Article

The Framingham Brain Donation Program: Neuropathology Along the Cognitive Continuum

Department of Neurology, Boston University School of Medicine, 715 Albany Street, Boston, MA 02118, USA.
Current Alzheimer research (Impact Factor: 3.89). 04/2012; 9(6):673-86. DOI: 10.2174/156720512801322609
Source: PubMed

ABSTRACT

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.

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Available from: Sudha Seshadri, Jun 17, 2015
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    • "The need for brain tissue to support neuroscience research has led many institutions to call for brain donation programs, as the French Academy of Medicine did recently[34]. Variable consent rates have been reported in such programs, because of heterogeneous donor populations and modes of approach[15], from 10–20% in broad community-based cohorts[25,35], to very high donation rates in specific populations such as centenarians[36], or with specific recruitment protocols[37]. Moreover, although no study directly compared donation rates across neurodegenerative disorders , low autopsy rates do not seem to be confined to dementing conditions. "
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