Cortisol, Amyloid-beta, and Reserve Predicts Alzheimer's Disease Progression for Cognitively Normal Older Adults

Udeh-Momoh, Chinedu T.; Su, Bowen; Evans, Stephanie; Zheng, Bang; Sindi, Shireen; Tzoulaki, Ioanna; Perneczkya, Robert und Middleton, Lefkos T. (2019): Cortisol, Amyloid-beta, and Reserve Predicts Alzheimer's Disease Progression for Cognitively Normal Older Adults. In: Journal of Alzheimers Disease, Bd. 70, Nr. 2: S. 551-560

Abstract

Elevated cortisol as a measure of hypothalamic-pituitary-adrenal-axis hyperactivity has emerged as a predictor of clinical progression of Alzheimer's disease (AD), in conjunction with amyloid-beta (A beta) abnormalities. Yet factors exist which have the propensity to delay AD symptomatic expression in the face of an AD-type biomarker-based pathological profile. This study sought to determine whether abnormal cerebrospinal fluid (CSF) A beta and elevated cortisol levels are associated with clinical transition to mild cognitive impairment (MCI) and AD in cognitively normal (CN) individuals, and if this association is modified by reserve proxies. Data from 91 CN individuals participating in the Alzheimer's Disease Neuroimaging Initiative (ADNI) with available morning CSF cortisol and A beta(42) were evaluated. Reserve was modelled as a latent composite score of standardized intracranial volume and lifetime experience proxies. Cox regressions were used to test associations between baseline CSF cortisol/A beta(42), reserve score and AD progression;adjusting for age, sex, apolipoprotein E genotype, and depressive symptoms. Individuals with elevated cortisol + abnormal A beta(42) levels at baseline showed highest risk of clinical progression. After a median of 84 months follow-up, significant cortisol/A beta/reserve interaction for clinical progression was noted (adjusted HR=0.15, p < 0.001), suggesting a moderating effect of reserve on the association between cortisol/A beta+ and clinical progression. Our findings indicate that cortisol hypersecretion accelerates clinical progression in CN individuals presenting with pathological A beta(42). High reserve reduces the associated AD progression risk in these high-risk individuals.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1387-2877
• Sprache: Englisch