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Cited by 516Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsNeurological Disease Mechanisms and Treatments

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Alzheimer Neuropathologic Alterations in Aged Cognitively Normal Subjects

Davis, D G, Schmitt, F A, Wekstein, D R, Markesbery, W R·1999·Journal of Neuropathology and Experimental Neurology
DOI 10.1097/00005072-199904000-00008
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Abstract

The histopathologic changes distinguishing early Alzheimer disease (AD) from normal or pathologic aging are not clearly defined. This report describes the autopsy findings of 59 elderly, well-educated, volunteers. They were examined longitudinally with mental status testing, some for up to 8 years, as part of our normal aging study. This study reveals that (1) the brains of many subjects who did not show cognitive impairment on neuropsychologic testing contain abundant senile plaques (SP) and/or neurofibrillary tangles (NFT); (2) 29 subjects met Khachaturian criteria for AD, 15 met CERAD and 7 met National Institute on Aging-Reagan Institute guidelines; (3) Braak and Braak staging method included 9 in stage IV subjects, 4 in stage V, and 1 in stage VI; (4) there was a progression of NFT from entorhinal cortex to hippocampus and amygdala as a function of age; (5) 2 subjects met criteria for a diagnosis of dementia with Lewy bodies but were not demented; (6) cerebral amyloid angiopathy was present in leptomeningeal vessels in 75% of subjects and in parenchymal vessels in 62% of subjects; (7) only 10 of 59 subjects (17%) had no or few degenerative brain changes. Our study demonstrates that the brains of a large percentage of cognitively normal, relatively well-educated individuals contain numerous degenerative changes and only a small percentage are relatively free of these changes.

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  1. [1]1. Mirra SS, Heyman A, McKeel D, et al. The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part II. Standardization of the ncuropathologic assessment of Alzheimer's disease. Neurology1991;41:479-86
  2. [2]2. The National Institute on Aging and Reagan Institute Working Group. Consensus recommendations for the postmortem diagnosis of Alzheimer's discase. Neurobiol Aging 1997;18:S1–S2
  3. [3]3. Berg L, McKeel D, Miller JP, Baty J, Morris JC. Neuropathological indexes of Alzheimer's disease in demented and nondemented persons aged 80 years and older. Arch Neurol 1993;50:349–58
  4. [4]4. Berg L, McKeel DW, Miller JP, et al. Clinicopathologic studies in cognitively healthy aging and Alzheimer disease: Relation of histologic markers to dementia severity, age, sex, and apolipoprotein E genotype. Arch Neurol 1998;55:326–35
  5. [5]5. Bouras C. Hof PR, Giannakopoulos P. Michel JP, Morrison JH. Regional distribution of neurofibrillary tangles and senile plaques in the cerebral cortex of elderly patients: a quantitative evaluation of a one-year autopsy population from a geriatric hospital. Cereb Cortex 1994;4:138–50
  6. [6]6. Crystal HA, Dickson DW, Sliwinski MJ, et al. Pathological markers associated with normal aging and dementia in the elderly. Ann Neurol 1993;34:566-73
  7. [7]7. Giannakopoulos P, Hof PR, Mottier S, Michel JP, Bouras C. Neuropathological changes in the cerebral cortex of 1258 cases from a geriatric hospital: Retrospective clinicopathological evaluation of a 10-year autopsy population. Acta Neuropathol 1994;87:456–68
  8. [10]10. Morris JC. Storandt M. MeKeel DW, et al. Cerebral amyloid deposition and difuse plaques in "normal" aging: evidence for presymptomatie and very mild Alzheimer's disease. Neurology 1996; 46:707-19
  9. [11]11. Perry EK, Tomlinson BE, Blessed G, Bergmann K, Gibson P, Perry RH. Correlation of cholinergic abnormalities with senile plaques and mental test scores in senile dementia. Br Med J 1978;2:1457–59
  10. [12]12. Haroutunian V, Perl DP, Purohit DP, et al. Regional distribution of neuritic plaques in the nondemented elderly and subjects with very mild Alzheimer discase. Arch Neurol 1998;55:1185–91
  11. [13]13. Sparks DL, Scheff SW, Liu H, Landers TM, Coyne CM, Hunsaker JC. Increased incidence of neurofibrillary tangles (NFT) in nondemented individuals with hypertension, J Neurol Sci 1995;131: 162-69
  12. [14]14. Sparks DL, Hunsaker JC, Scheff SW, Kryscio RJ, Henson JL, Markesbery WR. Cortical senile plaques in coronary artery disease, aging and Alzleiner's disease, Neurobiol Aging 1990;11:601–7
  13. [15]15. Sparks DL, Liu H, Scheff SW, Coyne CM, Hunsaker JC. Temporal sequence of plaque formation in cerebral cortex of non-demented individuals. J Neuropathol Exp Neurol 1993;52:135–42
  14. [16]16. Soneira CF, Scott TM. Severe cardiovascular disease and Alzheimer's disease. Clin Anat 1996;9:118–27
  15. [17]17. Hulette CM, Welsh-Bohmer KA, Murray MG, ct al. Neuropathological and neuropsychological changes in "normal" aging: Evidence for preclinical Alzheimer disease in cognitively normal individuals. J Neuropathol Exp Neurol 1998;57:1 168–74
  16. [18]18. Kazec AM, Eskin TA, Lapham LW, Gabriel KR, McDanicl KD, Hamill RW. Clinicopathologic correlates in Alzheimer's discase: Assessment of clinical and pathologic diagnostic criteria. Alzheimer Dis Assoc Disord 1993;7:152–64
  17. [20]20. Braak H, Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 1991;82:239–59
  18. [27]27. Itoh Y, Yamada M, Yoshida R, et al. Dementia characterized by abundant neurofibrillary tangles and scarce senile plaques: A quantitative pathological study. Eur Neurol 1996;36:94–97
  19. [28]28. Ikeda K, Akiyama H, Ari T, et al. A subset of senile dementia with high incidence of the apolipoprotcin Ee2 allele. Ann Neurol 1997; 41:693-95
  20. [29]29. Boncher C, Jellinger KA. Neurofibrillary tangle predominant form of senile dementia of Alzheimer type: A rare subtype in very old subjects, Acta Neuropathol 1994;88:565–70
  21. [30]30. Ulrich J. Spillantini MG, Gocdert M, Dukas L, Stahelin HB. Abundant neurofbrillary tangles without senile plaques in a subset of patients with senile dementia. Neurodegencration 1992;1:257–64
  22. [31]31. Samuel W, Galasko D, Masliah E, Hansen LA. Neocortical Lewy body counts correlate with dementia in the Lewy body variant of Alzheimer's disease. J Neuropathol Exp Neurol 1996;55:44–52
  23. [33]33. Snowdon DA, Greiner LH, Mortimer JA, Riley KP, Greiner PA. Markesbery WR. Brain infarction and the clinical expression of Alzheimer Discase. JAMA 1997;277:813–17
  24. [34]34. Nagy Z. Esri ME, Jobst KA, et al. The effects of additional pathology on the cognitive deficit in Alzheimer disease. J Neuropathol Exp Neurol 1997;56:165-70
  25. [35]35. Braak H, Braak E. Cortical and subeortical argyrophilic grains characterize a disease associated with adult onset dementia. Neuropathol Appl Neurobiol 1989;15:13–26
  26. [36]36. Braak H. Braak E. Argyrophilic grains: Claracteristic pathology of the cerebral cortex in cases of adult onset deinentia without Alzheimer changes. Neurosci Lett 1987;76:124–27
  27. [38]38. Davis DG. Ross GW, Petrovitch H. et al. Quantitation of argyrophilic grains in hippocampal CA-I of aged Japanese-American males. (Abstract) J Neuropathol Exp Neurol 1997;56:587
  28. [21]21. Braak H, Braak E: Pathology of Alzheimer's discase, In: Calne DB, 40. Esiri MM, Wilcock GK. Cerebral amyloid angiopathy in dementia ed. Neurodegenerative diseases. Philadelphia: W.B. Saunders,1994: and old age. J Neurol Neurosurg Psychiatry 1986;49:1221–26 585-614
  29. [22]22. Khachaturian ZS. Diagnosis of Alzheinier's disease. Areh Neurol 1985;42:1097–1105
  30. [23]23. MeKeith IG, Galasko D, Kosaka K, et al. Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): Report of the consortium on DLB international workshop. Neurology 1996;47:1113-24
  31. [24]24. Morrison JH, Hof PR. Life and death of neurons in the aging brain. Science 1997;278:412–19
  32. [25]25. Geddes JW, Snowdon DA, Soultanian NS, et al. Braak stages IIIIV of Alzheimer-related neuropathology are associated with dementia: Findings from the Nun study. (Abstract) J Neuropathol Exp Neurol 1996;55:617
  33. [39]39. Tolnay M, Schwietert M, Monsch AU, Staehelin HB, Langui D, Probst A. Argyrophilic grain disease: Distribution of grains in patients with and without dementia. Acta Neuropathol 1997;94:353–58
  34. [41]41. Masuda J, Tanaka K, Ueda K, Omae T. Autopsy study of incidence and distribution of cerebral amyloid angiopathy in Hisayama Japan. Stroke 1988;19:205–10
  35. [42]42. Wu E, Lipton RB, Dickson DW. Amyloid angiopathy in diffuse Lewy body discase. Neurology 1992;42:2131–35
  36. [43]43. Yamada M, Tsukagoshi H, Otomo E, Hayakawa M. Cerebral amyloid angiopathy in the aged. J Neurol 1987;234:371–76
  37. [44]44. Schofield P. Mayeux R. Alzhcimer's disease; Clinical features, diagnosis and epidemiology. In: Markesbery WR, ed. Neuropathology of dementing disorders. London: Edward Arnold;1998:89–105 Received November 9, 1998 Revision reccived January 19, 1999 Accepted January 21, 1999

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Metadata

Authors
Davis, D. G., Schmitt, F. A., Wekstein, D. R., & Markesbery, W. R.
Affiliations
University of Kentucky HealthCare (US)
Corresponding author
Davis, D G
ORCID
Schmitt, F A
Venue
Journal of Neuropathology and Experimental Neurology
Publisher
Oxford University Press (OUP)
Published
1999-04
Volume
58
Issue
4
Pages
376-388
ISSN
0022-3069 (ISSN-L)
DOI
10.1097/00005072-199904000-00008
OpenAlex
W2009882167
Cited by
516
References
0
Citations by year
2026: 2 · 2025: 6 · 2024: 6 · 2023: 12 · 2022: 7 · 2021: 13 · 2020: 14 · 2019: 16 · 2018: 22 · 2017: 16 · 2016: 26 · 2015: 18 · 2014: 30 · 2013: 25 · 2012: 19
FWCI
15.68
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Neuropathology & Experimental Neurology (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute on Aging (P50AG005144, P50-AGO5144, 1PO1-AGO51195)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
Keywords
Alzheimer's disease, normal aging, amyloid plaques, neurofibrillary tangles, Braak staging, dementia with Lewy bodies, cerebral amyloid angiopathy, entorhinal cortex, hippocampus, amygdala, neuropathology
MeSH terms
Aged, Aged, 80 and over, Aging, Alzheimer Disease, Amyloidosis, Apolipoproteins E, Brain, Cerebral Infarction, Chronic Disease, Cognition, Female, Genotype, Craniocerebral Trauma, Humans, Male, Mental Status Schedule, Middle Aged, Dementia, Vascular, Silver Staining, Lewy Bodies, Neurofibrillary Tangles

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