Neuroendocrine Theories

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Hypercortisolemia associated with late-life depression has been found to be associated with neuronal degeneration in the rat as well as human hippocampus (Sapolsky, 2000; Sheline, Wang, Gado, Csernansky, & Vannier, 1996). Thus, a neuroendocrine hypothesis for depression as a risk factor for dementia holds that late-life depression-induced cortisolemia could cause hippocampal degeneration and eventual cognitive decline. Lupien et al. (1994) found that aged subjects showing significantly increased cortisol levels with age and with high basal cortisol levels had impaired cognitive performance compared to aged controls without those abnormalities. Katona and Aldridge (1985) found failure of suppression on the Dexam-ethasone Suppression Test (DST) in 10 of 20 patients with dementia; non-suppressors had significantly higher depression scores on the Depressive Signs Scale (DSS) than suppressors. Following antidepressant treatment, three of eight nonsuppressors reverted to normal suppression, but this was not associated with clinical improvement.

Orcadian rhythm disturbance has been hypothesized to contribute to mental decline and depressive mood in AD (Moe, Vitello, Larsen, Larsen, & Prinz, 1995). Liu et al. (2000) investigated the expression of neuropep-tide vasopressin (AVP) mRNA in the human suprachiasmatic nucleus of AD patients with and without depression as well as age-matched controls. No significant differences were found in amount of AVP mRNA between AD patients with and without depression.

A link between estrogen replacement therapy and upregulation of serotonin and acetylcholine has been noted in healthy women (Toran-Allerand et al., 1992). One clinical trial found that female AD patients using estrogen replacement had better cognitive response to the cholinesterase inhibitor tacrine (Schneider & Farlow, 1997). The relationship between mood and estradiol levels has been studied in women with AD (Carlson, Sherwin, & Chertkow, 2000). Compared to healthy elderly controls, depression ratings were highest in AD women who were nonestrogen users. The authors suggested that women with AD who are not taking estrogen replacement may be especially vulnerable to depression.

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