Structural equation modeling identifies differential links of pathologies and atrophy in dementia
Poster No:
238
Submission Type:
Abstract Submission
Authors:
Lena Haag1, Elisa Lancini1, Renat Yakupov1, Gabriel Ziegler1, Yeo-Jin Yi1, Glanz Wenzel2, Falk Lüsenbrink1, Oliver Peters3, Eike Spruth4, Slawek Altenstein3, Josef Priller3, Luisa-Sophie Schneider5, Xiao Wang5, Lukas Preis6, Frederic Brosseron7, Nina Roy-Kluth7, Anja Schneider7, Klaus Fliessbach7, Michael Wagner8, Steffen Wolfsgruber8, Jens Wiltfang9, Niels Hansen10, Ayda Rostamzadeh11, Michael Ewers12, Katharina Buerger13, Robert Perneczky13, Daniel Janowitz14, Boris-Stephan Rauchmann15, Stefan Teipel16, Ingo Kilimann17, Doreen Goerss18, Christoph Laske19, Matthias Munk20, Michael Heneka21, Peter Dechent22, Stefan Hetzer5, Klaus Scheffler23, Emrah Düzel24, Matthew Betts25, Dorothea Hämmerer26
Institutions:
1Institute of Cognitive Neurology and Dementia Research (IKND), Magdeburg, Germany, 2German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany, 3German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany, 4Department of Psychiatry and Psychotherapy, Charité, Berlin, Germany, 5Charité – Universitätsmedizin Berlin, Berlin, Germany, 6Charité – Universitätsmedizin Berlin - Institute of Psychiatry and Psychotherapy, Berlin, Germany, 7German Centre for Neurodegenerative Diseases (DZNE), Bonn, Germany, 8German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany, 9Department of Psychiatry and Psychotherapy, Medical University Göttingen, Göttingen, Lower Saxony, 10University of Goettingen, Goettingen, Germany, 11University of Cologne, Cologne, Germany, 12Institute for Stroke and Dementia Research, Munich, Bavaria, 13German Centre for Neurodegenerative Diseases (DZNE), Munich, Germany, 14University Hospital, LMU Munich, Munich, Germany, 15University Hospital, LMU Munich, München, Deutschland, 16Rostock University Medical Center & German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany, 17German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany, 18Rostock University Medical Center, Rostock, Germany, 19German Centre for Neurodegenerative Diseases (DZNE), Tübingen, Germany, 20German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany, 21University of Luxembourg, Luxembourg, Luxembourg, 22Georg-August-University Goettingen, Göttingen, Germany, 23University of Tübingen, Tübingen, Germany, 24Institute of Cognitive Neurology and Dementia Research, Magdeburg, Germany, 25German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Sachsen-Anhalt, 26Innsbruck University, Innsbruck, Tirol
First Author:
Co-Author(s):
Lukas Preis
Charité – Universitätsmedizin Berlin - Institute of Psychiatry and Psychotherapy
Berlin, Germany
Charité – Universitätsmedizin Berlin - Institute of Psychiatry and Psychotherapy
Berlin, Germany
Jens Wiltfang
Department of Psychiatry and Psychotherapy, Medical University Göttingen
Göttingen, Lower Saxony
Department of Psychiatry and Psychotherapy, Medical University Göttingen
Göttingen, Lower Saxony
Stefan Teipel
Rostock University Medical Center & German Center for Neurodegenerative Diseases (DZNE)
Rostock, Germany
Rostock University Medical Center & German Center for Neurodegenerative Diseases (DZNE)
Rostock, Germany
Introduction:
Our main source of noradrenaline in the cortex is the locus coeruleus, a brainstem nucleus which is amongst the brain structures affected earliest by Alzheimer's disease-related tau pathology (Braak et al., 2011). Since intact noradrenergic modulation has been linked to cognitive reserve in ageing (Wilson et al., 2013), interindividual differences in the integrity of cortical noradrenaline-projection regions could be an important neural resource for cognitive reserve in ageing. The aim of this study was to determine whether volumes of brain areas known to be rich in noradrenergic receptors and transporters are relatively preserved in individuals with lower levels of Alzheimer's disease pathology.
Methods:
Based on prior work on NA receptor and transporter distribution (Palomero-Gallagher et al., 2015), we distinguished between 'areas high in noradrenaline' and 'areas low in noradrenaline' and compared differential associations of atrophy in those areas with CSF amyloid-ß 42/40, CSF phosphorylated tau protein, and memory function across healthy controls (n = 122), subjects with subjective cognitive decline (n = 156) and patients with mild cognitive impairment or mild Alzheimer's disease dementia (n = 126). Analyses were carried out with structural equation modeling which allows to assess the interrelations between multiple variables while testing for group differences in these interrelations.
Results:
Our analyses confirmed that regional brain volumes in 'areas high in NA' vs. 'areas low in NA' are differentially related to AD pathology markers. Only 'areas high in noradrenaline' were related to disease markers. Across all groups, atrophy in 'areas high in noradrenaline' were linked to worse memory. Moreover, groups differed in their links between atrophy in 'areas high in noradrenaline' and amyloid levels or memory capacity. In subjects with subjective cognitive decline, higher amyloid pathology predicted atrophy in 'areas high in noradrenaline' (ß = 0.343), while in patients with mild cognitive impairment and Alzheimer's disease, higher amyloid pathology was associated with memory impairment (ß = 0.295). The study also found that CSF amyloid and tau biomarkers were less correlated in the subjective cognitive decline (ß = -0.366) as compared to the mild cognitive impairment/Alzheimer's disease groups (ß = -0.424), suggesting distinguishable interrelatedness of amyloid and tau after early disease onset.
·Whole sample model. (Red: negative links; green: positive links, amyloid pathology is inversely coded).
Conclusions:
In summary, we showed differential links of high and low noradrenergic-projection cortical regions with Alzheimer's disease pathologies and cognitive function, indicating the relevance of considering the noradrenergic system as a protective factor in the ageing brain. Moreover, differential relationships between risk factors and their effect on areas high and low in noradrenaline in populations across the Alzheimer spectrum highlight the relevance of using analyses methods able to capture subgroup specific links between risk factors and brain atrophy in ageing.
Disorders of the Nervous System:
Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s) 1
Lifespan Development:
Aging
Modeling and Analysis Methods:
Segmentation and Parcellation
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
Transmitter Systems 2
Novel Imaging Acquisition Methods:
Anatomical MRI
Keywords:
Aging
Memory
Noradrenaline
Statistical Methods
STRUCTURAL MRI
1|2Indicates the priority used for review
Provide references using author date format
Palomero-Gallagher, N., Amunts, K., Zilles, K., 2015. Transmitter Receptor Distribution in the Human Brain, in: Brain Mapping. Elsevier, pp. 261–275. https://doi.org/10.1016/B978-0-12-397025-1.00221-9
Wilson, R.S., Nag, S., Boyle, P.A., Hizel, L.P., Yu, L., Buchman, A.S., Schneider, J.A., Bennett, D.A., 2013. Neural reserve, neuronal density in the locus ceruleus, and cognitive decline. Neurology 80, 1202–1208.