Several lines of evidence have suggested altered functions of the brain-derived neurotrophic factor (BDNF) in the pathogenesis of neurodegenerative diseases including Alzheimer's disease (AD).In the search for polymorphisms in the 5Ј-flanking and 5Ј-noncoding regions of the BDNF gene, we found a novel nucleotide substitution (C270T) in the noncoding region. We performed an association study between this polymorphism and AD in a Japanese sample of 170 patients with sporadic AD (51 early-onset and 119 late-onset) and 498 controls. The frequency of individuals who carried the mutated type (T270) was significantly more common in patients with late-onset AD than in controls (P = 0.00004, odds ratio: 3.8, 95% CI 1.9-7.4). However, there was no significant difference in the genotype distribution between the patients with early-onset AD and the controls, although this might be due to the small sample size of the early-onset group. Our results suggest that the C270T polymorphism of the BDNF gene or other unknown polymorphisms, which are in linkage disequilibrium, give susceptibility to late-onset AD. We obtained no evidence for the possible interactions between the BDNF and apolipoprotein E (APOE) genes, suggesting that the possible effect of the BDNF gene on the development of late-onset AD might be independent of the APOE genotype. Molecular Psychiatry (2001) 6, 83-86.Alzheimer's disease (AD) is a neurodegenerative disease characterized by loss and atrophy of basal forebrain cholinergic neurons and the limbic structures.

We studied an 84-year-old man with a 20-year history of nocturnal violent behavior during sleep, but no other clinically evident neuropsychiatric disorders. Polysomnographic investigations confirmed that he suffered from REM sleep behavior disorder (RBD). Histopathologic examination revealed he had Lewy body disease with a marked decrease of pigmented neurons in the locus ceruleus and substantia nigra. These histologic findings represent the first documented evidence of a loss of brainstem monoaminergic neurons in clinically idiopathic RBD and suggest that Lewy body disease might provide an explanation for idiopathic RBD in the aged.

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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