Resilience against Alzheimer’s disease pathology and atrophy
Svenningsson, Anna LU
(2024)
In Lund University, Faculty of Medicine Doctoral Dissertation Series
- Abstract
- In Alzheimer’s disease (AD), β-amyloid and tau accumulate in the brain leading to neuronal loss and cognitive decline. The associations between these protein aggregates and their downstream effects are clear but not perfect, with other, largely unknown, factors explaining the discrepancy. This phenomenon has been described within the resilience framework.
We aimed to explore whether demographic factors and biomarkers of different processes in the brain could account for this disconnection between AD pathology, neurodegeneration, and cognitive decline.
In paper I lower cerebrospinal fluid (CSF) Aβ42/Aβ40 and smaller hippocampi were independently associated with worse cognitive function in cognitively unimpaired elderly.... (More) - In Alzheimer’s disease (AD), β-amyloid and tau accumulate in the brain leading to neuronal loss and cognitive decline. The associations between these protein aggregates and their downstream effects are clear but not perfect, with other, largely unknown, factors explaining the discrepancy. This phenomenon has been described within the resilience framework.
We aimed to explore whether demographic factors and biomarkers of different processes in the brain could account for this disconnection between AD pathology, neurodegeneration, and cognitive decline.
In paper I lower cerebrospinal fluid (CSF) Aβ42/Aβ40 and smaller hippocampi were independently associated with worse cognitive function in cognitively unimpaired elderly. Age moderated the association for hippocampal volume, with a stronger correlation at higher ages. In paper II CSF biomarkers of axonal degeneration and amyloid pathology were independently associated with rate of cognitive decline when accounting for cortical atrophy in cognitively unimpaired elderly. In paper III education level and age moderated the association between tau burden and cognitive decline in patients with symptomatic AD, such that with advancing tau pathology higher education and higher age were associated with faster cognitive decline. In paper IV the negative effects of tau pathology on brain structure and cognition were exacerbated at higher levels of CSF biomarkers of inflammation and loss of vascular and axonal integrity, with differential associations at different clinical stages of the disease.
The associations for AD pathology with neurodegeneration and cognitive decline are moderated by age, education level, and biomarkers of neuroinflammation and loss of vascular and axonal integrity, and these moderation effects differ between disease stages. This could be interpreted within the resilience framework as these factors influence how well a person can cope with the disease. This has implications for our understanding of cognitive heterogeneity in AD and for identifying factors that prevent or delay clinical manifestations of the disease. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/8773495e-1d3a-455a-b0d7-cf217d934319
- author
- Svenningsson, Anna
LU
- supervisor
-
- Oskar Hansson LU
- Erik Stomrud LU
- Sebastian Palmqvist LU
- Rik Ossenkoppele LU
- opponent
-
- professor Selbæk, Geir, Oslo University
- organization
- publishing date
- 2024
- type
- Thesis
- publication status
- published
- subject
- keywords
- Alzheimer's disease, atrophy, cognitive resilience, brain resilience, cognitive reserve, brain reserve
- in
- Lund University, Faculty of Medicine Doctoral Dissertation Series
- issue
- 2024:96
- pages
- 94 pages
- publisher
- Lund University, Faculty of Medicine
- defense location
- Segerfalksalen, BMC A10, Sölvegatan 17 i Lund. Join by Zoom: https://lu-se.zoom.us/j/63711511140
- defense date
- 2024-09-06 09:00:00
- ISSN
- 1652-8220
- ISBN
- 978-91-8021-592-3
- language
- English
- LU publication?
- yes
- id
- 8773495e-1d3a-455a-b0d7-cf217d934319
- date added to LUP
- 2024-08-09 14:33:57
- date last changed
- 2025-04-04 14:19:55
@phdthesis{8773495e-1d3a-455a-b0d7-cf217d934319,
abstract = {{In Alzheimer’s disease (AD), β-amyloid and tau accumulate in the brain leading to neuronal loss and cognitive decline. The associations between these protein aggregates and their downstream effects are clear but not perfect, with other, largely unknown, factors explaining the discrepancy. This phenomenon has been described within the resilience framework.<br/><br/>We aimed to explore whether demographic factors and biomarkers of different processes in the brain could account for this disconnection between AD pathology, neurodegeneration, and cognitive decline.<br/><br/>In paper I lower cerebrospinal fluid (CSF) Aβ42/Aβ40 and smaller hippocampi were independently associated with worse cognitive function in cognitively unimpaired elderly. Age moderated the association for hippocampal volume, with a stronger correlation at higher ages. In paper II CSF biomarkers of axonal degeneration and amyloid pathology were independently associated with rate of cognitive decline when accounting for cortical atrophy in cognitively unimpaired elderly. In paper III education level and age moderated the association between tau burden and cognitive decline in patients with symptomatic AD, such that with advancing tau pathology higher education and higher age were associated with faster cognitive decline. In paper IV the negative effects of tau pathology on brain structure and cognition were exacerbated at higher levels of CSF biomarkers of inflammation and loss of vascular and axonal integrity, with differential associations at different clinical stages of the disease.<br/><br/>The associations for AD pathology with neurodegeneration and cognitive decline are moderated by age, education level, and biomarkers of neuroinflammation and loss of vascular and axonal integrity, and these moderation effects differ between disease stages. This could be interpreted within the resilience framework as these factors influence how well a person can cope with the disease. This has implications for our understanding of cognitive heterogeneity in AD and for identifying factors that prevent or delay clinical manifestations of the disease.}},
author = {{Svenningsson, Anna}},
isbn = {{978-91-8021-592-3}},
issn = {{1652-8220}},
keywords = {{Alzheimer's disease; atrophy; cognitive resilience; brain resilience; cognitive reserve; brain reserve}},
language = {{eng}},
number = {{2024:96}},
publisher = {{Lund University, Faculty of Medicine}},
school = {{Lund University}},
series = {{Lund University, Faculty of Medicine Doctoral Dissertation Series}},
title = {{Resilience against Alzheimer’s disease pathology and atrophy}},
url = {{https://lup.lub.lu.se/search/files/192836934/Thesis_summary_Anna_Svenningsson.pdf}},
year = {{2024}},
}