Role of the Neuropathology of Alzheimer Disease in Dementia in the Oldest-Old | Dementia and Cognitive Impairment | JAMA Neurology | JAMA Network
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1.
Haroutunian  VDavies  PVianna  CBuxbaum  JDPurohit  DP Tau protein abnormalities associated with the progression of Alzheimer disease type dementia.  Neurobiol Aging 2007;28 (1) 1- 7PubMedGoogle Scholar
2.
Nelson  PTJicha  GASchmitt  FA  et al.  Clinicopathologic correlations in a large Alzheimer disease center autopsy cohort: neuritic plaques and neurofibrillary tangles “do count” when staging disease severity.  J Neuropathol Exp Neurol 2007;66 (12) 1136- 1146PubMedGoogle Scholar
3.
Morris  JCStorandt  MMiller  JP  et al.  Mild cognitive impairment represents early-stage Alzheimer disease.  Arch Neurol 2001;58 (3) 397- 405PubMedGoogle Scholar
4.
Haroutunian  VPurohit  DPPerl  DP  et al.  Neurofibrillary tangles in nondemented elderly subjects and mild Alzheimer disease.  Arch Neurol 1999;56 (6) 713- 718PubMedGoogle Scholar
5.
Haroutunian  VPerl  DPPurohit  DP  et al.  Regional distribution of neuritic plaques in the nondemented elderly and subjects with very mild Alzheimer disease.  Arch Neurol 1998;55 (9) 1185- 1191PubMedGoogle Scholar
6.
Braak  HBraak  E Frequency of stages of Alzheimer-related lesions in different age categories.  Neurobiol Aging 1997;18 (4) 351- 357PubMedGoogle Scholar
7.
von Gunten  AKovari  ERivara  CBBouras  CHof  PRGiannakopoulos  P Stereologic analysis of hippocampal Alzheimer's disease pathology in the oldest-old: evidence for sparing of the entorhinal cortex and CA1 field.  Exp Neurol 2005;193 (1) 198- 206PubMedGoogle Scholar
8.
Bussière  TGold  GKovari  E  et al.  Stereologic analysis of neurofibrillary tangle formation in prefrontal cortex area 9 in aging and Alzheimer's disease.  Neuroscience 2003;117 (3) 577- 592PubMedGoogle Scholar
9.
Khachaturian  ZS  Diagnosis of Alzheimer's disease.  Arch Neurol 1985;42 (11) 1097- 1105PubMedGoogle Scholar
10.
Mirra  SSHeyman  A McKeel  D  et al.  The Consortium to Establish a Registry for Alzheimer Disease (CERAD), part II: standardization of the neuropathologic assessment of Alzheimer's disease.  Neurology 1991;41 (4) 479- 486PubMedGoogle Scholar
11.
National Institute on Aging and Reagan Institute Working Group on Diagnostic Criteria for the Neuropathological Assessment of Alzheimer's Disease, Consensus recommendations for the postmortem diagnosis of Alzheimer's disease.  Neurobiol Aging 1997;18 ((suppl 4)) S1- S2PubMedGoogle Scholar
12.
Blessed  GTomlinson  BERoth  M The association between quantitative measures of dementia and of senile change in the cerebral grey matter of elderly subjects.  Br J Psychiatry 1968;114 (512) 797- 811PubMedGoogle Scholar
13.
Tomlinson  BEBlessed  GRoth  M Observations on the brains of demented old people.  J Neurol Sci 1970;11 (3) 205- 242PubMedGoogle Scholar
14.
US Census Bureau, Population Division, US Population projections: national population projects: II, detailed files. http://www.census.gov/population/www/projections/natdet-D1A.html. Accessed June 13, 2008
15.
Hebert  LEScherr  PABienias  JLBennett  DAEvans  DA Alzheimer disease in the US population: prevalence estimates using the 2000 census.  Arch Neurol 2003;60 (8) 1119- 1122PubMedGoogle Scholar
16.
von Strauss  EViitanen  MDe Ronchi  DWinblad  BFratiglioni  L Aging and the occurrence of dementia: findings from a population-based cohort with a large sample of nonagenarians.  Arch Neurol 1999;56 (5) 587- 592PubMedGoogle Scholar
17.
Hebert  LEScherr  PABeckett  LA  et al.  Age-specific incidence of Alzheimer's disease in a community population.  JAMA 1995;273 (17) 1354- 1359PubMedGoogle Scholar
18.
Miech  RABreitner  JCZandi  PPKhachaturian  ASAnthony  JCMayer  L Incidence of AD may decline in the early 90s for men, later for women: the Cache County study.  Neurology 2002;58 (2) 209- 218PubMedGoogle Scholar
19.
Langa  KMChernew  MEKabeto  MU  et al.  National estimates of the quantity and cost of informal caregiving for the elderly with dementia.  J Gen Intern Med 2001;16 (11) 770- 778PubMedGoogle Scholar
20.
Börjesson-Hanson  AGustafson  DSkoog  I Five-year mortality in relation to dementia and cognitive function in 95-year-olds.  Neurology 2007;69 (22) 2069- 2075PubMedGoogle Scholar
21.
Head  ECorrada  MMKahle-Wrobleski  K  et al.  Synaptic proteins, neuropathology, and cognitive status in the oldest-old [published online ahead of print November 12, 2007].  Neurobiol Aging PubMed10.1016/j.neurobiolaging.2007.10.001PubMedGoogle Scholar
22.
Kawas  CHCorrada  MM Alzheimer's and dementia in the oldest-old: a century of challenges.  Curr Alzheimer Res 2006;3 (5) 411- 419PubMedGoogle Scholar
23.
Polvikoski  TSulkava  RMyllykangas  L  et al.  Prevalence of Alzheimer's disease in very elderly people: a prospective neuropathological study.  Neurology 2001;56 (12) 1690- 1696PubMedGoogle Scholar
24.
Silver  MHNewell  KBrady  CHedley-White  ETPerls  TT Distinguishing between neurodegenerative disease and disease-free aging: correlating neuropsychological evaluations and neuropathological studies in centenarians.  Psychosom Med 2002;64 (3) 493- 501PubMedGoogle Scholar
25.
Silver  MNewell  KHyman  BGrowdon  JHedley-Whyte  ETPerls  T Unraveling the mystery of cognitive changes in old age: correlation of neuropsychological evaluation with neuropathological findings in the extreme old.  Int Psychogeriatr 1998;10 (1) 25- 41PubMedGoogle Scholar
26.
Ebly  EMParhad  IMHogan  DBFung  TS Prevalence and types of dementia in the very old: results from the Canadian Study of Health and Aging.  Neurology 1994;44 (9) 1593- 1600PubMedGoogle Scholar
27.
Giannakopoulos  PHof  PRKovari  EVallet  PGHerrmann  FRBouras  C Distinct patterns of neuronal loss and Alzheimer's disease lesion distribution in elderly individuals older than 90 years.  J Neuropathol Exp Neurol 1996;55 (12) 1210- 1220PubMedGoogle Scholar
28.
Giannakopoulos  PHof  PRVallet  PGGiannakopoulos  ASCharnay  YBouras  C Quantitative analysis of neuropathologic changes in the cerebral cortex of centenarians.  Prog Neuropsychopharmacol Biol Psychiatry 1995;19 (4) 577- 592PubMedGoogle Scholar
29.
Giannakopoulos  PHof  PRGiannakopoulos  ASHerrmann  FRMichel  JPBouras  C Regional distribution of neurofibrillary tangles and senile plaques in the cerebral cortex of very old patients.  Arch Neurol 1995;52 (12) 1150- 1159PubMedGoogle Scholar
30.
Prohovnik  IPerl  DPDavis  KLLibow  LLesser  GHaroutunian  V Associations of neuropathology with severity of dementia in late-onset Alzheimer's disease.  Neurology 2006;66 (1) 49- 55PubMedGoogle Scholar
31.
Mirra  SSVogel  FSHeyman  A Guide to the CERAD Protocol for the Neuropathological Assessment of Alzheimer's Disease.  Durham, NC CERAD1987;
32.
Fillenbaum  GGPeterson  BMorris  JCConsortium to Establish a Registry for Alzheimer's Disease, Estimating the validity of the Clinical Dementia Rating scale:the CERAD experience.  Aging (Milano) 1996;8 (6) 379- 385PubMedGoogle Scholar
33.
Morris  JCErnesto  CSchafer  K  et al.  Clinical dementia rating training and reliability in multicenter studies: the Alzheimer's Disease Cooperative Study experience.  Neurology 1997;48 (6) 1508- 1510PubMedGoogle Scholar
34.
Morris  JC The Clinical Dementia Rating (CDR): current version and scoring rules.  Neurology 1993;43 (11) 2412- 2414PubMedGoogle Scholar
35.
Dooneief  GMarder  KTang  MXStern  Y The Clinical Dementia Rating scale: community-based validation of ‘profound' and ‘terminal' stages.  Neurology 1996;46 (6) 1746- 1749PubMedGoogle Scholar
36.
Giannakopoulos  PHof  PRBouras  C Dementia lacking distinctive histopathology: clinicopathological evaluation of 32 cases.  Acta Neuropathol 1995;89 (4) 346- 355PubMedGoogle Scholar
37.
Crystal  HADickson  DDavies  PMasur  DGrober  ELipton  RB The relative frequency of “dementia of unknown etiology” increases with age and is nearly 50% in nonagenarians.  Arch Neurol 2000;57 (5) 713- 719PubMedGoogle Scholar
38.
Crystal  HDickson  DFuld  P  et al.  Clinico-pathologic studies in dementia: nondemented subjects with pathologically confirmed Alzheimer's disease.  Neurology 1988;38 (11) 1682- 1687PubMedGoogle Scholar
39.
Imhof  AKovari  EVon Gunten  A  et al.  Morphological substrates of cognitive decline in nonagenarians and centenarians: a new paradigm?  J Neurol Sci 2007;257 (1-2) 72- 79PubMedGoogle Scholar
40.
Terry  RDMasliah  ESalmon  DP  et al.  Physical basis of cognitive alterations in Alzheimer's disease: synapse loss is the major correlate of cognitive impairment.  Ann Neurol 1991;30 (4) 572- 580PubMedGoogle Scholar
41.
Scheff  SWPrice  DASchmitt  FAMufson  EJ Hippocampal synaptic loss in early Alzheimer's disease and mild cognitive impairment.  Neurobiol Aging 2006;27 (10) 1372- 1384PubMedGoogle Scholar
42.
Giannakopoulos  PGold  GKovari  E  et al.  Assessing the cognitive impact of Alzheimer disease pathology and vascular burden in the aging brain: the Geneva experience.  Acta Neuropathol 2007;113 (1) 1- 12PubMedGoogle Scholar
43.
Snowden  JSNeary  DMann  DM Frontotemporal dementia.  Br J Psychiatry 2002;180140- 143Google Scholar
44.
Stern  Y Cognitive reserve and Alzheimer disease.  Alzheimer Dis Assoc Disord 2006;20 (3) ((suppl 2)) S69- S74PubMedGoogle Scholar
Original Contribution
September 2008

Role of the Neuropathology of Alzheimer Disease in Dementia in the Oldest-Old

Author Affiliations

Author Affiliations: Departments of Psychiatry (Drs Haroutunian, Schnaider-Beeri, Schmeidler, Perl, Maroukian, and Grossman and Mr Wysocki), Pathology (Drs Purohit and Perl), and Geriatrics and Adult Development (Drs Libow and Lesser), Mount Sinai School of Medicine, New York, New York; Department of Psychiatry, Bronx VA Medical Center, Bronx, New York (Drs Haroutunian and Grossman); and Jewish Home and Hospital, New York, New York (Drs Haroutunian and Libow).

Arch Neurol. 2008;65(9):1211-1217. doi:10.1001/archneur.65.9.1211
Abstract

Background  Neuritic plaques (NPs) and neurofibrillary tangles (NFTs) in the brain, especially in the hippocampus, entorhinal cortex, and isocortex, are hallmark lesions of Alzheimer disease and dementia in the elderly. However, this association has not been extensively studied in the rapidly growing population of the very old.

Objective  To assess the relationship between estimates of cognitive function and NP and NFT pathologic conditions in 317 autopsied persons aged 60 to 107 years.

Design  We studied the relationship between severity of dementia and the density of these characteristic lesions of Alzheimer disease in young-old, middle-old, and oldest-old persons. The relationship of the severity of dementia as measured by the Clinical Dementia Rating scale to the density of NPs and NFTs was then assessed in each age group.

Participants  Three hundred seventeen brains of persons aged 60 years and older were selected to have either no remarkable neuropathological lesions or only NP and NFT lesions. Brains with any other neuropathological conditions, either alone or in addition to Alzheimer disease findings, were excluded. The study cohort was then stratified into the youngest quartile (aged 60-80 years), middle 2 quartiles (aged 81-89 years), and oldest quartile (aged 90-107 years).

Results  While the density of NPs and NFTs rose significantly by more than 10-fold as a function of the severity of dementia in the youngest-old group, significant increases in the densities of NPs and NFTs were absent in the brains of the oldest-old. This lack of difference in the densities of NPs and NFTs was due to reduced lesion densities in the brains of oldest-old persons with dementia rather than to increased density of these lesions in the brains of nondemented oldest-old persons.

Conclusions  These findings suggest that the neuropathological features of dementia in the oldest-old are not the same as those of cognitively impaired younger-old persons and compel a vigorous search for neuropathological indices of dementia in this most rapidly growing segment of the elderly population.

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