The framingham brain donation program: Neuropathology along the cognitive continuum

Rhoda Au, Sudha Seshadri, Kristen Knox, Alexa Beiser, Jayandra J. Himali, Howard J. Cabral, Sanford Auerbach, Robert C. Green, Philip A. Wolf, Ann C. Mckee

Research output: Contribution to journalArticle

27 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)673-686
Number of pages14
JournalCurrent Alzheimer Research
Volume9
Issue number6
DOIs
StatePublished - Jan 1 2012
Externally publishedYes

Fingerprint

Dementia
Brain
Pathology
Blood Vessels
Lewy Body Disease
Neurofibrillary Tangles
Aptitude
Frontal Lobe
Neuropathology
Stroke
Interviews
Sensitivity and Specificity
Wounds and Injuries

Keywords

  • Alzheimer's disease
  • Autopsy
  • Brain
  • Brain ischemia
  • Epidemiology

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

The framingham brain donation program : Neuropathology along the cognitive continuum. / Au, Rhoda; Seshadri, Sudha; Knox, Kristen; Beiser, Alexa; Himali, Jayandra J.; Cabral, Howard J.; Auerbach, Sanford; Green, Robert C.; Wolf, Philip A.; Mckee, Ann C.

In: Current Alzheimer Research, Vol. 9, No. 6, 01.01.2012, p. 673-686.

Research output: Contribution to journalArticle

Au, R, Seshadri, S, Knox, K, Beiser, A, Himali, JJ, Cabral, HJ, Auerbach, S, Green, RC, Wolf, PA & Mckee, AC 2012, 'The framingham brain donation program: Neuropathology along the cognitive continuum', Current Alzheimer Research, vol. 9, no. 6, pp. 673-686. https://doi.org/10.2174/156720512801322609
Au, Rhoda ; Seshadri, Sudha ; Knox, Kristen ; Beiser, Alexa ; Himali, Jayandra J. ; Cabral, Howard J. ; Auerbach, Sanford ; Green, Robert C. ; Wolf, Philip A. ; Mckee, Ann C. / The framingham brain donation program : Neuropathology along the cognitive continuum. In: Current Alzheimer Research. 2012 ; Vol. 9, No. 6. pp. 673-686.
@article{15d983d9ea8e484c96b564f331364fbb,
title = "The framingham brain donation program: Neuropathology along the cognitive continuum",
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.",
keywords = "Alzheimer's disease, Autopsy, Brain, Brain ischemia, Epidemiology",
author = "Rhoda Au and Sudha Seshadri and Kristen Knox and Alexa Beiser and Himali, {Jayandra J.} and Cabral, {Howard J.} and Sanford Auerbach and Green, {Robert C.} and Wolf, {Philip A.} and Mckee, {Ann C.}",
year = "2012",
month = "1",
day = "1",
doi = "10.2174/156720512801322609",
language = "English (US)",
volume = "9",
pages = "673--686",
journal = "Current Alzheimer Research",
issn = "1567-2050",
publisher = "Bentham Science Publishers B.V.",
number = "6",

}

TY - JOUR

T1 - The framingham brain donation program

T2 - Neuropathology along the cognitive continuum

AU - Au, Rhoda

AU - Seshadri, Sudha

AU - Knox, Kristen

AU - Beiser, Alexa

AU - Himali, Jayandra J.

AU - Cabral, Howard J.

AU - Auerbach, Sanford

AU - Green, Robert C.

AU - Wolf, Philip A.

AU - Mckee, Ann C.

PY - 2012/1/1

Y1 - 2012/1/1

N2 - 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.

AB - 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.

KW - Alzheimer's disease

KW - Autopsy

KW - Brain

KW - Brain ischemia

KW - Epidemiology

UR - http://www.scopus.com/inward/record.url?scp=84863546810&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84863546810&partnerID=8YFLogxK

U2 - 10.2174/156720512801322609

DO - 10.2174/156720512801322609

M3 - Article

C2 - 22471865

AN - SCOPUS:84863546810

VL - 9

SP - 673

EP - 686

JO - Current Alzheimer Research

JF - Current Alzheimer Research

SN - 1567-2050

IS - 6

ER -