Estrogen and cerebral blood flow: A mechanism to explain the impact of estrogen on the incidence and treatment of Alzheimer's disease

Objective-Women are three times as likely to develop late-onset Alzheimer's Disease (AD) as are age-matched men. In the perimenopausal period, women t ypically have profound hypoestrogenism associated with vasomotor episodes. The pattern of AD development in women resembles the hormonal changes that occur in the perimenopausal period; the risk of AD is lower in menopausal w omen taking estrogen replacement therapy (ERT), and ERT is associated with clinical improvement in AD patients. Further, ERT has been shown to augment the therapeutic benefits of medications designed to treat AD. To understan d better the relationship between ERT, hot flushes and AD, a pilot study wa s conducted at UCLA-Harbor Medical Center. Patients and Methods-Twelve heal thy menopausal women experiencing daily hot flushes and not on ERT were rec ruited to participate in a clinical study. Each patient underwent regional cerebral blood flow (CBF) measurement using single-photon emission computed tomography (SPECT) at baseline and during a hot flush episode. Patients we re then randomized to receive either 0.625 mg or 1.25 mg conjugated equine estrogens (CEE) daily. During the sixth week of ERT, each patient had a rep eat SPECT study. Baseline SPECT data were compared with ERT data. Results-B aseline examinations demonstrated CBF patterns commonly seen in patients wi th Alzheimer's disease. There was a global improvement in CBF associated wi th ERT, an average gain of 22% over baseline. Improvements were most dramat ic in the temporal and parietal regions of the brain. The cortical CBF demo nstrated a mean increase of 9.2 mL/100 g/min (P < .01). Conclusions-CBF is diminished in hypoestrogenic women, with regional patterns resembling those of patients with mild to moderate AD. Cerebral circulation tends to be fur ther compromised during hot flush episodes. This mechanism could be the ini tiating event in the metabolic process that results in dementia of the Alzh eimer's type, and thus serve as the link between hypoestrogenism and neurod egenerative diseases. In this study, ERT reversed these detrimental: blood flow changes back to a normal pattern after only 6 weeks of CEE therapy. Wi th improved blood flow, the brain is protected from the metabolic injury as sociated with hypoxia. The study is currently being repeated with a larger population.