Ourry, Valentin;
Binette, Alexa Pichet;
St-Onge, Frédéric;
Strikwerda-Brown, Cherie;
Chagnot, Audrey;
Poirier, Judes;
Breitner, John;
... Villeneuve, Sylvia; + view all
(2023)
How do modifiable risk factors affect Alzheimer's disease pathology or mitigate its effect on clinical symptom expression?
Biological Psychiatry
10.1016/j.biopsych.2023.09.003.
(In press).
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Abstract
Epidemiological studies show that modifiable risk factors account for about 40% of the population variability in risk of developing dementia, including sporadic Alzheimer's disease (sAD). Recent findings suggest that these factors might also modify disease trajectories of people with autosomal dominant Alzheimer's disease (ADAD). With positron emission tomography (PET) 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 might mitigate the symptomatic expression of AD pathology on cognition. These pathways are not mutually exclusive and might appear at different disease stages. Here, in a narrative review, we present neuroimaging evidence that supports both pathways in sAD and ADAD. 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.
| Type: | Article |
|---|---|
| Title: | How do modifiable risk factors affect Alzheimer's disease pathology or mitigate its effect on clinical symptom expression? |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.biopsych.2023.09.003 |
| Publisher version: | https://doi.org/10.1016/j.biopsych.2023.09.003 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Alzheimer’s disease, amyloid, modifiable risk factors, positron emission tomography, prevention, tau |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Division of Psychiatry UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Division of Psychiatry > Mental Health of Older People |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10178282 |
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