Journal
NEUROIMAGE
Volume 211, Issue -, Pages -Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.neuroimage.2020.116607
Keywords
Cholinergic system; Basal forebrain; Normal aging; Small vessel disease; Cognition; Magnetic resonance imaging
Funding
- Fundacion Canaria Dr. Manuel Morales
- Fundacion Cajacanarias
- Swedish Foundation for Strategic Research (SSF)
- Strategic Research Programme in Neuroscience at Karolinska Institutet (StratNeuro)
- Swedish Research Council (VR)
- Ake Wiberg foundation
- Hjarnfonden
- Alzheimerfonden
- Demensfonden Stiftelsen Olle Engkvist Byggmastare
- Birgitta och Sten Westerberg
- Alderssjukdomar
- Gun and Bertil Stohnes
- Sigurd och Elsa Goljes Minne
- Gamla Tjanarinnor
- Karolinska Institutet Forskningstiftelse
- Demensforbundet
- Grant Agency of the Czech Technical University in Prague [SGS19/111/OHK4/2T/13]
- Czech Alzheimer Foundation
- IBRO-ISN fellowship 2018
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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.
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