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Journal article
Association of Basal Forebrain Atrophy With Cognitive Decline in Early Alzheimer Disease
Neurology, Vol.103(2), e209626
2024
Abstract
Background and Objectives
In early Alzheimer disease (AD), β-amyloid (Aβ) deposition is associated with volume loss in the basal forebrain (BF) and cognitive decline. However, the extent to which Aβ-related BF atrophy manifests as cognitive decline is not understood. This study sought to characterize the relationship between BF atrophy and the decline in memory and attention in patients with early AD.
Methods
Participants from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study who completed Aβ-PET imaging and repeated MRI and cognitive assessments were included. At baseline, participants were classified based on their clinical dementia stage and Aβ status, yielding groups that were cognitively unimpaired (CU) Aβ−, CU Aβ+, and mild cognitive impairment (MCI) Aβ+. Linear mixed-effects models were used to assess changes in volumetric measures of BF subregions and the hippocampus and changes in AIBL memory and attention composite scores for each group compared with CU Aβ− participants. Associations between Aβ burden, brain atrophy, and cognitive decline were evaluated and explored further using mediation analyses.
Results
The cohort included 476 participants (72.6 ± 5.9 years, 55.0% female) with longitudinal data from a median follow-up period of 6.1 years. Compared with the CU Aβ− group (n = 308), both CU Aβ+ (n = 107) and MCI Aβ+ (n = 61) adults showed faster decline in BF and hippocampal volumes and in memory and attention (Cohen d = 0.73–1.74). Rates of atrophy in BF subregions and the hippocampus correlated with cognitive decline, and each individually mediated the impact of Aβ burden on memory and attention decline. When all mediators were considered simultaneously, hippocampal atrophy primarily influenced the effect of Aβ burden on memory decline (β [SE] = −0.139 [0.032], proportion mediated [PM] = 28.0%) while the atrophy of the posterior nucleus basalis of Meynert in the BF (β [SE] = −0.068 [0.029], PM = 13.1%) and hippocampus (β [SE] = −0.121 [0.033], PM = 23.4%) distinctively influenced Aβ-related attention decline.
Discussion
These findings highlight the significant role of BF atrophy in the complex pathway linking Aβ to cognitive impairment in early stages of AD. Volumetric assessment of BF subregions could be essential in elucidating the relationships between the brain structure and behavior in AD.
Details
- Title
- Association of Basal Forebrain Atrophy With Cognitive Decline in Early Alzheimer Disease
- Authors/Creators
- Ying Xia - Australian e-Health Research CentreVincent Dore - Australian e-Health Research CentreJurgen Fripp - CSIRO Health and BiosecurityPierrick Bourgeat - CSIRO Health and BiosecuritySimon M. Laws - Edith Cowan UniversityChristopher J. Fowler - Australian e-Health Research CentreStephanie R. Rainey-Smith - Edith Cowan UniversityRalph N. Martins - Edith Cowan University (Australia, Perth)Christopher Rowe - Austin HealthColin L. Masters - Australian e-Health Research CentreElizabeth J. Coulson - Curtin UniversityPaul Maruff - Australian e-Health Research Centre
- Publication Details
- Neurology, Vol.103(2), e209626
- Publisher
- Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology
- Identifiers
- 991005680466907891
- Copyright
- © 2024 The Author(s).
- Murdoch Affiliation
- Health Futures Institute
- Language
- English
- Resource Type
- Journal article
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