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How Do Modifiable Risk Factors Affect Alzheimer's Disease Pathology or Mitigate Its Effect on Clinical Symptom Expression?

Ourry, Valentin ; Binette, Alexa Pichet LU ; St-Onge, Frédéric ; Strikwerda-Brown, Cherie ; Chagnot, Audrey ; Poirier, Judes ; Breitner, John ; Arenaza-Urquijo, Eider M. ; Rabin, Jennifer S. and Buckley, Rachel , et al. (2023) In Biological Psychiatry
Abstract

Epidemiological studies show that modifiable risk factors account for approximately 40% of the population variability in risk of developing dementia, including sporadic Alzheimer's disease (AD). Recent findings suggest that these factors may also modify disease trajectories of people with autosomal-dominant AD. With positron emission tomography imaging, it is now possible to study the disease many years before its clinical onset. Such studies can provide key knowledge regarding pathways for either the prevention of pathology or the postponement of its clinical expression. The former “resistance pathway” suggests that modifiable risk factors could affect amyloid and tau burden decades before the appearance of cognitive impairment.... (More)

Epidemiological studies show that modifiable risk factors account for approximately 40% of the population variability in risk of developing dementia, including sporadic Alzheimer's disease (AD). Recent findings suggest that these factors may also modify disease trajectories of people with autosomal-dominant AD. With positron emission tomography imaging, it is now possible to study the disease many years before its clinical onset. Such studies can provide key knowledge regarding pathways for either the prevention of pathology or the postponement of its clinical expression. The former “resistance pathway” suggests that modifiable risk factors could affect amyloid and tau burden decades before the appearance of cognitive impairment. Alternatively, the resilience pathway suggests that modifiable risk factors may mitigate the symptomatic expression of AD pathology on cognition. These pathways are not mutually exclusive and may appear at different disease stages. Here, in a narrative review, we present neuroimaging evidence that supports both pathways in sporadic AD and autosomal-dominant AD. We then propose mechanisms for their protective effect. Among possible mechanisms, we examine neural and vascular mechanisms for the resistance pathway. We also describe brain maintenance and functional compensation as bases for the resilience pathway. Improved mechanistic understanding of both pathways may suggest new interventions.

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organization
publishing date
type
Contribution to journal
publication status
in press
subject
keywords
Alzheimer disease, Amyloid, Modifiable risk factors, Positron emission tomography, Prevention, Tau
in
Biological Psychiatry
publisher
Elsevier
external identifiers
  • pmid:37689129
  • scopus:85177032226
ISSN
0006-3223
DOI
10.1016/j.biopsych.2023.09.003
language
English
LU publication?
yes
id
03d4275c-cb02-42c1-8be6-6c69e05f7bd7
date added to LUP
2024-01-08 13:38:39
date last changed
2024-04-23 10:24:26
@article{03d4275c-cb02-42c1-8be6-6c69e05f7bd7,
  abstract     = {{<p>Epidemiological studies show that modifiable risk factors account for approximately 40% of the population variability in risk of developing dementia, including sporadic Alzheimer's disease (AD). Recent findings suggest that these factors may also modify disease trajectories of people with autosomal-dominant AD. With positron emission tomography imaging, it is now possible to study the disease many years before its clinical onset. Such studies can provide key knowledge regarding pathways for either the prevention of pathology or the postponement of its clinical expression. The former “resistance pathway” suggests that modifiable risk factors could affect amyloid and tau burden decades before the appearance of cognitive impairment. Alternatively, the resilience pathway suggests that modifiable risk factors may mitigate the symptomatic expression of AD pathology on cognition. These pathways are not mutually exclusive and may appear at different disease stages. Here, in a narrative review, we present neuroimaging evidence that supports both pathways in sporadic AD and autosomal-dominant AD. We then propose mechanisms for their protective effect. Among possible mechanisms, we examine neural and vascular mechanisms for the resistance pathway. We also describe brain maintenance and functional compensation as bases for the resilience pathway. Improved mechanistic understanding of both pathways may suggest new interventions.</p>}},
  author       = {{Ourry, Valentin and Binette, Alexa Pichet and St-Onge, Frédéric and Strikwerda-Brown, Cherie and Chagnot, Audrey and Poirier, Judes and Breitner, John and Arenaza-Urquijo, Eider M. and Rabin, Jennifer S. and Buckley, Rachel and Gonneaud, Julie and Marchant, Natalie L. and Villeneuve, Sylvia}},
  issn         = {{0006-3223}},
  keywords     = {{Alzheimer disease; Amyloid; Modifiable risk factors; Positron emission tomography; Prevention; Tau}},
  language     = {{eng}},
  publisher    = {{Elsevier}},
  series       = {{Biological Psychiatry}},
  title        = {{How Do Modifiable Risk Factors Affect Alzheimer's Disease Pathology or Mitigate Its Effect on Clinical Symptom Expression?}},
  url          = {{http://dx.doi.org/10.1016/j.biopsych.2023.09.003}},
  doi          = {{10.1016/j.biopsych.2023.09.003}},
  year         = {{2023}},
}