Cholinergic white matter pathways make a stronger contribution to attention and memory in normal aging than cerebrovascular health and nucleus basalis of Meynert
Milan Nemy,
Nira Cedres,
Michel J. Grothe,
J-Sebastian Muehlboeck,
Olof Lindberg,
Zuzana Nedelska,
Olga Stepankova,
Lenka Vyslouzilova,
Maria Eriksdotter,
José Barroso,
Stefan Teipel,
Eric Westman,
Daniel Ferreira
Affiliations
Milan Nemy
Department of Cybernetics, Faculty of Electrical Engineering, Czech Technical University, Prague, Czech Republic
Nira Cedres
Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Faculty of Psychology, University of La Laguna, La Laguna, Tenerife, Spain
Michel J. Grothe
Clinical Dementia Research Section, German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany
J-Sebastian Muehlboeck
Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden
Olof Lindberg
Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden
Zuzana Nedelska
Memory Clinic, Department of Neurology, Charles University, 2nd Faculty of Medicine and Motol University Hospital, Prague, Czech Republic; Department of Radiology, Mayo Clinic, Rochester, MN, USA
Olga Stepankova
Czech Institute of Informatics, Robotics, and Cybernetics, Czech Technical University, Prague, Czech Republic
Lenka Vyslouzilova
Czech Institute of Informatics, Robotics, and Cybernetics, Czech Technical University, Prague, Czech Republic
Maria Eriksdotter
Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Theme Aging, Karolinska University Hospital, Stockholm, Sweden
José Barroso
Faculty of Psychology, University of La Laguna, La Laguna, Tenerife, Spain
Stefan Teipel
Clinical Dementia Research Section, German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany; Department of Psychosomatic Medicine, University Medicine Rostock, Rostock, Germany
Eric Westman
Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Department of Neuroimaging, Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology, and Neuroscience, King’s College London, London, UK
Daniel Ferreira
Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Faculty of Psychology, University of La Laguna, La Laguna, Tenerife, Spain; Corresponding author. Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, NEO floor 7th, Karolinska Institutet, 141 57, Huddinge, Stockholm, Sweden.
The integrity of the cholinergic system plays a central role in cognitive decline both in normal aging and neurological disorders including Alzheimer’s disease and vascular cognitive impairment. Most of the previous neuroimaging research has focused on the integrity of the cholinergic basal forebrain, or its sub-region the nucleus basalis of Meynert (NBM). Tractography using diffusion tensor imaging data may enable modelling of the NBM white matter projections. We investigated the contribution of NBM volume, NBM white matter projections, small vessel disease (SVD), and age to performance in attention and memory in 262 cognitively normal individuals (39–77 years of age, 53% female). We developed a multimodal MRI pipeline for NBM segmentation and diffusion-based tracking of NBM white matter projections, and computed white matter hypointensities (WM-hypo) as a marker of SVD. We successfully tracked pathways that closely resemble the spatial layout of the cholinergic system as seen in previous post-mortem and DTI tractography studies. We found that high WM-hypo load was associated with older age, male sex, and lower performance in attention and memory. A high WM-hypo load was also associated with lower integrity of the cholinergic system above and beyond the effect of age. In a multivariate model, age and integrity of NBM white matter projections were stronger contributors than WM-hypo load and NBM volume to performance in attention and memory. We conclude that the integrity of NBM white matter projections plays a fundamental role in cognitive aging. This and other modern neuroimaging methods offer new opportunities to re-evaluate the cholinergic hypothesis of cognitive aging.
