Age, Alzheimer's disease and dementia in the Baltimore Longitudinal Study of Ageing
Age, Alzheimer's disease and dementia in the Baltimore Longitudinal Study of Ageing
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DOI：
10.1093/brain/awq141
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发表时间：
2010-08-01
期刊：
影响因子：
14.5
通讯作者：
O'Brien, Richard J.
中科院分区：
文献类型：
--
作者：
Dolan, David;Troncoso, Juan;O'Brien, Richard J.
近期研究表明，高龄老年人（90岁及以上）的痴呆与阿尔茨海默病病理仅有适度关联。这增加了一种可能性，即其他尚未知晓的疾病过程可能是这一快速增长的人口群体患痴呆的潜在原因，而且旨在对抗阿尔茨海默病的措施可能不适用于治疗高龄受试者的痴呆。为了更深入地研究这一问题，我们在巴尔的摩衰老纵向研究的209名参与者的连续尸检中，检验了新皮质阿尔茨海默型脑部病理与痴呆之间的关系，该研究是一项关于衰老对认知影响的前瞻性纵向队列研究。该队列中近一半人在死亡时年龄超过90岁。我们发现，新皮质阿尔茨海默病病理的若干指标，包括建立阿尔茨海默病登记处联盟的神经炎性斑块评分和布拉克神经原纤维缠结评分，仍然是痴呆的重要预测因子，且与年龄无关。在年龄超过90岁的参与者中，颅内动脉粥样硬化在阿尔茨海默病病理评分较低的受试者中成为痴呆的一个重要预测因子，但并没有降低阿尔茨海默病病理高评分对痴呆几率的重要性或人群归因风险。有证据表明，在最年长的受试者中，神经原纤维病理导致痴呆的阈值评分有所提高，但这被该年龄组神经原纤维病理的总体增加所抵消。我们得出结论，新皮质阿尔茨海默病病理仍然与痴呆显著相关，且与年龄无关。在高龄老年人中，动脉粥样硬化在阿尔茨海默病病理评分较低的受试者中也成为痴呆的一个病因。我们没有发现大量老年人患痴呆却无明显病因的证据。
Recent studies suggest that dementia in the most elderly (90 years of age and above) is only modestly related to Alzheimer's disease pathology. This raises the possibility that other, as yet unknown, disease processes may underlie dementia in this rapidly growing demographic group, and that efforts designed to combat Alzheimer's disease may not be appropriate for treating dementia in very elderly subjects. To study this question more closely, we examined the relationship between neocortical Alzheimer-type brain pathology and dementia in consecutive autopsies from 209 participants in the Baltimore Longitudinal Study of Ageing, a prospective longitudinal cohort study of the effect of ageing on cognition. Almost half of the cohort was older than 90 years of age at death. We found that several measures of neocortical Alzheimer's pathology, including the Consortium to Establish a Registry of Alzheimer's Disease neuritic plaque score and the Braak neurofibrillary tangle score, remained significant predictors of dementia, independent of age. In participants older than 90 years of age, intracranial atherosclerosis emerged as an important predictor of dementia in subjects with low Alzheimer's pathology scores, but did not mitigate the importance or population attributable risk of high Alzheimer's pathology scores on the odds of dementia. There was evidence that the threshold score for neurofibrillary pathology to cause dementia increased in the oldest subjects, but this was offset by an overall increase in neurofibrillary pathology in this age group. We conclude that neocortical Alzheimer's disease pathology remains significantly correlated with dementia, independent of age. In the most elderly, atherosclerosis also emerged as a cause of dementia in subjects with low Alzheimer's pathology scores. We found no evidence for a significant number of elderly subjects having dementia without an apparent cause.