry, University of Bonn, Germany. 2. German Center for Neurodegenerative Diseases, Bonn, Germany. 3. Center for Geriatric Medicine, Ortenau Klinikum, Offenburg-Gengenbach, Germany. 4. Department of Gerontopsychiatry, Central Institute of Mental Health, Mannheim, Germany. 5. Department of Psychiatry, Technical University of Munich, Germany. 6. Department of Neurology, University of Aachen, Germany. 7. Department of Neurology, Université Pierre et Marie Curie (Sorbonne), and AXA Research Fund & UPMC Chair, Paris, France. 8. Department of Psychiatry, Charité Berlin, Campus Benjamin Franklin, Berlin, Germany. 9. Department of Psychiatry, University of Hamburg, Germany. 10. Department of Psychiatry, University of Düsseldorf, Germany. 11. Center for Psychiatry, Clinic for Geronto- and Neuropsychiatry Emmendingen and Dep. of Psychiatry, University of Freiburg, Germany. 12. Department of Psychiatry, University of Leipzig, Germany. 13. Section for Geriatric Psychiatry/Institute of Gerontology, University of Heidelberg, Germany. 14. Institute of General Medicine University of Frankfurt, Frankfurt am Main, Germany. 15. Department of Medical Informatics, University of Göttingen, Germany. 16. Department of Psychiatry and Psychotherapy, University of Göttingen, Germany. 17. Ichan School of Medicine at Mt. Sinai, New York, USA. 18. Department of Psychiatry, Medical Faculty University of Cologne, Germany. 19. Department of Psychiatry, Friedrich-Alexander-University Erlangen, Germany.
Abstract
BACKGROUND: The recently proposed latent variable δ is a new tool for dementia case finding. It is built in a structural equation modeling framework of cognitive and functional data and constitutes a novel endophenotype for Alzheimer's disease (AD) research and clinical trials. OBJECTIVE: To investigate the association of δ with AD biomarkers and to compare the prediction of δ with established scales for conversion to dementia in patients with mild cognitive impairment (MCI). METHODS: Using data from a multicenter memory clinic study, we examined the external associations of the latent variable δ and compared δ with well-established cognitive and functional scales and cognitive-functional composite scores. For that purpose, logistic regressions with cerebrospinal fluid (CSF) biomarkers and conversion to dementia as dependent variables were performed with the investigated scores. The models were tested for significant differences. RESULTS: In patients with MCI, δ based on a broad range of cognitive scales (including the ADAS-cog, the MMSE, and the CERAD neuropsychological battery) predicted an abnormal CSF Aβ42/tau ratio indicative of AD (n = 340, AUC = 0.78, p < 0.001), and predicted incident dementia within 1-3 years of follow-up (n = 525, AUC = 0.84, p < 0.001). These associations were generally stronger than for any other scale or cognitive-functional composite examined. Homologs of δ based on reduced test batteries yielded somewhat lower effects. CONCLUSION: These findings support the interpretation of δ as a construct capturing the disease-related "essence" of cognitive and functional impairments in patients with MCI and dementia, and suggest that δ might become an analytical tool for dementia research.
BACKGROUND: The recently proposed latent variable δ is a new tool for dementia case finding. It is built in a structural equation modeling framework of cognitive and functional data and constitutes a novel endophenotype for Alzheimer's disease (AD) research and clinical trials. OBJECTIVE: To investigate the association of δ with AD biomarkers and to compare the prediction of δ with established scales for conversion to dementia in patients with mild cognitive impairment (MCI). METHODS: Using data from a multicenter memory clinic study, we examined the external associations of the latent variable δ and compared δ with well-established cognitive and functional scales and cognitive-functional composite scores. For that purpose, logistic regressions with cerebrospinal fluid (CSF) biomarkers and conversion to dementia as dependent variables were performed with the investigated scores. The models were tested for significant differences. RESULTS: In patients with MCI, δ based on a broad range of cognitive scales (including the ADAS-cog, the MMSE, and the CERAD neuropsychological battery) predicted an abnormal CSF Aβ42/tau ratio indicative of AD (n = 340, AUC = 0.78, p < 0.001), and predicted incident dementia within 1-3 years of follow-up (n = 525, AUC = 0.84, p < 0.001). These associations were generally stronger than for any other scale or cognitive-functional composite examined. Homologs of δ based on reduced test batteries yielded somewhat lower effects. CONCLUSION: These findings support the interpretation of δ as a construct capturing the disease-related "essence" of cognitive and functional impairments in patients with MCI and dementia, and suggest that δ might become an analytical tool for dementia research.
Authors: Samantha E John; Ashita S Gurnani; Cara Bussell; Jessica L Saurman; Jason W Griffin; Brandon E Gavett Journal: Neuropsychology Date: 2016-11 Impact factor: 3.295
Authors: Gonzalo Sánchez-Benavides; Gemma Salvadó; Eider M Arenaza-Urquijo; Oriol Grau-Rivera; Marc Suárez-Calvet; Marta Milà-Alomà; José María González-de-Echávarri; Carolina Minguillon; Marta Crous-Bou; Aida Niñerola-Baizán; Andrés Perissinotti; Juan Domingo Gispert; José Luis Molinuevo Journal: Alzheimers Dement (Amst) Date: 2020-11-11