EARLY MARKERS OF ALZHEIMER DISEASE

工作摘要：阿尔茨海默病(AD)是几种神经退行性疾病(痴呆症)中最常见的，主要发生在晚年，偶尔在60岁之前，但更常见于70岁以后。这项研究调查了巴尔的摩老龄化纵向研究(BLSA)参与者的预期心理、神经和神经心理变化。对60岁及以上的参与者进行神经学和神经心理学检查，重复许多在年龄较小时对这些受试者进行的测试。疑似阿尔茨海默病的诊断遵循NINCDS-ADRDA标准。雌激素替代疗法(ERT)因其对老年妇女身体健康的有益影响，越来越多地被推荐给绝经后妇女。最近的研究表明，ERT可能对认知功能具有保护作用，并可能降低阿尔茨海默病的风险。我们从巴尔的摩老龄化纵向研究中测试了ERT是否对非痴呆女性的记忆有保护作用。研究小组包括103名口服或透皮ERT的活跃使用者和81名从未使用ERT的人，他们在评估后5年内没有痴呆。他们在教育程度、健康状况、抑郁症状、年收入和一般语言能力等方面进行了匹配。数据是横截面的。在加州语言学习测试(P&lt；0.05)的几项测试中，ERT用户的语言学习和记忆能力明显好于从不使用ERT的用户，但在图形记忆、心理旋转、注意力或工作记忆测试中表现不佳。ERT的使用与增强的语言信息编码和提取有关，并且对记忆过程中的干扰不那么敏感。记忆性能不随使用时间的延长而变化，也不随同时使用孕酮而变化。数据表明，ERT对记忆有显著的选择性影响。这些发现表明，有必要进行纵向研究，以确定在非痴呆女性中使用ERT是否可以防止与年龄相关的记忆下降。高浓度的脱氢表雄酮(DHEA)可以防止或逆转正常的与年龄相关的记忆和认知功能下降。在美国，DHEA作为一种非处方药被广泛使用，老年人会自行开出处方，以阻止与年龄相关的认知和身体变化。在这项研究中，我们调查了内源性DHEA浓度下降和认知能力下降之间的关系。受试者是巴尔的摩老龄化纵向研究的参与者，这是一个居住在社区的志愿者样本，年龄在22岁到91岁之间，其中883名男性接受了长达31年(平均为11.55年)的随访，每两年重新评估多个认知领域和同期血浆DHEA。言语和视觉记忆的认知测试，精神状态、音素和语义单词流畅性的两项测试，以及视觉运动扫描和注意力的测量。用标准放射免疫法测定血浆DHEA浓度。脱氢表雄酮的下降率和个体内的平均脱氢表雄酮浓度都与认知状态或认知衰退无关。最高和最低DHEA四分位数之间的极端组比较显示没有认知差异，尽管在平均12年的时间里，这些组在内源性DHEA浓度方面的差异超过4倍。我们的纵向结果与之前的横断面研究一致，这些研究表明，脱氢表雄酮的内源性下降与认知状态和健康老龄化中的认知下降无关。-认知能力、认知障碍、阿尔茨海默病-人类受试者和人类受试者：仅采访、问卷或调查

Summary of work: Alzheimers disease (AD) is the most widespread among several neurological degenerative diseases (dementias) that occur principally at later ages, occasionally before 60, but more frequently after age 70. This study examines prospective psychological, neurological, and neuropsychological changes in participants from the Baltimore Longitudinal Study of Aging (BLSA). Neurological and neuropsychological examinations are administered to participants aged 60 and older, repeating many of the tests that were administered to these subjects at earlier ages. Diagnoses of probable Alzheimers disease follow the NINCDS-ADRDA criteria. Estrogen replacement therapy (ERT) is increasingly recommended for post-menopausal women due to its beneficial effects on physical health in older women. Recent studies have suggested that ERT may have a protective effect on cognitive function and may reduce the risk for Alzheimers disease. We tested whether ERT had a protective effect on memory in nondemented women from the Baltimore Longitudinal Study of Aging. Study groups included 103 active users of oral or transdermal ERT and 81 never-users who were free of dementia up to 5 years after assessment. Groups were matched on education, health status, depressive symptoms, annual income, and general verbal ability. Data were cross-sectional. ERT users showed significantly better verbal learning and memory than never-users on several measures of the California Verbal Learning Test, p < .05, but not on tests of figural memory, mental rotations, attention or working memory. ERT use was associated with enhanced encoding and retrieval of verbal information, and less sensitivity to interference during memory performance. Memory performance did not vary with duration of use nor with concurrent progesterone use. Data suggest a significant and selective effect of ERT on memory. These findings indicate the need for longitudinal studies to determine whether ERT use protects against age- related memory decline in nondemented women.High concentrations of dehydroepiandrosterone (DHEA) may prevent or reverse normal age-related declines in memory and cognitive function. DHEA is widely available in the United States as an over-the-counter supplement that elderly individuals are self-prescribing to impede age-related cognitive, as well as physical change. In this study, we investigated the relationship between declines in endogenous DHEA concentrations and declines in cognitive performance. Subjects were participants in the Baltimore Longitudinal Study of Aging, a community-dwelling volunteer sample aged 22 to 91 years at initial visit in which 883 men were followed up to 31 years (mean = 11.55 years) with biennial reassessments of multiple cognitive domains and contemporaneous plasma DHEA. Cognitive tests of verbal and visual memory, 2 tests of mental status, phonemic and semantic word fluency, and measures of visuomotor scanning and attention. Plasma DHEA concentrations were determined by standard radioimmunoassay. Neither the rate of decline in DHEA nor the within-individual mean DHEA concentrations were related to cognitive status or cognitive decline. An extreme-groups comparison between the highest and lowest DHEA quartiles revealed no cognitive differences, despite the fact that these groups differed in endogenous DHEA concentration by more than a factor of 4 for an average duration of 12 years. Our longitudinal results are consistent with previous cross- sectional studies suggesting that endogenous decline in DHEA is independent of cognitive status and cognitive decline in healthy aging. - cognitive ability, cognitive impairment, Alzheimer's disease - Human Subjects & Human Subjects: Interview, Questionaires, or Surveys Only