Longitudinal trajectories of basal forebrain volume in normal aging and Alzheimer's disease

Ying Xia; Paul Maruff; Vincent Doré; Pierrick Bourgeat; Simon M Laws; Christopher Fowler; Stephanie R Rainey-Smith; Ralph N Martins; Victor L Villemagne; Christopher C Rowe; Colin L Masters; Elizabeth J Coulson; Jurgen Fripp

doi:10.1016/j.neurobiolaging.2023.09.002

Longitudinal trajectories of basal forebrain volume in normal aging and Alzheimer's disease

Neurobiol Aging. 2023 Dec:132:120-130. doi: 10.1016/j.neurobiolaging.2023.09.002. Epub 2023 Sep 11.

Authors

Affiliations

¹ The Australian e-Health Research Centre, CSIRO Health and Biosecurity, Brisbane, Queensland, Australia. Electronic address: ying.xia@csiro.au.
² Cogstate Ltd, Melbourne, Victoria, Australia; The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia.
³ Department of Nuclear Medicine and Centre for PET, Austin Health, Melbourne, Victoria, Australia; The Australian e-Health Research Centre, CSIRO Health and Biosecurity, Melbourne, Victoria, Australia.
⁴ The Australian e-Health Research Centre, CSIRO Health and Biosecurity, Brisbane, Queensland, Australia.
⁵ Collaborative Genomics and Translation Group, School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, Australia; Centre for Precision Health, Edith Cowan University, Joondalup, Western Australia, Australia; Curtin Medical School, Curtin University, Bentley, Western Australia, Australia.
⁶ The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia.
⁷ Centre for Healthy Ageing, Health Futures Institute, Murdoch University, Murdoch, Western Australia, Australia; Australian Alzheimer's Research Foundation, Sarich Neuroscience Research Institute, Nedlands, Western Australia, Australia; School of Psychological Science, University of Western Australia, Crawley, Western Australia, Australia; School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, Australia.
⁸ Australian Alzheimer's Research Foundation, Sarich Neuroscience Research Institute, Nedlands, Western Australia, Australia; School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, Australia; Department of Biomedical Sciences, Macquarie University, Sydney, New South Wales, Australia.
⁹ Department of Nuclear Medicine and Centre for PET, Austin Health, Melbourne, Victoria, Australia; Centre for Precision Health, Edith Cowan University, Joondalup, Western Australia, Australia; Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
¹⁰ Department of Nuclear Medicine and Centre for PET, Austin Health, Melbourne, Victoria, Australia; Florey Department of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia.
¹¹ Queensland Brain Institute, The University of Queensland, Brisbane, Queensland, Australia; School of Biomedical Sciences, The University of Queensland, Brisbane, Queensland, Australia.

PMID: 37801885
DOI: 10.1016/j.neurobiolaging.2023.09.002

Abstract

Dysfunction of the cholinergic basal forebrain (BF) system and amyloid-β (Aβ) deposition are early pathological features in Alzheimer's disease (AD). However, their association in early AD is not well-established. This study investigated the nature and magnitude of volume loss in the BF, over an extended period, in 516 older adults who completed Aβ-PET and serial magnetic resonance imaging scans. Individuals were grouped at baseline according to the presence of cognitive impairment (CU, CI) and Aβ status (Aβ-, Aβ+). Longitudinal volumetric changes in the BF and hippocampus were assessed across groups. The results indicated that high Aβ levels correlated with faster volume loss in the BF and hippocampus, and the effect of Aβ varied within BF subregions. Compared to CU Aβ+ individuals, Aβ-related loss among CI Aβ+ adults was much greater in the predominantly cholinergic subregion of Ch4p, whereas no difference was observed for the Ch1/Ch2 region. The findings support early and substantial vulnerability of the BF and further reveal distinctive degeneration of BF subregions during early AD.

Keywords: Alzheimer’s disease; Amyloid-β; Basal forebrain; Longitudinal; Magnetic resonance imaging.

MeSH terms

Aged
Aging / pathology
Alzheimer Disease* / diagnostic imaging
Alzheimer Disease* / pathology
Amyloid beta-Peptides
Basal Forebrain* / diagnostic imaging
Basal Forebrain* / pathology
Cholinergic Agents
Cognitive Dysfunction* / diagnostic imaging
Cognitive Dysfunction* / pathology
Humans
Magnetic Resonance Imaging
Positron-Emission Tomography

Substances

Amyloid beta-Peptides
Cholinergic Agents