Increased Levels of Adrenocortical and Gonadal Hormones in Mild to Moderate Alzheimer’s Disease

Abstract

Hormonal changes during normal aging include decreasing levels of gonadal hormones and adrenal androgens. These hormones influence multiple nervous functions, including cognition and mood. Related to this, abnormalities at several levels of the hypothalamic-pituitary-adrenal axis (HPA) have been reported in patients with Alzheimer’s disease (AD). We studied steroid hormones in 33 patients with mild to moderate AD (12 men; 21 women, 76.4 ± 7.8 years) and 22 healthy elderly controls (10 men; 12 women, 75.4 ± 7.5 years old, respectively). Basal levels of serum cortisol, dehydroepiandrosterone (DHEA) and androstenedione were significantly increased in AD patients. Women with AD had significantly higher levels of DHEA and androstenedione. Serum estradiol levels were non-significantly increased in women with AD. After adjustment for age and BMI women with AD had significantly increased levels of androstenedione and DHEA. Increased gonadal hormone levels in mild to moderate AD may reflect an increased secretion, and/or alterations in metabolism of these hormones. This may influence the symptomatology and progression of the disease.

Androgen cell signaling pathways involved in neuroprotective actions

“…In subsequent studies by this group, both total (Hogervorst et al, 2004;Hogervorst et al, 2003;Lehmann et al, 2004) and free (Hogervorst et al, 2002) testosterone levels were found to be significantly lower in men without AD irrespective of potentially confounding such indices as age, education, body mass index, smoking, alcohol use, diabetes, and hormone therapy. Similar findings of low testosterone in men with AD have been reported in several (Almeida et al, 2004;Moffat et al, 2004;Paoletti et al, 2004;Rasmuson et al, 2002;Watanabe et al, 2004) but not all (Pennanen et al, 2004) studies. Interestingly, low testosterone has also been linked to several other neurodegenerative diseases, including Parkinson's disease (Okun et al, 2004), vascular dementia (Watanabe et al, 2004), amyotropic lateral sclerosis (Militello et al, 2002), and Huntington's disease (Markianos et al, 2005).…”

Steroid and nonsteroidal anti-inflammatory drugs, cognitive decline, and dementia

“…Several studies in the elderly have demonstrated a potentially reversible link between elevated endogenous cortisol levels and decline in memory and frontal-executive abilities (Greendale et al, 2000;O'Hara et al, 2007;Seeman et al, 1997;Li et al, 2006;Beluche et al, 2010;Egeland et al, 2005) and dementia (Umegaki et al, 2000;Rasmuson et al, 2002;Csernansky et al, 2006). Associations between short-term CS administration and cognitive impairment have been reported in small experimental and clinical studies in adults (Wolkowitz et al, 2009;Newcomer et al, 1999;Kirschbaum et al, 1996;Lupien et al, 2007;Young et al, 1999;de Quervain et al, 2003;Keenan et al, 1996).…”

Plasma Cortisol and Progression of Dementia in Subjects With Alzheimer-Type Dementia

“…Increases in plasma cortisol levels have been reported in individuals with probable AD (19,20,21,22,23), but have been generally interpreted as evidence that the disease process of AD (i.e., AD-induced hippocampal degeneration) leads to dysinhibition of the HPA axis. In line with this hypothesis, correlations have been reported between increases in HPA axis activity and dementia severity (24) or hippocampal volume loss (25,26) in individuals with probable AD.…”