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Abstract. This study was designed to investigate the therapeutic efficacy of estrogen in female patients with dementia of the Alzheimer type (DAT). Fifteen DAT patients with a mean age of (x ± SE) 71.9 ± 2.4 years were treated with 0.625 mg of conjugated equine estrogens orally twice a day for 6 weeks. Of the 15 DAT patients, 4 were diagnosed as mild, 7 as moderate and 4 as severe. The effects of estrogen on DAT patients were evaluated by psychometric assessments, behavior rating scales, regional cerebral blood flow (rCBF) measurement and quantitative EEG analysis. Psychometric assessments consisted of Mini-Mental State Examination (MMSE) and Hasegawa Dementia Scale (HDS). Dementia syndromes were evaluated by the CBS-Scale (GBSS) and Hamilton Depression Rating Scale (HDRS). During estrogen replacement therapy (ERT), the mean MMSE score (x ± SE) increased significantly from 11.6 ± 1.9 to 13.2 ± 2.0 at 3 weeks (P<0.01) and 13.8 ± 2.0 at 6 weeks (P<0.001). The mean HDS score increased significantly from 8.6 ± 2.1 to 11.5 ± 2.3 at 3 weeks (P<0.001) and 11.6 ± 2.6 at 6 weeks (P<0.01). Significant improvements in the mean scores of the GBSS and HDRS were also observed in the estrogentreated group, but not in the untreated control group with a mean age of 71.2 ± 2.5 years (n=15). The rCBF was measured by single photon emission computed tomography (SPELT). ERT increased the mean rCBF significantly in the lower frontal region (P<0.01) and primary motor area (P<0.02) of the right hemisphere. The mean absolute power delta band values in both left and right frontal EEG (Fp, and Fp2) (P<0.01) and theta1 band values in Fp2 (P<0.05) decreased significantly during ERT. It is inferred that ERT significantly improves cognitive functions, dementia symptoms, regional cerebral blood flow and EEG activity in female patients with DAT.

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Seven female patients with mild to moderate dementia of the Alzheimer type (DAT) were treated with long-term, low-dose estrogen replacement therapy (ERT) over a period of 5–45 months. Five of the 7 patients were cases who had responded well to short-term ERT with 1.25 mg/day of conjugated equine estrogens (CEE) for 6 weeks. The 7 patients from 56 to 77 years of age received 0.625 mg/day of CEE for 21 days, followed by a pause of 7 days. A28-day cycle of low-dose ERT was performed repeatedly. In 4 cases, these patients received 5 mg/day of medroxyprogesterone acetate (MPA) during the last 10–12 days of estrogen treatment. Therapeutic efficacy of estrogen was evaluated by psychometric assessments such as the Mini-Mental State Examination (MMSE) and the Hasegawa Dementia Scale (HDS) and a behavior rating scale of the Gottfries-Bråne-Steen geriatric rating scale (GBS). The MMSE and HDS evaluations were performed principally once in 2–4 weeks. In 4 out of the 7 patients, the MMSE and HDS scores were elevated above the pretreatment levels during ERT. The termination of ERT resulted in a decrease in both scores. Furthermore, the GBS scores and daily activities of the same 4 patients were improved during ERT. In these 4 patients cognitive functions were markedly improved throughout the treatment period, while the other 2 patients responded moderately well and another patient did not respond at all. These observations suggest that long-term, low-dose ERT improves cognitive functions, dementia symptoms and daily activities in women with mild to moderate DAT. However, the supplemental treatment with MPA seems to have an unfavorable effect on dementia symptoms and daily activities in the aged DAT patients.

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