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

Binette, Alexa Pichet (author): Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,LU profilområde: Proaktivt åldrande,Lunds universitets profilområden,Clinical Memory Research,Lund University Research Groups,LU Profile Area: Proactive Ageing,Lund University Profile areas,McGill University,Douglas Mental Health University Institute

Strikwerda-Brown, Cherie (author): McGill University,University of Western Australia, Perth

Buckley, Rachel (author): Melbourne School of Psychological Sciences,Massachusetts General Hospital,Harvard Medical School,Brigham and Women's Hospital / Harvard Medical School

Gonneaud, Julie (author)

Villeneuve, Sylvia (author): McConnell Brain Imaging Centre,McGill University

(creator_code:org_t)

Related links:: http://dx.doi.org/10...; show more...; https://lup.lub.lu.s...; https://doi.org/10.1...; show less...

Abstract Subject headings

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.

By the author/editor: Ourry, Valentin; Binette, Alexa P ...; St-Onge, Frédéri ...; Strikwerda-Brown ...; Chagnot, Audrey; Poirier, Judes; show more...; Breitner, John; Arenaza-Urquijo, ...; Rabin, Jennifer ...; Buckley, Rachel; Gonneaud, Julie; Marchant, Natali ...; Villeneuve, Sylv ...; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Neurology

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