TY - JOUR
T1 - Therapeutic implications of hypothalamic-pituitaryadrenal-axis modulation in Alzheimer’s disease
T2 - A narrative review of pharmacological and lifestyle interventions
AU - Watermeyer, Tamlyn
AU - Gregory, Sarah
AU - Robb, Catherine
AU - Udeh-Momoh, Chi
PY - 2021/1/1
Y1 - 2021/1/1
N2 - 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.
AB - 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.
U2 - 10.1016/j.yfrne.2020.100877
DO - 10.1016/j.yfrne.2020.100877
M3 - Review article
SN - 0091-3022
VL - 60
JO - Frontiers in Neuroendocrinology
JF - Frontiers in Neuroendocrinology
M1 - 100877
ER -
