The DOI matches its Crossref record.
Alzheimer Neuropathologic Alterations in Aged Cognitively Normal Subjects
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Decades of clinical-pathological correlative studies, now corroborated by a decade of neuroimaging studies, also demonstrate a sizable percentage of the non-demented elderly have plaques [40, 51, 54, 55, 58–68].”
From Brain aging, Alzheimer's disease, and mitochondria (2011) · cites this paper as [60]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
The publisher hasn’t deposited this paper’s reference list.
Research works printed but not linked: 37
- [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. 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. 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. 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. 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. 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. 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
- [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
- [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
- [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
- [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
- [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
- [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
- [16]16. Soneira CF, Scott TM. Severe cardiovascular disease and Alzheimer's disease. Clin Anat 1996;9:118–27
- [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
- [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
- [20]20. Braak H, Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 1991;82:239–59
- [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
- [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
- [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
- [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
- [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
- [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
- [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
- [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
- [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
- [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
- [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
- [22]22. Khachaturian ZS. Diagnosis of Alzheinier's disease. Areh Neurol 1985;42:1097–1105
- [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
- [24]24. Morrison JH, Hof PR. Life and death of neurons in the aging brain. Science 1997;278:412–19
- [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
- [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
- [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
- [42]42. Wu E, Lipton RB, Dickson DW. Amyloid angiopathy in diffuse Lewy body discase. Neurology 1992;42:2131–35
- [43]43. Yamada M, Tsukagoshi H, Otomo E, Hayakawa M. Cerebral amyloid angiopathy in the aged. J Neurol 1987;234:371–76
- [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
Cited by
Sorted by citations
Items 101–200 of 515
Activation of Caspase-6 in Aging and Mild Cognitive Impairment
Albrecht, S., Bourdeau, M., Bennett, D. A., Mufson, E. J., Bhattacharjee, M. B., & LeBlanc, A. C. (2007) · American Journal Of Pathology · doi:10.2353/ajpath.2007.060974 · Cited by 155
Challenges of multimorbidity of the aging brain: a critical update
Jellinger, K. A., & Attems, J. (2015) · Journal of Neural Transmission · doi:10.1007/s00702-014-1288-x · Cited by 154
“small or large infarctions, lacunes, and white matter lesions, in up to 10 % (Davis et al. 1999; Jentoft et al. 2011; Knopman et al. 2003; Schneider et al. 2009).”
BackgroundInfluentialKim, S., Jeitner, T. M., & Steinert, P. M. (2002) · Neurochemistry International · doi:10.1016/s0197-0186(01)00064-x · Cited by 156
Green, M. S., Kaye, J. A., & Ball, M. J. (2000) · Neurology · doi:10.1212/wnl.54.1.105 · Cited by 152
Aβ as a bioflocculant: implications for the amyloid hypothesis of Alzheimer’s disease
Robinson, S. R., & Bishop, G. M. (2002) · Neurobiology of Aging · doi:10.1016/s0197-4580(01)00342-6 · Cited by 155
Weissberger, G. H., Strong, J. V., Stefanidis, K. B., Summers, M. J., Bondi, M. W., & Stricker, N. H. (2017) · Neuropsychology Review · doi:10.1007/s11065-017-9360-6 · Cited by 169
“In contrast, individuals with normal neuropsychological profiles can be found to be amyloid positive based on amyloid PET or CSF studies and many individuals with pathological diagnoses of AD at autopsy do not carry a clinical diagnosis in life (Davis et al. 1999; Hardy and Selkoe 2002).”
BackgroundArgyrophilic grain disease: A late‐onset dementia with distinctive features among tauopathies
Tolnay, M., & Clavaguera, F. (2004) · Neuropathology · doi:10.1111/j.1440-1789.2004.00591.x · Cited by 154
The Mitochondrial Spiral: An Adequate Cause of Dementia in the Alzheimer's Syndrome
Blass, J. P. (2000) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2000.tb05576.x · Cited by 150
de la Torre, J. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-180004 · Cited by 161
Is aging part of Alzheimer's disease, or is Alzheimer's disease part of aging?
Swerdlow, R. H. (2006) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2006.06.021 · Cited by 154
“[40] Davis DG, Schmitt FA, Wekstein DR, Markesbery WR.”
BackgroundResultAbsence of cognitive impairment or decline in preclinical Alzheimer’s disease
Goldman, W. P., Price, J. L., Storandt, M., Grant, E., McKeel, D. W., Rubin, E. H., & Morris, J. C. (2001) · Neurology · doi:10.1212/wnl.56.3.361 · Cited by 141
Clinicopathological analysis of dementia disorders in the elderly – An update
Jellinger, K. A. (2006) · Journal of Alzheimer s Disease · doi:10.3233/jad-2006-9s308 · Cited by 143
“Similar correlations have been observed in both younger individuals [13,14,19,26] jects [17,21,30],indicating a broad “gray zone” of mild to moderate dementia showing a wide range of neuritic AD lesions (Fig.”
Post-mortem assessment in vascular dementia: advances and aspirations
McAleese, K. E., Alafuzoff, I. I., Charidimou, A., Reuck, J. D., Grinberg, L. T., Hainsworth, A. H., Hortobágyi, T., Ince, P. G., Jellinger, K. A., Gao, J., et al. (2016) · BMC Medicine · doi:10.1186/s12916-016-0676-5 · Cited by 144
“Haemorrhagic infarcts can occur in infarcted regions in which the remaining vessels have fragile vessel walls as a result of SVD or CAA, or they may be caused by venous obstruction; less commonly, haemorrhagic infarcts in the brain can be caused by collateral blood influx into an infarcted area [7].”
BackgroundInfluentialOrbitofrontal cortex pathology in Alzheimer's disease.
van Hoesen, G. V., Parvizi, J., & Chu, C.-C. (2000) · Cerebral Cortex · doi:10.1093/cercor/10.3.243 · Cited by 143
“Alzheimer’s disease (AD) is a devastating and unremitting neurodegenerative disease with dementia as a certain outcome (Van Hoesen and Damasio, 1987; Braak and Braak, 1991; Hof and Morrison, 1994; Gómez-Isla and Hyman, 1997; Hof, 1997; Davis et al., 1999).”
Accuracy of clinical criteria for AD in the Honolulu–Asia Aging Study, a population-based study
Petrovitch, H., White, L. R., Ross, G. W., Steinhorn, S. C., Li, C. Y., Masaki, K., Davis, D. G., Nelson, J., Hardman, J. M., Curb, J. D., et al. (2001) · Neurology · doi:10.1212/wnl.57.2.226 · Cited by 136
Self-citationAttems, J., Lintner, F., & Jellinger, K. A. (2004) · Acta Neuropathologica · doi:10.1007/s00401-004-0822-6 · Cited by 139
Ranaivo, H. R., Craft, J. M., Hu, W., Guo, L., Wing, L. K., Eldik, L. J. V., & Watterson, D. M. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.4652-05.2006 · Cited by 137
“Our data are consistent with clinical findings that cognitively intact individuals can have considerable amyloid deposits and that relevant clinicopathological endpoints in the human disease do not correlate directly or solely with the pattern of amyloid plaque deposition (Crystal et al., 1988; Davis et al., 1999; Gui…”
BackgroundResultNovel plasma biomarker surrogating cerebral amyloid deposition
KANEKO, N., Nakamura, A., Washimi, Y., Kato, T., Sakurai, T., Arahata, Y., Bundo, M., Takeda, A., Niida, S., Ito, K., et al. (2014) · Proceedings of the Japan Academy Series B · doi:10.2183/pjab.90.353 · Cited by 138
Thal, D. R., Griffin, W. S. T., & Braak, H. (2008) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2008.00411.x · Cited by 134
“the A -load or semiquantitative plaque scores obtained in these regions, does not show significant differences among different degrees of dementia [23–26], between control cases with high amounts of AD-related pathology and AD cases [27–31] and among the levels of brain atrophy [32].”
BackgroundBrain volume change and cognitive trajectories in aging.
Fletcher, E. M., Gavett, B. E., Harvey, D. J., Farias, S. T., Olichney, J., Beckett, L. A., DeCarli, C. S., & Mungas, D. (2018) · Neuropsychology · doi:10.1037/neu0000447 · Cited by 131
Neuropathology of Alzheimer disease: pathognomonic but not pathogenic
Castellani, R. J., Lee, H., Zhu, X., Nunomura, A., Perry, G. L., & Smith, M. A. (2006) · Acta Neuropathologica · doi:10.1007/s00401-006-0071-y · Cited by 133
“everyone at mid-life is on the verge of developing AD, a view also directly contradicted by the fact that a large percentage of cognitively-intact, aged individuals contain amyloid- loads equivalent to patients with AD [15].”
BackgroundAsymptomatic Alzheimers Disease: A Prodrome or a State of Resilience?
Driscoll, I., & Troncoso, J. (2011) · Current Alzheimer Research · doi:10.2174/156720511795745348 · Cited by 130
“Similar observations have subsequently been reported by several different groups over the years [13, 32, 34, 53–58].”
ResultAPOE associations with severe CAA-associated vasculopathic changes: collaborative meta-analysis
Rannikmäe, K., Kalaria, R. N., Greenberg, S. M., Chui, H. C., Schmitt, F. A., Samarasekera, N., Salman, R. A., & Sudlow, C. L. M. (2013) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2013-306485 · Cited by 131
Self-citationDevelopmental and vascular risk factors for Alzheimer's disease
Borenstein, A. R., Wu, Y., Mortimer, J. A., Schellenberg, G. D., McCormick, W. C., Bowen, J. D., McCurry, S. M., & Larson, E. B. (2004) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2004.04.010 · Cited by 127
Wakisaka, Y., Furuta, A., Tanizaki, Y., Kiyohara, Y., Iida, M., & Iwaki, T. (2003) · Acta Neuropathologica · doi:10.1007/s00401-003-0750-x · Cited by 129
“This is similar to senile plaques, which exist in ATD patients and also in some non-demented individuals [ 6 ].”
BackgroundSuicide and Alzheimer’s pathology in the elderly: a case–control study
Rubio, A., Vestner, A. L., Stewart, J. M., Forbes, N. T., Conwell, Y., & Cox, C. (2001) · Biological Psychiatry · doi:10.1016/s0006-3223(00)00952-5 · Cited by 115
“Of importance is the wide range of AD neuropathology among individuals with intact cognition (Davis et al 1999).”
Elman, J. A., Madison, C. M., Baker, S. L., Vogel, J. W., Marks, S. M., Crowley, S., O’Neil, J. P., & Jagust, W. J. (2014) · Cerebral Cortex · doi:10.1093/cercor/bhu259 · Cited by 122
Attems, J., Quass, M., Jellinger, K. A., & Lintner, F. (2007) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2007.01.013 · Cited by 126
Šalković‐Petrišić, M., Barilar, J. O., Grünblatt, E., Riederer, P. F., & Hoyer, S. (2009) · Journal of Alzheimer s Disease · doi:10.3233/jad-2009-1184 · Cited by 122
“Thus, the role of the latter in the causation of sporadic AD remains enigmatic [7,8], all the more so since the brains, in the course of time, of longitudinally examined aged nondemented cognitively normal subjects have been found to contain abundant neuritic plaques and neurofibrillary tangles [9–11].”
BackgroundEngaging in Cognitive Activities, Aging, and Mild Cognitive Impairment: A Population-Based Study
Geda, Y. E., Topazian, H. M., Lewis, R. A., Roberts, R. O., Knopman, D. S., Pankratz, V. S., Christianson, T. J. H., Boeve, B. F., Tangalos, E. G., Ivnik, R. J., et al. (2011) · Journal of Neuropsychiatry · doi:10.1176/jnp.23.2.jnp149 · Cited by 132
Chad, J. A., Pasternak, O., Salat, D. H., & Chen, J. J. (2018) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2018.07.018 · Cited by 114
“A wide variety of debris have been found to accumulate in the aging brain such as amyloid plaques, neurofibrillary tangles and Lewy bodies (Davis et al., 1999; Elobeid et al., 2016; Knopman et al., 2003).”
BackgroundMontine, T. J., Markesbery, W. R., Zackert, W. E., Sanchez, S. C., Roberts, L. J., & Morrow, J. D. (1999) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)65185-1 · Cited by 116
“It is interesting that F2-isoprostane levels correlated with advancing Braak stage but not with increasing tissue density of NPs or NFTs, even though NP and NFT densities increase with increasing Braak stage in AD patients and in nondemented aged individuals.(34) These results may suggest that it is the distribution,…”
BackgroundSelf-citationAssociations of cortical astrogliosis with cognitive performance and dementia status
Kashon, M. L., Ross, G. W., O'Callaghan, J. P., Miller, D. B., Petrovitch, H., Burchfiel, C. M., Sharp, D. S., Markesbery, W. R., Davis, D. G., Hardman, J. M., et al. (2005) · Journal of Alzheimer s Disease · doi:10.3233/jad-2004-6604 · Cited by 115
“Neverthe-less, some post-mortem studies indicate that NPs and NFTs may be present in the brains of clinically normal individuals [6,12,14,26,35,61].”
Self-citationZACCAI, J. H., Ince, P. G., & Brayne, C. (2006) · BMC Neurology · doi:10.1186/1471-2377-6-2 · Cited by 113
“It is increasingly acknowledged that the proportion of normal elderly individuals with a substantial neuropathological burden is not negligible [34,106,113].”
BackgroundAlzheimer?s associated inflammation, potential drug targets and future therapies
Stuchbury, G., & M�nch, G. (2004) · Journal of Neural Transmission · doi:10.1007/s00702-004-0188-x · Cited by 113
“Ab17–42, known as the P3 fragment, is suggested to be relatively harmless, due to the absence of abnormal neuritis and inflammation that usually accompanies senile plaque formation (Dickson, 1997; Wisniewski et al., 1997; Davies et al., 1999).”
BackgroundDing, S., & Hoesen, G. W. V. (2010) · Human Brain Mapping · doi:10.1002/hbm.20940 · Cited by 111
“Neuropathological studies have revealed that PC and its interconnected neural systems are involved in Alzheimer’s disease (AD), Pick’s disease, Down’s syndrome, Parkinson’s disease, progressive supranuclear palsy, dementia with argyrophilic grains, Huntington’s disease, and schizophrenia [Arnold, 2000; Braak and Braak…”
BackgroundCircadian Rhythm and Alzheimer’s Disease
Homolak, J., Mudrovčić, M., Vukić, B., & Toljan, K. (2018) · Medical Sciences · doi:10.3390/medsci6030052 · Cited by 120
Silverberg, G. D., Miller, M. C., Messier, A. A., Majmudar, S., Machan, J. T., Donahue, J. E., Stopa, E. G., & Johanson, C. E. (2009) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e3181c8ad2f · Cited by 111
Silver, M. H., Newell, K. L., Brady, C. B., Hedley-White, E. T., & Perls, T. T. (2002) · Psychosomatic Medicine · doi:10.1097/00006842-200205000-00014 · Cited by 110
“For example, Davis and colleagues (49) found that 15 of 59 cognitively intact persons that came to autopsy met CERAD criteria for AD; furthermore, only 10 of 59 had no senile plaques or neurofibrillary tangles.”
BackgroundSystemic and CNS Inflammation Crosstalk: Implications for Alzheimer’s Disease
Paouri, E., & Georgopoulos, S. (2019) · Current Alzheimer Research · doi:10.2174/1567205016666190321154618 · Cited by 109
Fatty acids, lipid metabolism and Alzheimer pathology
Hooijmans, C. R., & Kiliaan, A. J. (2008) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2007.11.081 · Cited by 115
“However this hypothesis is still under debate because of conflicting results about for example the neurotoxicity of β-amyloid deposition in vivo (Bishop and Robinson, 2002; de la Torre, 2004) and it has been found that also many non-demented persons show large amounts of Alzheimer's disease pathology (Davis et al., 19…”
CSF Aβ42, Tau and phosphorylated Tau, APOE ɛ4 allele and MCI type in progressive MCI
Herukka, S., Helisalmi, S., Hallikainen, M., Tervo, S., Soininen, H. S., & Pirttilä, T. (2006) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2006.02.001 · Cited by 113
Brain pathologies in extreme old age
Neltner, J. H., Abner, E. L., Jicha, G. A., Schmitt, F. A., Patel, E., Poon, L. W., Marla, G., Green, R. C., Davey, A., Johnson, M. A., et al. (2015) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2015.10.009 · Cited by 106
“Pathological assessments were performed at the University of Kentucky on all the cases, and the methodology has been described in detail (Davis, et al., 1999, Nelson, et al., 2009a, Nelson, et al., 2007, Riley, et al., 2002, Wolf, et al., 1999).”
Self-citationOverlapping but distinct TDP‐43 and tau pathologic patterns in aged hippocampi
Smith, V. D., Bachstetter, A. D., Ighodaro, E. T., Roberts, K. N., Abner, E. L., Fardo, D. W., & Nelson, P. T. (2017) · Brain Pathology · doi:10.1111/bpa.12505 · Cited by 105
“Pathological assessments were performed at the UK-ADC using methodology that was described previously including Gallyas silver staining (18, 57, 67, 80).”
Cerebrovascular pathology in Down syndrome and Alzheimer disease
Head, E., Phelan, M. J., Doran, E., Kim, R. C., Poon, W. W., Schmitt, F. A., & Lott, I. T. (2017) · Acta Neuropathologica Communications · doi:10.1186/s40478-017-0499-4 · Cited by 105
“9 years at autopsy) has been reported as high as 62% [17].”
BackgroundSelf-citationAlzheimer's disease: How does it start?
de la Torre, J. C. (2002) · Journal of Alzheimer s Disease · doi:10.3233/jad-2002-4606 · Cited by 102
Aliev, G., Palacios, H. H., Walrafen, B., Lipsitt, A. E., Obrenovich, M. E., & Morales, L. (2009) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2009.03.015 · Cited by 102
Jicha, G. A., & Carr, S. A. (2010) · Journal of Alzheimer s Disease · doi:10.3233/jad-2010-1237 · Cited by 107
“At present, the best data available come from frequency measurement in selected autopsy cohorts of subjects that died with normal cognition [71,79,81,85, 100–107].”
Free radical-mediated damage to brain in Alzheimer's disease and its transgenic mouse models
Sonnen, J. A., Breitner, J. C. S., Lovell, M. A., Markesbery, W. R., Quinn, J. F., & Montine, T. J. (2008) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2008.04.022 · Cited by 107
Self-citationCerebral β-amyloid deposition predicts HIV-associated neurocognitive disorders in APOE ε4 carriers
Soontornniyomkij, V., Moore, D. J., Gouaux, B. D., Soontornniyomkij, B., Tatro, E. T., Umlauf, A., Masliah, E., Levine, A. J., Singer, E. J., Vinters, H. V., et al. (2012) · AIDS · doi:10.1097/qad.0b013e32835a117c · Cited by 102
“The middle–frontal gyrus is one of the isocortex regions having relatively high Ab plaque density [36].”
BackgroundScheff, S. W., Ansari, M. A., & Mufson, E. J. (2016) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2016.02.030 · Cited by 100
Vascular ageing: Underlying mechanisms and clinical implications
Laina, A., Stellos, K., & Stamatelopoulos, K. S. (2017) · Experimental Gerontology · doi:10.1016/j.exger.2017.06.007 · Cited by 106
“Interestingly, the presence of cerebral amyloid angiopathy has been found not only in the brain of patients with AD but also in neurologically healthy aged individuals, as amyloid plaques have been shown in autopsy studies to develop in non-dementia brains (Davis et al., 1999; Arvanitakis et al., 2011).”
BackgroundAmyloid PET in clinical practice: Its place in the multidimensional space of Alzheimer's disease
Vandenberghe, R., Adamczuk, K., Dupont, P., Laere, K. V., & Chételat, G. (2013) · NeuroImage: Clinical · doi:10.1016/j.nicl.2013.03.014 · Cited by 99
“The principal structural changes are: • Loss of synaptic density (Davis et al., 1999; DeKosky and Scheff, 1990; Scheff et al., 2006; Terry et al., 1991), starting in the dentate gyrus and correlated to episodic memory scores (Scheff et al., 2006) • Neuronal loss, starting in entorhinal cortex…”
BackgroundMullane, K., & Williams, M. (2018) · Biochemical Pharmacology · doi:10.1016/j.bcp.2018.09.026 · Cited by 98
Giannakopoulos, P., Gold, G., Kövari, E., von Gunten, A., Imhof, A., Bouras, C., & Hof, P. R. (2006) · Acta Neuropathologica · doi:10.1007/s00401-006-0144-y · Cited by 96
“either very mild memory impairment or even in the absence of cognitive deterioration has been well documented [2, 3, 5, 24, 58, 63, 73, 74, 81, 95].”
BackgroundSeshadri, S., Beiser, A., Au, R., Wolf, P. A., Evans, D. A., Wilson, R. S., Petersen, R. C., Knopman, D. S., Rocca, W. A., Kawas, C. H., et al. (2011) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2010.12.002 · Cited by 97
“Several studies have demonstrated the presence of the neuropathological substrate for AD in the absence of clinical symptoms [45].”
BackgroundIrwin, D. J., Trojanowski, J. Q., & Grossman, M. (2013) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2013.00006 · Cited by 96
“There are several reasons for these discrepancies; first, even in most autopsy-based studies, autopsy data on controls is lacking (Table 1) and a significant proportion of non-demented elderly can have underlying AD neuropathology (Davis et al., 1999), and thus influence CSF analyte measures.”
ResultRodriguez, R. D., Suemoto, C. K., Molina, M., Nascimento, C. F., Leite, R. E. P., Ferretti‐Rebustini, R. E. D. L., Farfel, J. M., Heinsen, H., Nitríni, R., Uéda, K., et al. (2016) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/nlw034 · Cited by 95
“Davis et al found AGD in 23% of a total sample of 59 older cognitively normal subjects (37).”
BackgroundCalcium channelopathies and Alzheimer's disease: Insight into therapeutic success and failures
Chakroborty, S., & Stutzmann, G. E. (2014) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2013.11.012 · Cited by 91
Delayed recall, hippocampal volume and Alzheimer neuropathology
Mortimer, J. A., Gosche, K. M., Riley, K. P., Markesbery, W. R., & Snowdon, D. A. (2004) · Neurology · doi:10.1212/01.wnl.0000106463.66966.65 · Cited by 92
Self-citationNeuropathological approaches to cerebral aging and neuroplasticity
Jellinger, K. A., & Attems, J. (2013) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2013.15.1/kjellinger · Cited by 94
“Cognition and its decline associated with brain aging also seems to be variable and possibly open to modifications.1 Studies in humans and animal models suggest that age-related cognitive decline is more likely to be associated with alterations in synaptic connectivity than with neuronal loss and white matter changes.…”
BackgroundInfluentialPulliam, J. F., Jennings, C. D., Kryscio, R. J., Davis, D. G., Wilson, D., Montine, T. J., Schmitt, F. A., & Markesbery, W. R. (2003) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.10069 · Cited by 89
“Neuropathologic examinations were performed as previously described [Davis et al., 1999].”
MethodSelf-citationBangen, K. J., Restom, K., Liu, T. T., Wierenga, C. E., Jak, A. J., Salmon, D. P., & Bondi, M. W. (2012) · Journal of Alzheimer s Disease · doi:10.3233/jad-2012-120292 · Cited by 92
“Neuropathological studies of cognitively normal older adults suggest that the Alzheimer’s disease (AD)related pathophysiological process begins during a presymptomatic stage of the disease [1, 2].”
Zhang, Z., Li, X., Wang, Z.-H., Song, M., Yu, S. P., Kang, S. S., Liu, X., Zhang, Z., Xie, M., Liu, G., et al. (2018) · Molecular Psychiatry · doi:10.1038/s41380-018-0286-z · Cited by 91
Brain Donation in Normal Aging
Schmitt, F. A., Wetherby, M. M. C., Wekstein, D. R., DEARTH, C., & Markesbery, W. R. (2001) · The Gerontologist · doi:10.1093/geront/41.6.716 · Cited by 87
“A description of the autopsy findings in the first 59 cases in this series has recently been presented (Davis et al., 1999; Schmitt et al., 2000).”
BackgroundSelf-citationCerebral Hypoperfusion, Capillary Degeneration, and Development of Alzheimer Disease
de la Torre, J. C. (2000) · Alzheimer Disease & Associated Disorders · doi:10.1097/00002093-200000001-00012 · Cited by 86
“The brains of many cognitively normal, older individuals show abundant senile plaques (and neurofibrillary tangles) but no signs of AD (Davis et al., 1999).”
BackgroundSelf-reported head injury and risk of late-life impairment and AD pathology in an AD center cohort
Abner, E. L., Nelson, P. T., Schmitt, F. A., Browning, S. R., Fardo, D. W., Wan, L., Jicha, G. A., Cooper, G. E., Smith, C. D., Caban-Holt, A. M., et al. (2014) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000355478 · Cited by 84
Self-citationPrecuneus amyloid burden is associated with reduced cholinergic activity in Alzheimer disease
Ikonomović, M. D., Klunk, W. E., Abrahamson, E. E., Wuu, J., Mathis, C. A., Scheff, S. W., Mufson, E. J., & DeKosky, S. T. (2011) · Neurology · doi:10.1212/wnl.0b013e3182231419 · Cited by 82
Landry, G. J., & Liu-Ambrose, T. (2014) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2014.00325 · Cited by 84
Age and amyloid-related alterations in default network habituation to stimulus repetition
Vannini, P., Hedden, T., Becker, J. A., Sullivan, C., Putcha, D., Rentz, D. M., Johnson, K. A., & Sperling, R. A. (2011) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2011.01.003 · Cited by 86
“This finding is consonant with post-mortem reports of Aβ pathology in approximately 25–40% of normal older adults (Davis et al., 1999; Price and Morris, 1999; Knopman et al., 2003; Bennett et al., 2006).”
ResultLife-course blood pressure in relation to brain volumes
Power, M. C., Schneider, A. L. C., Wruck, L., Griswold, M., Coker, L. H., Alonso, A., Jack, C. R., Knopman, D., Mosley, T. H., & Gottesman, R. F. (2016) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2016.03.012 · Cited by 81
Impact of age-related neuroglial cell responses on hippocampal deterioration
Ojo, J. O., Rezaie, P., Gabbott, P. L. A., & Stewart, M. G. (2015) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2015.00057 · Cited by 83
“It is possible that the underlying accumulation of protein aggregates present in aged brains (Davis et al., 1999) are by-products of an ineffective role of TREM2 dependent signaling in controlling microglia clearance of potentially toxic cellular debris.”
BackgroundLaClair, K. D., Donde, A., Ling, J. P., Jeong, Y. H., Chhabra, R., Martin, L. J., & Wong, P. C. (2016) · Acta Neuropathologica · doi:10.1007/s00401-016-1637-y · Cited by 76
Amyloid and tau PET demonstrate region-specific associations in normal older people
Lockhart, S. N., Schöll, M., Baker, S. L., Ayakta, N., Swinnerton, K. N., Bell, R. K., Mellinger, T. J., Shah, V. D., O’Neil, J. P., Janabi, M., et al. (2017) · NeuroImage · doi:10.1016/j.neuroimage.2017.02.051 · Cited by 80
“In addition to their association with Alzheimer's disease (AD), βamyloid (Aβ) and tau pathologies become increasingly prevalent in the human brain with advanced age (Davis et al., 1999; Bennett et al., 2006).”
BackgroundMartin, S. B., Smith, C. D., Collins, H. R., Schmitt, F. A., & Gold, B. T. (2008) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2008.08.010 · Cited by 84
Self-citationSantaCruz, K. S., Sonnen, J. A., Pezhouh, M. K., Desrosiers, M. F., Nelson, P. T., & Tyas, S. L. (2011) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e31822e8ae9 · Cited by 79
Shioi, J., Georgakopoulos, A., Mehta, P. D., Kouchi, Z., Litterst, C. M., Baki, L., & Robakis, N. K. R. K. (2006) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.04391.x · Cited by 80
Development and validation of a salivary tau biomarker in Alzheimer's disease
Pekeles, H., Qureshi, H. Y., Paudel, H. K., Schipper, H. M., Gornistky, M., & Chertkow, H. M. (2018) · Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring · doi:10.1016/j.dadm.2018.03.003 · Cited by 80
Tremblay, C., Pilote, M., Phivilay, A., Émond, V., Bennett, D. A., & Calon, F. (2007) · Journal of Alzheimer s Disease · doi:10.3233/jad-2007-12411 · Cited by 78
“However, the presence of high A β 40 and A β 42 loads in a few non cognitively impaired subjects supports the notion that A β accumulation is not sufficient to induce cognitive deficit [10,14].”
Negash, S., Bennett, D. A., Wilson, R. S., Schneider, J. A., & Arnold, S. E. (2011) · Current Alzheimer Research · doi:10.2174/156720511795745302 · Cited by 79
“As such, the correlation between neuropathological lesions and cognition is modest and accounts for about a quarter of the variance of cognition among older adults [9–12].”
BackgroundBiomarkers for cognitive impairment and dementia in elderly people
Sonnen, J. A., Montine, K. S., Quinn, J. F., Kaye, J. A., Breitner, J. C. S., & Montine, T. J. (2008) · The Lancet Neurology · doi:10.1016/s1474-4422(08)70162-5 · Cited by 78
Oxidation of Aβ and Plaque Biogenesis in Alzheimer's Disease and Down Syndrome
Head, E., Garzon-Rodriguez, W., Johnson, J. K., Lott, I. T., Cotman, C. W., & Glabe, C. (2001) · Neurobiology of Disease · doi:10.1006/nbdi.2001.0431 · Cited by 75
Jagust, W. J. (2006) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2005.11.002 · Cited by 82
Vascular pathology: Cause or effect in Alzheimer disease?
Rius‐Pérez, S., Tormos, A. M., Pérez, S., & Taléns‐Visconti, R. (2017) · Neurología (English Edition) · doi:10.1016/j.nrleng.2015.07.008 · Cited by 79
Oxidative stress in Alzheimer's disease: Primary villain or physiological by-product?
Sutherland, G. T., Chami, B., Youssef, P., & Witting, P. K. (2013) · Redox Report · doi:10.1179/1351000213y.0000000052 · Cited by 80
Mechanisms of AD neurodegeneration may be independent of Aβ and its derivatives
Robakis, N. K. R. K. (2010) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2010.05.022 · Cited by 72
“Importantly, amyloid depositions at levels similar to those seen in AD are often detected in normal aged individuals (Crystal et al., 1988; Davis et al., 1999), and transgenic (Tg) animal models with high levels of brain amyloid deposits that show no significant neurodegeneration have been reported (Hsia et al.”
BackgroundKrashia, P., Nobili, A., & D’Amelio, M. (2019) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2019.00123 · Cited by 70
“…AD patients can show low Aβ plaque load (Edison et al., 2007; Li et al., 2008), while in the brain of elderly nondemented patients the distribution of Aβ plaques can be as extensive as that of dementia patients (Davis et al., 1999; Fagan et al., 2009; Price et al., 2009; Chételat et al., 2013).”
BackgroundPreclinical AD Workgroup staging: Pathological correlates and potential challenges
Jicha, G. A., Abner, E. L., Schmitt, F. A., Kryscio, R. J., Riley, K. P., Cooper, G. E., Stiles, N., Mendiondo, M. S., Smith, C. D., Van Eldik, L. J., et al. (2012) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2011.02.018 · Cited by 71
Self-citationVascular aspects in Alzheimer’s disease
Skoog, I. (2000) · Advances in Dementia Research · doi:10.1007/978-3-7091-6781-6_6 · Cited by 71
Dementia: Alzheimer pathology and vascular factors: From mutually exclusive to interaction
van Norden, A. G. W., van Dijk, E. J., de Laat, K. F., Scheltens, P., Olde-Rikkert, M. G. M., & de Leeuw, F. (2011) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2011.07.003 · Cited by 75
Ante mortem amyloid imaging and β-amyloid pathology in a case with dementia with Lewy bodies
Kantarci, K., Yang, C., Schneider, J. A., Senjem, M. L., Reyes, D. A., Lowe, V. J., Barnes, L. L., Aggarwal, N. T., Bennett, D. A., Smith, G. E., et al. (2010) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2010.08.007 · Cited by 72
Adav, S. S., & Sze, S. K. (2016) · Molecular Brain · doi:10.1186/s13041-016-0272-9 · Cited by 75
Patología vascular: ¿causa o efecto en la enfermedad de Alzheimer?
Rius‐Pérez, S., Tormos, A. M., Pérez, S., & Taléns‐Visconti, R. (2015) · Neurología · doi:10.1016/j.nrl.2015.07.010 · Cited by 74
“…aguda al da˜no neuronal 29 Además, el grado de deposición del péptido A (cid:2) no se ha podido corre-lacionar con la gravedad de la disfunción cognitiva en los pacientes con EA, e incluso se han hallado deposiciones amiloides en cerebros de muchos individuos con funciones cognitivas normales 30”
Antioxidant protection and neurodegenerative disease: The role of amyloid-β and tau
Castellani, R. J., Lee, H., Perry, G. L., & Smith, M. A. (2006) · American Journal of Alzheimer s Disease & Other Dementias® · doi:10.1177/153331750602100213 · Cited by 72
Prevalence of dementia subtypes in a developing country: a clinicopathological study
Grinberg, L. T., Nitríni, R., Suemoto, C. K., Ferretti‐Rebustini, R. E. D. L., Leite, R. E. P., Farfel, J. M., Santos, E. B., Andrade, M. P., Alho, A. T. D. L., Lima, M. D. C., et al. (2013) · Clinics · doi:10.6061/clinics/2013(08)13 · Cited by 71
“The frequencies of AD and VaD in the control group were similar to those reported in the literature (32,33).”
ResultA amyloid deposition in the language system and how the brain responds
Nelissen, N., Vandenbulcke, M., Fannes, K., Verbruggen, A., Peeters, R. R., Dupont, P. J., Laere, K. V., Bormans, G. M., & Vandenberghe, R. R. (2007) · Brain · doi:10.1093/brain/awm133 · Cited by 70
“Brains from cognitively intact subjects may even show a neuritic plaque load indistinguishable from that seen in brains from patients who died with a diagnosis of dementia (Crystal et al., 1988; Katzman et al., 1988; Troncoso et al., 1996; Davis et al., 1999; Price and Morris, 1999; Neuropathology Group of the Medical…”
BackgroundResultRevisiting the role of brain and peripheral Aβ in the pathogenesis of Alzheimer's disease
Uddin, M. S., Kabir, M. T., Tewari, D., Mamun, A. A., Mathew, B., Aleya, L., Barreto, G. E., Bin-Jumah, M. N., Abdel‐Daim, M. M., & Ashraf, G. M. (2020) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2020.116974 · Cited by 70
Puentes-Díaz, N., Chaparro, D., Morales-Morales, D., Flores-Gaspar, A., & Alí-Torres, J. (2023) · ACS Omega · doi:10.1021/acsomega.2c06939 · Cited by 67
Cause of death in demented and non-demented elderly inpatients; an autopsy study of 308 cases
Attems, J., König, C., Huber, M., et al. (2005) · Journal of Alzheimer s Disease · doi:10.3233/jad-2005-8107 · Cited by 67
“However, in other cohorts, 7% to 50% of individuals with no or only mild cognitive impairment met one or more of the morphological AD criteria, while only 17% to 20% were free of considerable AD pathology [9,33,39,41].”
BackgroundDisruption of neocortical histone H3 homeostasis by soluble Aβ: implications for Alzheimer's disease
Lithner, C. U., Lacor, P. N., Zhao, W.-Q., Mustafiz, T., Klein, W. L., Sweatt, J. D., & Hernandez, C. M. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2012.12.028 · Cited by 67
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)
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
