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Cited by 65Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsNeurological Disease Mechanisms and Treatments

The Framingham Brain Donation Program: Neuropathology Along the Cognitive Continuum

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Au, Rhoda, Seshadri, Sudha, Knox, Kristen, Beiser, Alexa, J. Himali, Jayandra, J. Cabral, Howard, Auerbach, Sanford, C. Green, Robert +2 more·2012·Current Alzheimer Research
DOI 10.2174/156720512801322609PMC PMC3622706
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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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  • AD neuropathologic change is documented in approximately 80% of cases with a traditional clinical diagnosis of "AD dementia".

    “AD neuropathologic change is documented in approximately 80% of cases with a traditional clinical diagnosis of “AD dementia” (see Fig. 5 for an example of clinical misdiagnosis of “AD dementia”) [50–52,162,185,209–211].”

    From NIA‐AA Research Framework: Toward a biological definition of Alzheimer's disease (2018) · cites this paper as [211]

    Project 1, Methods and Results (page unavailable), reports 27 pathologically verified AD cases among 31 clinically diagnosed cases in the full autopsy sample—about 87%, rather than approximately 80%. The paper supports the general point that most clinical AD diagnoses were confirmed at autopsy, but its estimate comes from Framingham participants who donated their brains, not clinical AD cases generally. (LLM, conf=0.85)

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  • Focal collections of perivascular NFTs in the depths of cortical sulci in CTE differ substantially from PHF-tau pathology of the Alzheimer type reported in cognitively normal young adults, opiate abusers, and non-demented elderly subjects.

    “The focal collections of perivascular NFTs in the depths of the cortical sulci in CTE [65, 66, 126–128] differ substantially from PHF-tau pathology of the Alzheimer type reported in some cognitively normal young adults [15], opiate abusers [4], and non-demented elderly subjects such as those in the Framingham Heart Study [6] or Honolulu Asian Aging Study [67, 194].”

    From The neuropathology of sport (2014) · cites this paper as [6]

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Research works printed but not linked: 4

  1. [13]Roman GC Tatemichi TK Erkinjuntti T Cummings JL Masdeu JC Garcia JH Vascular dementia: diagnostic criteria for research studies. Report of the NINDS-AIREN International Workshop Neurology 43 2 250 60 1993 8094895
  2. [32]Bennett DA Schneider JA Aggarwal NT Arvanitakis Z Shah R Kelly JF Pathologic confirmation of AD diagnoses in longitudinal, epidemiologic studies Alzheimer's Association International Conference on Prevention of Dementia Washington, DC 2005
  3. [72]Savva GM Wharton SB Ince PG Forster G Matthews FE Brayne C Age, neuropathology, and dementia N Engl J Med 360 2302 2309 2009 19474427
  4. [73]Bennett DA Schneider JA Bienias JL Evans DA Wilson RS Mild cognitive impairment is related to Alzheimer disease pathology and cerebral infarctions Neurology 64 834 841 2005 15753419

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Authors
Au, R., Seshadri, S., Knox, K., Beiser, A., J. Himali, J., J. Cabral, H., Auerbach, S., C. Green, R., A. Wolf, P., & C. McKee, A.
Affiliations
  • Boston University (US)
  • Framingham Heart Study (US)
ORCID
Venue
Current Alzheimer Research
Publisher
Bentham Science Publishers Ltd.
Published
2012-06-01
Volume
9
Issue
6
Pages
673-686
ISSN
1567-2050 (ISSN-L)
DOI
10.2174/156720512801322609
PMC
PMC3622706
OpenAlex
W2138784510
Cited by
65
References
81
Citations by year
2026: 5 · 2025: 7 · 2024: 4 · 2023: 7 · 2022: 7 · 2021: 5 · 2020: 5 · 2019: 3 · 2018: 4 · 2017: 4 · 2016: 2 · 2015: 3 · 2014: 5 · 2013: 2 · 2012: 1
FWCI
2.50
Type
journal article
Language
en
Open access
Locations
  • Current Alzheimer Research (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • U.S. Department of Veterans Affairs
  • National Institute on Aging (AG-16495, R01AG031287, AG031287, AG08122, AG033193, R01AG016495, P30AG013846, R01AG033193, R01AG008122, P30-AG13846))
  • National Institute of Neurological Disorders and Stroke (NS17950, R01NS017950)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
Keywords
Alzheimer's disease pathology, brain donation, Framingham Heart Study, sensitivity and specificity, dementia with Lewy bodies, neurofibrillary tangles, mild cognitive impairment, dementia, vascular pathology, ischemic injury, Clinical Dementia Rating
MeSH terms
Aged, 80 and over, Alzheimer Disease, Brain, Cognition, Dementia, Humans, Neuropsychological Tests, Tissue and Organ Procurement, Sensitivity and Specificity

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