Cited by 2,499Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsPsychological Testing and Assessment

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Diagnosis of Alzheimer's Disease

Khachaturian, Z. S.·1985·Archives of Neurology

DOI 10.1001/archneur.1985.04060100083029

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Abstract

Early and accurate diagnosis of Alzheimer's disease (AD) has a major impact on the progress of research on dementia. To address the problems involved in diagnosing AD in its earliest stages, the National Institute on Aging, the American Association of Retired Persons, the National Institute of Neurological and Communicative Disorders and Stroke, and the National Institute of Mental Health jointly sponsored a workshop for planning research. The purpose of the meeting was to identify the most important scientific research opportunities and the crucial clinical and technical issues that influence the progress of research on the diagnosis of AD. The 37 participants included some of the most knowledgeable and eminent scientists and physicians actively involved in the study of AD. The participants were divided among six panels representing the disciplines of neurochemistry, neuropathology, neuroradiology, neurology, neuropsychology, and psychiatry. Within each of the panels, participants discussed specific areas of research requiring further

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Goux, W. J., Rodriguez, S., & Sparkman, D. R. (1995) · FEBS Letters · doi:10.1016/0014-5793(95)00486-s · Cited by 26
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Hedera, P., Lerner, A., Castellani, R., & Friedland, R. (1995) · Journal of Neurological Sciences · doi:10.1016/0022-510x(94)00222-a · Cited by 30
Cholinesterases colocalize with sites of neurofibrillary degeneration in aged and Alzheimer's brains
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Age-dependent effect of Alzheimer’s risk variant of CLU on EEG alpha rhythm in non-demented adults
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A monoclonal antibody against synthetic Aβ dimer assemblies neutralizes brain‐derived synaptic plasticity‐disrupting Aβ
O’Nuallain, B., Klyubin, I. V., Donald, J. M. M., Foster, J. S., Welzel, A. T., Barry, A. E., Dykoski, R. K., Cleary, J. P., Gebbink, M. F. B. G., Rowan, M. J., et al. (2011) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2011.07389.x · Cited by 33
“Pathologically, AD is characterized by the presence of extracellular amyloid plaques, intraneuronal neurofibrillary tangles and synaptic loss throughout the limbic and association cortices (Alzheimer 1906; Kidd 1964; Khachaturian 1985; Hardy and Allsop 1991; Selkoe 1991).”
Background
Racemization of the amyloidal β Asp1 residue blocks the acceleration of fibril formation caused by racemization of the Asp23 residue
Sakai‐Kato, K., Naito, M., & Utsunomiya‐Tate, N. (2007) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2007.10.014 · Cited by 32
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Mukherjee, S., & Adams, J. D. (1997) · Molecular and Chemical Neuropathology · doi:10.1007/bf02815167 · Cited by 29
“Neuropathological confirmation of AD was performed according to a modification of a diagnostic protocol ( Khachaturian, 1985 ), as established by the Consortium to Establish a Registry in Alzheimer disease (CERAD).”
Method
Effects of freezing storage time on the density of muscarinic receptors in the human postmortem brain: an autoradiographic study in control and Alzheimer's disease brain tissues.
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“The freezing storage process used in this work is identical to that described in classical studies analysing human brain MR [3-5,15,25].”
MethodInfluential
Immunohistochemical examination of phosphorylated tau in granulovacuolar degeneration granules
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“It is not unexpected that the pathological diagnosis of AD is based on both amyloid and protein deposits [23,24].”
Background
α-Synuclein-mediated neurodegeneration in Dementia with Lewy bodies: the pathobiology of a paradox
Simon, C. A., Soga, T., Okano, H. J., & Parhar, I. S. (2021) · Cell & Bioscience · doi:10.1186/s13578-021-00709-y · Cited by 35
“, neurofibrillary tangles, neuritic plaques) that is adequate to meet the neuropathological diagnostic criteria for AD [20, 89, 90].”
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Ageing, Alzheimer disease and mental retardation
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Ragnarsson, L., Mortensen, M., Dodd, P. R., & Lewis, R. (2002) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2002.00872.x · Cited by 28
“Diagnosis of AD was based on the Khachaturian (1985) criteria as an absolute minimal quantitative standard, with the presence of neocortical neurofibrillary tangles also required.”
Method
Phosphorylation of MARCKS in Alzheimer disease brains
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Association of apolipoprotein E genotype and intronic polymorphism of the presenilin-1 gene with Alzheimer's disease in elderly Taiwan Chinese
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Proposals for Re-evaluation of Current Autopsy Criteria for the Diagnosis of Alzheimer’s Disease
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Platelet of Alzheimer patients: Increased counts and subnormal uptake and accumulation of [14C]5-hydroxytryptamine
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β‐Amyloid Protein Precursor and τ mRNA Levels Versus β‐Amyloid Plaque and Neurofibrillary Tangles in the Aged Human Brain
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“The neuropathologic hallmarks of AD include the early loss of neocortical synapses, the formation of neurofibrillary tangles (NFTs), and the presence of neuritic plaques in the hippocampus and temporal cortex [2].”
Background
Linkage to chromosome 14q in Alzheimer's disease (AD) patients without psychotic symptoms
Avramopoulos, D., Fallin, M. D., & Bassett, S. (2005) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30074 · Cited by 27
“A clinical diagnosis of AD has been confirmed at autopsy using standard criteria [Khachaturian, 1985] in 154 of the 159 (97”
Method
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Fibroblast growth factor 10 ameliorates neurodegeneration in mouse and cellular models of Alzheimer's disease via reducing tau hyperphosphorylation and neuronal apoptosis
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Microstate feature fusion for distinguishing AD from MCI
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“It cannot be cured and is most commonly seen after the age of 60 years [1, 2], but early detection can allow medication to slow its progression.”
Background
Correlation-Aware Sparse and Low-Rank Constrained Multi-Task Learning for Longitudinal Analysis of Alzheimer's Disease
Jiang, P., Wang, X., Li, Q.-L., Jin, L., & Li, S.-Y. (2019) · IEEE journal of biomedical and health informatics · doi:10.1109/jbhi.2018.2885331 · Cited by 26
Exploring the selective vulnerability in Alzheimer disease using tissue specific variant analysis
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Loss-of-function PCSK9 mutations are not associated with Alzheimer disease
Paquette, M., Saavedra, Y. G. L., Poirier, J., Théroux, L., Dea, D., Baass, A., & Dufour, R. (2018) · Journal of Geriatric Psychiatry and Neurology · doi:10.1177/0891988718764330 · Cited by 26
Effects of exposure to aluminum on long-term potentiation and AMPA receptor subunits in rats in vivo.
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Restless Legs Syndrome Risk Factors, Behaviors, and Diagnoses in Persons With Early to Moderate Dementia and Sleep Disturbance
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Phosphorylated tau in neuritic plaques of APPsw/Tauvlw transgenic mice and Alzheimer disease
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Lib, transcriptionally induced in senile plaque-associated astrocytes, promotes glial migration through extracellular matrix
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Hippocampal, but not parahippocampal, damage in a case of dense retrograde amnesia: a pathological study.
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Absence of aluminium in neurofibrillary tangles in Alzheimer's disease.
Makjanić, J., Mcdonald, B., Chen, C., & Watt, F. (1998) · Neuroscience Letters · doi:10.1016/s0304-3940(97)00940-3 · Cited by 26
Posterior cortical atrophy: Unusual feature of alzheimer's disease
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Cortical cathepsin D activity and immunolocalization in Alzheimer disease, critical coronary artery disease, and aging
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“The clinical diagnosis of AD was based on the NICDS-ADRDA work group guidelines, but the diagnosis was definitely established pathologically utilizing standard accepted criteria using multiple sections stained by the Bielschowsky method ( Khachaturian, 1985 ).”
BackgroundMethod
Cortical mapping of Alzheimer pathology in brains of aged non-demented subjects
Vermersch, P., David, J.-P., Frigard, B., Fallet‐Bianco, C., Wattez, A., Petit, H., & Delacourte, A. (1995) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/0278-5846(95)00195-6 · Cited by 26
Cerebral microvessels in Alzheimer's have reduced protein kinase C activity.
Grammas, P., Moore, P., Botchlet, T., Hanson-Painton, O., Cooper, D., Ball, M., & Roher, A. (1995) · Neurobiology of Aging · doi:10.1016/0197-4580(95)00048-j · Cited by 26
Calbindin D28k mRNA in hippocampus, superior temporal gyrus and cerebellum: comparison between control and Alzheimer disease subjects.
Maguire-Zeiss, K., Li, Z.-W., Shimodal, L. M. N., & Hamill, R. (1995) · Brain Research. Molecular Brain Research · doi:10.1016/0169-328x(95)00035-q · Cited by 26
Alzheimer's Disease and Idiopathic Parkinson's Disease Coexistence
Rajput, A., Rozdilsky, B., & Rajput, A. (1993) · Journal of Geriatric Psychiatry and Neurology · doi:10.1177/089198879300600306 · Cited by 26
Characterization of neurotransmitters and related metabolites in Daphnia magna juveniles deficient in serotonin and exposed to neuroactive chemicals that affect its behavior: A targeted LC-MS/MS method
Fuertes, I., & Barata, C. (2020) · Chemosphere · doi:10.1016/j.chemosphere.2020.127814 · Cited by 36
Significance of cytosolic cathepsin D in Alzheimer's disease pathology: Protective cellular effects of PLGA nanoparticles against β‐amyloid‐toxicity
Wang, Y., Wu, Q., Anand, B. G., Karthivashan, G., Phukan, G., Yang, J., Thinakaran, G., Westaway, D. A., & Kar, S. (2020) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12647 · Cited by 29
Role of GTPases in the Regulation of Mitochondrial Dynamics in Alzheimer’s Disease and CNS-Related Disorders
Alexiou, A. T., Soursou, G., Chatzichronis, S., Gasparatos, E., Kamal, M. A., Yarla, N. S., Perveen, A., Barreto, G. E., & Ashraf, G. M. (2018) · Molecular Neurobiology · doi:10.1007/s12035-018-1397-x · Cited by 28
Factors Determining Disease Duration in Alzheimer’s Disease: A Postmortem Study of 103 Cases Using the Kaplan-Meier Estimator and Cox Regression
Armstrong, R. A. (2014) · BioMed Research International · doi:10.1155/2014/623487 · Cited by 22
What is aging? What is its role in Alzheimer's disease? What can we do about it?
Ashford, J., Atwood, C., Blass, J., Bowen, R., Finch, C., Iqbal, K., Joseph, J., & Perry, G. (2005) · Journal of Alzheimer's Disease · doi:10.3233/jad-2005-7308 · Cited by 25
Autopsy study of Alzheimer's disease brain pathology in schizophrenia
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“The National Institute on Aging (NIA) criteria for AD (Khachaturian, 1985) used in some of the studies cited above have been reported to yield some cases of false-positive diagnosis (Mizutani, 1994).”
Method
Neuropathological Criteria for the Diagnosis of Alzheimer’s Disease: Are We Really Ready Yet?
Ball, M. J., & MURDOCH, G. H. (1997) · Neurobiology of Aging · doi:10.1016/s0197-4580(97)00074-2 · Cited by 28
“If a much worse lesional burden is needed to meet the Khachaturian criteria of an older patient (38), how can we simultaneously assume such lesions are occurring on a background of age-related decrements in physiological reserve? Yet it truly is every bit as plausible that the “simplified” (e.”
Background
Further evidence for an association between a mutation in the APP gene and Lewy body formation.
Halliday, G., Brooks, W., Arthur, H., Creasey, H., & Broe, G. (1997) · Neuroscience Letters · doi:10.1016/s0304-3940(97)00294-2 · Cited by 25
Indomethacin and nordihydroguaiaretic acid inhibition of amyloid beta protein (25-35) activation of phospholipases A2 and D of LA-N-2 cells.
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Inconstant apolipoprotein E (ApoE)-like immunoreactivity in amyloid β protein deposits: relationship with APOE genotype in aging brain and Alzheimer's disease
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Quantitation of Alzheimer's amyloid peptide and identification of related amyloid proteins by dot-blot immunoassay.
Permanne, B., Buée, L., David, J., Fallet-Bianco, C., Dimenza, C., & Delacourte, A. (1995) · Brain Research · doi:10.1016/0006-8993(95)00431-o · Cited by 25
Study of Alzheimer's Dementia Patients with Parkinsonian Features
Snowden, M., Bowen, J., Hughes, J. P., & Larson, E. (1995) · Journal of Geriatric Psychiatry and Neurology · doi:10.1177/089198879500800302 · Cited by 25
Dementia: diagnosis and emergency behavioral complications.
Tueth, M. (1995) · Journal of Emergency Medicine · doi:10.1016/0736-4679(95)80011-5 · Cited by 25
Alzheimer's Disease: The Problem of Incorrect Clinical Diagnosis
McDaniel, L. D., Lukovits, T. G., & McDaniel, K. (1993) · Journal of Geriatric Psychiatry and Neurology · doi:10.1177/089198879300600409 · Cited by 25
Vascular amyloid deposition in Alzheimer's disease. Neither necessary nor sufficient for the local formation of plaques or tangles.
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Multi-view prediction of Alzheimer’s disease progression with end-to-end integrated framework
Zhao, Y., Ma, B., Che, T., Li, Q., Zeng, D., Wang, X., & Li, S. (2021) · Journal of Biomedical Informatics · doi:10.1016/j.jbi.2021.103978 · Cited by 30
Perspective: Clinical relevance of the dichotomous classification of Alzheimer's disease biomarkers: Should there be a “gray zone”?
McRae‐McKee, K., Udeh‐Momoh, C. T., Price, G. J., Bajaj, S., de Jager, C. A., Scott, D., Hadjichrysanthou, C., McNaughton, E., Bracoud, L., Ahmadi‐Abhari, S., et al. (2019) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2019.07.010 · Cited by 26
“, in 1985, first introduced the concept that Alzheimer’s disease represents a biological construct, with key neuropathological features of increased burden of amyloid and tau, associated with evidence of neurodegeneration and brain atrophy [3].”
Background
TNF-related apoptosis-inducing ligand level in Alzheimer’s disease
Genç, Ş., Egrilmez, M., Yaka, E., Çavdar, Z., Iyilikci, L., Yener, G., & Genc, K. (2009) · Neurological Sciences · doi:10.1007/s10072-009-0047-5 · Cited by 24
Schizophrenia in Late Life: Aging Effects on Symptoms and Course of Illness
Harvey, P. D. (2004) · doi:10.1037/10873-005 · Cited by 24
Alzheimer changes are common in aged drivers killed in single car crashes and at intersections
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“NFTs are not included in CERAD criteria, but several authors consider them more reliable indicators of AD than NPs with better correlation to the degree of dementia [23–27].”
Background
Diagnostic Criteria for the Neuropathological Assessment of Alzheimer’s disease: Current Status and Major Issues
Wı́sniewski, H. M., & Silverman, W. P. (1997) · Neurobiology of Aging · doi:10.1016/s0197-4580(97)00068-7 · Cited by 22
Early-onset Alzheimer’s disease with depression as the first symptom: a case report with literature review
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“The main pathological manifestations of AD are characterized by plaques formed by extracellular amyloid (Aβ) aggregates and neurofibrillary tangles (NFTs) formed by abnormal intracellular tau protein phosphorylation aggregates (4).”
Background
Role of hippocampal subfields in neurodegenerative disease progression analyzed with a multi-scale attention-based network
Xu, H.-B., Liu, Y., Wang, L., Zeng, X., Xu, Y., & Wang, Z. (2023) · NeuroImage: Clinical · doi:10.1016/j.nicl.2023.103370 · Cited by 23
“…or functional neurodegeneration of the cerebral cortex and is characterized by memory loss, decreased learning ability and cognitive dysfunction[1], in which mild cognitive impairment (MCI) is the stage be-tween the expected cognitive decline of normal aging (i.e. Healthy Control, HC) and the…”
Vascular endothelial‐cadherin as a marker of endothelial injury in preclinical Alzheimer disease
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Dual-phase 18F-florbetaben PET provides cerebral perfusion proxy along with beta-amyloid burden in Alzheimer’s disease
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“…(A β ) plaques and intracellular neurofibrillary tangles (NFTs) in autopsied brain is still the gold standard for diagnosis of AD; however, postmortem studies have indicated that there is only a modest correspondence of autopsy results with the clinical diagnosis of AD (Khachaturian, 1985).”
Vascular protective effects of KLF2 on Aβ-induced toxicity: Implications for Alzheimer’s disease
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Vitamin A Deficiency in Rats Induces Anatomic and Metabolic Changes Comparable with Those of Neurodegenerative Disorders
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Ubiquitin immunoreactivity of paired helical filaments differs in Alzheimer’s disease and corticobasal degeneration
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Cholinergic structures and neuropathologic alterations in the olfactory bulb of Alzheimer's disease brain samples.
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Paired helical filaments in corticobasal degeneration: the fine fibrillary structure with NanoVan
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Psychiatric Illnesses in the Elderly: A Review
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Biological Markers for the Clinical Diagnosis of Alzheimer's Disease.
Arai, H. (1996) · The Tohoku Journal of Experimental Medicine · doi:10.1620/tjem.179.65 · Cited by 21
Apolipoprotein E and the neuropathology of dementia.
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A Swedish programme for dementia diagnostics in primary healthcare
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Decreased nigral neuromelanin in Alzheimer's disease
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Tau protein expression in frontotemporal dementias.
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Functional brain imaging as a looking-glass into the degraded brain: reviewing evidence from Alzheimer disease in relation to normal aging
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“The neuropathology of AD is characterized by the number of senile plaques (SP) and neuro®brillary tangles (NFT) in various brain regions, which has been used for de®nite diagnosis (Khatchaturian, 1985).”
Basal ganglia organization in amphibians: Chemoarchitecture
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Endogenous Alzheimer's brain factor and oxidized glutathione inhibit antagonist binding to the muscarinic receptor.
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Differential expression of exons 10 and 11 in normal tau and tau associated with paired helical filaments
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Human neurons that constitutively secrete A beta do not induce Alzheimer's disease pathology following transplantation and long-term survival in the rodent brain.
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Background
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Background
Design, Synthesis and Bioassays of 3‐Substituted‐3‐Hydroxyoxindoles for Cholinesterase Inhibition
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Alzheimer's Disease Neuropathology: Current Status of Interpretation of Lesion Developmenta
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Role of tau versus TDP‐43 pathology on medial temporal lobe atrophy in aging and Alzheimer's disease
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“…& milestones: Blue: Mid-80s—identification of A β & tau as core proteins in plaques and tangles 170–174 ; 1985—Khachaturian criteria of AD pathology 175 ; 1991—Braak staging of neurofibrillary tangles 16 ; 1991—CERAD criteria 176 ; 1997—NIA-R criteria for the neuropathological diagnosis of AD 177…”
Dementia analysis from functional connectivity network with graph neural networks
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Human Plasma Protein Corona of Aβ Amyloid and Its Impact on Islet Amyloid Polypeptide Cross-Seeding
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Authors: Khachaturian, Z. S.
Corresponding author: Khachaturian, Z. S.
Venue: Archives of Neurology
Publisher: American Medical Association (AMA)
Published: 1985-11-01
Volume: 42
Issue: 11
Pages: 1097-1105
ISSN: 0003-9942 (ISSN-L)
DOI: 10.1001/archneur.1985.04060100083029
OpenAlex: W2171405125
Cited by: 2,499
References: 10
Citations by year: 2026: 10 · 2025: 27 · 2024: 26 · 2023: 31 · 2022: 38 · 2021: 46 · 2020: 43 · 2019: 35 · 2018: 29 · 2017: 27 · 2016: 36 · 2015: 27 · 2014: 41 · 2013: 34 · 2012: 41
FWCI: 40.91
Type: journal article
Language: en
Open access: closed
Locations: Archives of Neurology (publishedVersion)
PubMed (publishedVersion)
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
Social Sciences › Psychology › Applied Psychology › Psychological Testing and Assessment
Keywords: Alzheimer's disease, early diagnosis, dementia, neurochemistry, neuropathology, neuroradiology, neuropsychology
MeSH terms: Alzheimer Disease, Humans

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