Cerebrospinal fluid corticotropin-releasing hormone and ACTH, and peripherally circulating choline-containing phospholipid in senile dementia

Cerebrospinal fluid (CSF) levels of corticotropin-releasing hormone (CRH) and ACTH, plasma levels of ACTH and cortisol, and serum levels of phospholipid and its fractions were determined in samples taken simultaneously from patients with senile dementia of the Alzheimer type (SDAT), multi-infarct dementia (MID) or dementia following a cerebrovascular accident (CVD), and the borderline-to-normal control subjects. CRH levels in CSF were significantly reduced in patients with SDAT and CVD but not with MID compared to the borderline-to-normal controls. ACTH levels in CSF were significantly reduced in SDAT compared to MID. The levels of circulating lecithin (phosphatidyl-choline) were depressed in a similar fashion to the levels of CRH in CSF in the SDAT patients and the group of severe dementia. Dementia and its severity did not affect the morning plasma levels of ACTH and cortisol. CSF CRH was positively correlated with CSF ACTH, while CSF ACTH was negatively correlated with plasma cortisol. No significant correlations were found between serum lecithin and CSF CRH or ACTH. These findings suggest that: 1) abnormalities in the extrahypothalamic CRH system play a role in the pathophysiology of senile dementia, which may not be specific to SDAT; 2) the CRH system and the ACTH system correlate with each other within the brain; 3) CSF ACTH is subject to the feedback inhibition by circulating cortisol; and 4) in the SDAT patients and the severe dementia group CSF CRH and serum lecithin are reduced probably via independent mechanisms.