Early Markers Of Alzheimers Disease

工作总结：阿尔茨海默病（AD）是主要发生在较晚年龄的几种神经退行性疾病（痴呆）中最普遍的，偶尔在60岁之前，但更频繁地在70岁之后。本研究探讨了前瞻性的心理，神经和神经心理学的变化，参与者从巴尔的摩纵向研究老化（BLSA）。对60岁及以上的参与者进行神经学和神经心理学检查，重复在早期对这些受试者进行的许多测试。可能的阿尔茨海默病的诊断遵循NINCDS-ADRDA标准。 部分研究者在385名年龄在55岁及以上的非痴呆巴尔的摩老龄化纵向研究参与者中，使用连续的加州言语学习测试（CVLT）检查了与年龄相关的记忆变化和重复测试之间的关系。在这项研究中，我们调查了纵向变化和年龄，性别，教育和重复测试对新的学习和回忆的影响，通过分析措施的学习和干扰，短期和长期延迟的自由和线索回忆，并在单独的混合效应回归识别命中。我们发现年龄（p < 0.001）和性别（p < 0.05）对学习和干扰的横截面影响，与基线表现无关。年轻人的表现优于老年人，女性的表现优于男性。纵向年龄变化记录在总的学习和长延迟自由和线索回忆，无论基线得分（p <= 0.05）。此外，控制基线评分提高了检测试验5中纵向年龄变化、短时延迟线索回忆和再认命中的灵敏度（p < 0.05）。重复给药的影响随着总学习和短期和长期延迟回忆的基线年龄的增加而变化，因此较年轻的基线年龄与随时间的改善相关，而较年长的基线年龄与随时间的下降相关。这些结果表明，有纵向下降CVLT性能在正常老化，这些变化的影响，基线年龄。此外，未能解释重复测试与衰老的影响可能会降低检测病理性下降的敏感性。 科调查员还检查了是否阿尔茨海默病？老年痴呆症反映了一个慢性过程，在痴呆症临床表现之前多年就开始了。在这项研究中，我们检查了是否病前本顿视觉保持测试（BVRT）和韦氏成人智力量表词汇（WAIS-VXI）的测试成绩，以确定是否长期赤字在这些测试可以预测AD的发展几十年后在巴尔的摩老龄化纵向研究（BLSA）。1，425名年龄超过60岁的BLSA参与者被纳入分析。考克斯比例风险模型用于估计AD诊断前20年内不同时间段与BVRT和WAIS-Risk评分相关的AD发生相对风险。在AD诊断前1 - 3年、3 - 5年、5 - 10年和10 - 15年，6次或以上BVRT错误与少于6次错误的相对风险分别为5.69、2.11、1.76和1.83（p < 0.05）。诊断前15年或更长时间的相对危险度无显著性差异（p > 0.10）。在任何时间段内，WAIS-TBI评分与AD风险均无显著相关性。这些结果表明，BVRT的错误数量越多，15年后AD的风险越高。较差的视觉记忆表现可能代表AD在诊断前数年的早期表达。这一结果表明，需要继续修改对AD自然史的看法，并在确诊前增加预防性治疗的机会。 我们研究了与年龄相关的内源性血清T和游离T浓度下降与神经心理学表现下降之间的关系。参与者是来自巴尔的摩老龄化纵向研究的志愿者，在基线T评估时年龄为50-91岁。对407名男性进行了平均10年的随访，评估了多个认知领域，同时测定了血清总T、SHBG和游离T指数（FTI）。我们进行了语言和视觉记忆、精神状态、视觉扫描和注意力、语言知识/语言、视觉空间能力和抑郁症的神经心理学测试。较高的FTI与视觉和语言记忆、视觉空间功能和视觉扫描的较好分数以及视觉记忆纵向下降率的降低相关。被归类为性腺功能减退的男性在记忆和视觉空间表现方面的得分明显较低，视觉记忆下降的速度更快。总T或FTI和言语知识，精神状态或抑郁症状的措施之间没有关系。这些结果表明，在老年男性中，循环游离T浓度和特定领域的认知能力之间可能存在有益的关系。

Summary of work: Alzheimer's 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 Alzheimer's disease follow the NINCDS-ADRDA criteria. Section investigators examined the relationship between age-related memory change and repeat testing using serial administrations of the California Verbal Learning Test (CVLT) in 385 nondemented Baltimore Longitudinal Study of Aging participants aged 55 and older with two or more memory assessments. In this study, we investigated longitudinal change and the effects of age, sex, education, and repeat testing on new learning and recall by analyzing measures of learning and interference, short- and long-delay free and cued recall, and recognition hits in separate mixed-effects regressions. We found cross-sectional effects of age (p < 0.001) and sex (p < 0.05) on learning and interference, regardless of baseline performance. Younger adults outperformed older adults, and women outperformed men. Longitudinal age changes were documented across total learning and long-delay free and cued recall regardless of baseline scores (p <= 0.05). In addition, controlling for baseline scores enhanced the sensitivity for detection of longitudinal age changes on Trial 5, short-delay cued recall and recognition hits (p < 0.05). The influence of repeated administrations changed with advancing baseline age for total learning and short- and long-delay recall such that younger baseline age was associated with improvement over time whereas older baseline age was associated with decline over time. These results suggest that there are longitudinal declines in CVLT performance in normal aging and these changes are influenced by baseline age. Furthermore, failure to account for the influence of repeat testing with aging may decrease sensitivity to detect pathologic decline. Section investigator also examined whether Alzheimer?s disease reflects a chronic process that begins many years before the clinical expression of dementia. In this study, we examined whether premorbid Benton Visual Retention Test (BVRT) and Wechsler Adult Intelligence Scale-vocabulary (WAIS-voc) test scores in order to determine whether long-term deficits in these tests can predict the development of AD decades later in the Baltimore Longitudinal Study of Aging (BLSA). 1,425 BLSA participants who were older than 60 years were included in the analyses. Cox proportional hazards models were used to estimate the relative risk of developing AD associated with BVRT and WAIS-voc scores at different time periods up to 20 years before the diagnosis of AD. The relative risks for 6 or more BVRT errors vs less than 6 errors at 1 to 3, 3 to 5, 5 to 10, and 10 to 15 years before the diagnosis of AD were 5.69, 2.11, 1.76, and 1.83 (p < 0.05). The relative risk for 15 or more years before diagnosis was not significant (p > 0.10). WAIS-voc scores were not significantly associated with the risk of AD in any time period. These results suggest that a greater number of errors on the BVRT is associated with an increased risk of AD up to 15 years later. Poor visual memory performance may represent an early expression of AD years before diagnosis. This result suggests the need to continue to revise views on the natural history of AD and the possibility of an increased window of opportunity for preventive treatment before definitive diagnosis. We examined the relationships between age-associated decreases in endogenous serum T and free T concentrations and declines in neuropsychological performance. Participants were volunteers from the Baltimore Longitudinal Study of Aging, aged 50-91 yr at baseline T assessment. Four hundred seven men were followed for an average of 10 yr, with assessments of multiple cognitive domains and contemporaneous determination of serum total T, SHBG, and a free T index (FTI). We administered neuropsychological tests of verbal and visual memory, mental status, visuomotor scanning and attention, verbal knowledge/language, visuospatial ability, and depressive symptomatology. Higher FTI was associated with better scores on visual and verbal memory, visuospatial functioning, and visuomotor scanning and a reduced rate of longitudinal decline in visual memory. Men classified as hypogonadal had significantly lower scores on measures of memory and visuospatial performance and a faster rate of decline in visual memory. No relations between total T or the FTI and measures of verbal knowledge, mental status, or depressive symptoms were observed. These results suggest a possible beneficial relationship between circulating free T concentrations and specific domains of cognitive performance in older men.