| Background:An increased Alzheimer's disease (AD) risk has been reported in estrogen-deficient postmenopausal women and estrogen replacement therapy may improve cognitive profile and prevent cognitive decline. Levels of testosterone (T) decrease gradually with aging in men after 50yr. In several small sample randomized clinical trials, T replacement therapy has been shown to enhance visiospatial cognition. These observations raise the question of whether the loss of androgens with the aging may be associated with cognitive decline in elderly men.Objectives:To investigate whether levels of endogenous T and estradiol (E2) in older men are associated with dementia and cognition. (1) Whether the levels of total T (TT) and E2 decrease in male patients with dementia and mild cognitive impairment (MCI). Whether there is any relationship between the hormone deficiency and the etiological causes and severity of dementia. (2) Whether the deficiency of T and E2 increase the risk of cognitive impairment. (3) The effects of orchectomy and endogenous T and E2 on cognitive function in older men with and without MCI, AD, vascular dementia (VaD), and if there are any differences among them. (4) The gonadotropin levels in men with AD and VaD.Design:A cross-section study.Methods:We included 15 men with MCI (average 83.2±5.0yr), 35 men with AD (.84.6 ± 4.1yr), 3 men with MCI of the vascular type (82.7 ±3.2yr), 18 men with VaD(83.9 ±4.0yr) and 28 elderly controls (79.1±5.3yr) . We also included 30 prostate cancer patients with orchectomy, in which 6 men with MCI (2 diagnosed before operation), 7 men with AD (3 diagnosed before operation), 2 men with MCI of the vascular type, 3 men with VaD (2 diagnosed before operation) and 12 men with diagnosed before operation normal cognitive functions. The average age at examination was 84.8±5.4yr, and 80.1±5.7yr at operation, and the duration of follow-up averaged 4.7±2.2yr.T, E2, follicle-stimulating hormone, luteinizing hormone, prolactin were measured. Standard neuropsychological examination were performed in all participates except those in serious degrees, including mini-mental state examination, word list learning, recall and recognize, clock drawing test, constructive examination, figure copy and recall, picture recall, verbal fluency (animal), Tail Making A, and block design, digital span, similarity, comprehension, digital-symbol from WAIS-RC.Results:(1): Levels of TT and E2 were significantly lower in men with AD (11.5±6.8nmol/L, 81.2±74.7pmol/L, respectively) compared with controls (TT: 17.3±5.7nmol/L; E2: 133.2±100.0pmol/L, P<0.05). T deficiency was present in 57.1% of AD patients, which was significantly higher than those of controls (21.4%, p<0.05). Percentage of E2 deficiency was also higher in men with AD (74.3%) than controls (42.9%). There were not a significant decline of serum TT and E2 in patients with VaD compared with controls. Percentage of TT (44.4%) or E2 (66.7%) deficiency of VaD did not increased significantly too when compared to controls. In men with MCI, no significant changes of TT and E2 levels were found.(2): Levels of TT and E2 in men with AD decreased with the severity of dementia(Spearman's ps = -0.4709, P= 0.0000; Spearman's ps =-0.2635, P=0.0197). The trend of TT (Spearman's ps =-0.3482, P=0.0142) rather than E2 was also found in men with VaD.(3): Deficiency of T and E2 did not increase the risk for AD when comparing mild to moderate AD to normal controls. But the risk for aggravation was increased (OR=6.2, 95%CI = 1.2~32.2) when comparing moderate to serious AD to mild AD.(4): Serum LH (Spearman's ps =0.4016, P=0.0342) and FSH (Spearman's ps =0.4201, P=0.026) increased with age. Level of E2 had a negative relation with FSH in AD group [F(1,33) = 5.39, P = 0.0266, P = -0.359887, 95%CI= -0.6753477--0.0444263]. But the level of LH and FSH did not differ significantly among AD, VaD and controls.(5): All the other cognitive examinations were in normal range except for forward digital span score , which was significant...
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