Department of Neurology, Boston University School of Medicine, 715 Albany Street, Boston, MA 02118, USA.
Curr Alzheimer Res. 2012 Jul;9(6):673-86. doi: 10.2174/156720512801322609.
The Framingham Heart Study has enrolled 3 generations of participants, the original cohort (gen 1) enrolled in 1948, the offspring cohort (gen 2) enrolled in 1971 and the third generation enrolled in 2002. Participants have been undergoing prospective surveillance for incident stroke and dementia and embedded within this cohort is the voluntary Framingham Brain Donation Program that was begun in 1997. Participants who register to become brain donors have had one or more brain MR and cognitive test batteries administered. In addition, they undergo neurological evaluation as indicated, record review and post-mortem next-of-kin interview to determine the presence, type and extent of antemortem, clinical neurological diagnoses and to assign a retrospective clinical dementia rating (CDR) Scale score. Between 1997 and 2009 there were 1806 deaths, 186 of which were among registered brain donors and of these 139 brains could be examined. 58% were deemed cognitively normal at death. We present results for 3 projects; the first was to examine the sensitivity and specificity of our clinical diagnosis against the gold standard of pathological AD in 59 persons who underwent detailed cognitive assessment in the two years prior to death; we observed a 77.3% sensitivity (2 persons with AD were diagnosed clinically as Lewy body dementia) and a 91.9% specificity. The second examined the correlation of regional Alzheimer-type pathology to cognitive status at death among 34 persons who were over the age of 75 and without any significant vascular or alternative neurodegenerative pathology and found that neurofibrillary tangle counts distinguished between persons who were controls, had mild cognitive impairment, mild or moderate dementia; tangles in dorsolateral frontal cortex best distinguished MCI and controls. The third project examined the extent and severity of vascular pathology, again in a larger sample of varying cognitive abilities and in a subsample of persons with either amnestic or nonamnestic MCI. We observed that an aggregate ischemic injury score was significantly higher in persons with a CDR score of 0.5 than in normal controls.
弗雷明汉心脏研究已经招募了 3 代参与者，最初的队列（第一代）于 1948 年招募，后代队列（第二代）于 1971 年招募，第三代于 2002 年招募。参与者一直在接受前瞻性监测，以发现中风和痴呆的病例，并在该队列中嵌入了自愿的弗雷明汉大脑捐赠计划，该计划始于 1997 年。登记成为大脑捐赠者的参与者已经接受了一次或多次大脑磁共振成像（MRI）和认知测试。此外，根据需要进行神经学评估、记录审查和死后近亲访谈，以确定生前、临床神经学诊断的存在、类型和程度，并分配回顾性临床痴呆评定量表（CDR）评分。1997 年至 2009 年间有 1806 人死亡，其中 186 人是登记的大脑捐赠者，其中 139 人的大脑可以进行检查。58%的人在死亡时被认为认知正常。我们介绍了 3 个项目的结果；第一个是检查我们的临床诊断在 59 名在死亡前两年接受详细认知评估的人中对病理 AD 的金标准的敏感性和特异性；我们观察到 77.3%的敏感性（2 名 AD 患者被临床诊断为路易体痴呆）和 91.9%的特异性。第二个研究了 34 名年龄在 75 岁以上且没有任何明显血管或其他神经退行性病变的人的认知状态与大脑中阿尔茨海默病样病理的相关性，发现神经原纤维缠结计数可以区分控制组、轻度认知障碍、轻度或中度痴呆患者；背外侧额叶皮质中的缠结可以最好地区分 MCI 和对照组。第三个项目研究了血管病变的程度和严重程度，同样是在具有不同认知能力的更大样本中，以及在有遗忘型或非遗忘型 MCI 的亚样本中进行研究。我们观察到，在 CDR 评分为 0.5 的人中，总的缺血性损伤评分明显高于正常对照组。
