Therapeutic implications of hypothalamic-pituitaryadrenal-axis modulation in Alzheimer’s disease: A narrative review of pharmacological and lifestyle interventions

Tamlyn Watermeyer, Sarah Gregory, Catherine Robb, Chi Udeh-Momoh

Research output: Contribution to journalReview articlepeer-review

2 Citations (Scopus)

Abstract

With disease-modifying treatments for Alzheimer’s disease (AD) still elusive, the search for alternative intervention strategies has intensified. Growing evidence suggests that dysfunction in hypothalamic-pituitaryadrenal-axis (HPAA) activity may contribute to the development of AD pathology. The HPAA, may therefore offer a novel target for therapeutic action. This review summarises and critically evaluates animal and human studies investigating the effects of pharmacological and non-pharmacological intervention on HPAA modulation alongside cognitive performance. The interventions discussed include glucocorticoid receptor antagonists and 11β-hydroxysteroid dehydrogenase inhibitors as well as lifestyle treatments such as physical activity, diet, sleep and contemplative practices. Pharmacological HPAA modulators improve pathology and cognitive deficit in animal AD models, but human pharmacological trials are yet to provide definitive support for such benefits. Lifestyle interventions may offer promising strategies for HPAA modification and cognitive health, but several methodological caveats across these studies were identified. Directions for future research in AD studies are proposed.
Original languageEnglish
Article number100877
Number of pages18
JournalFrontiers in Neuroendocrinology
Volume60
Early online date9 Oct 2020
DOIs
Publication statusPublished - 1 Jan 2021

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