The DOI matches its Crossref record; 298 of the 298 references it cites were found in a registry or an index.
Preclinical Alzheimer’s Disease: Definition, Natural History, and Diagnostic Criteria
Open accessAbstract
During the past decade, a conceptual shift occurred in the field of Alzheimer's disease (AD) considering the disease as a continuum. Thanks to evolving biomarker research and substantial discoveries, it is now possible to identify the disease even at the preclinical stage before the occurrence of the first clinical symptoms. This preclinical stage of AD has become a major research focus as the field postulates that early intervention may offer the best chance of therapeutic success. To date, very little evidence is established on this “silent” stage of the disease. A clarification is needed about the definitions and lexicon, the limits, the natural history, the markers of progression, and the ethical consequence of detecting the disease at this asymptomatic stage. This article is aimed at addressing all the different issues by providing for each of them an updated review of the literature and evidence, with practical recommendations.
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“This could explain why part of the risk factors for cardiovascular disease are in common with AD, including hypertension, dyslipidemia, diabetes, obesity, dietary factors, smoking, and physical activity (Figure 1B).”
From Alzheimer's Disease: Treatment Strategies and Their Limitations. (2022) · cites this paper as [22]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Thus, lifestyle is also an important risk factor, where intellectual, physical, and social activities, as well as diet, may help to prevent AD [1,22,100,101,102,103].”
From Alzheimer's Disease: Treatment Strategies and Their Limitations. (2022) · cites this paper as [22]
The cited source says what the claim attributes to it.
In the citing paper
“Thus, the disease is now regarded as a continuum rather than three distinct clinically defined entities [15].”
From NIA‐AA Research Framework: Toward a biological definition of Alzheimer's disease (2018) · cites this paper as [15]
The cited source says what the claim attributes to it.
In the citing paper
“While differences remain, IWG 2016 and the NIA research framework are aligned on the key issue that the combination of an abnormal Aβ and tau biomarker constitutes AD regardless of cognitive symptoms, and thus AD is a biologically defined entity throughout its continuum.”
From NIA‐AA Research Framework: Toward a biological definition of Alzheimer's disease (2018) · cites this paper as [15]
In the citing paper
“Furthermore, drug development research for AD has become more complicated as preclinical and prodromal AD populations are potentially included in current trials, as well as traditionally included populations of all the clinical stages of AD dementia.38”
From Current and Future Treatments in Alzheimer Disease: An Update (2020) · cites this paper as [38]
In the citing paper
“Although the use of clinical trial simulators is not frequent in recent research,38”
From Current and Future Treatments in Alzheimer Disease: An Update (2020) · cites this paper as [38]
In the citing paper
“This asymptomatic phase of AD (AsymAD) is currently considered a preclinical stage of the disease [27, 28].”
From Deep proteomic network analysis of Alzheimer’s disease brain reveals alterations in RNA binding proteins and RNA splicing associated with disease (2018) · cites this paper as [27]
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
Neuropathological stageing of Alzheimer-related changes.
Braak, H., & Braak, E. (1991) · Acta Neuropathologica · doi:10.1007/bf00308809 · Cited by 16,123 · cited 1×
“From the tau protein perspective, one study showed that alterations in CSF levels of p-tau may precede those of Ab [57], which correlates with postmortem evidence showing the presence of neurofibrillary tangles in the entorhinal cortex and in hippocampal-related structures [58,59] as the first neuropathologic event in…”
ResultCorder, E. H., Saunders, A. M., Strittmatter, W. J., Schmechel, D. E., Gaskell, P. C., Small, G. W., Roses, A. D., Haines, J. L., & Pericak-Vance, M. A. (1993) · Science · doi:10.1126/science.8346443 · Cited by 9,429
Sperling, R. A., Aisen, P. S., Beckett, L. A., Bennett, D. A., Craft, S., Fagan, A. M., Iwatsubo, T., Jack, C. R., Kaye, J., Montine, T. J., et al. (2011) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2011.03.003 · Cited by 7,155
Self-citationBiomarkers and surrogate endpoints: Preferred definitions and conceptual framework
Biomarkers Definitions Working Group (2001) · Clinical Pharmacology & Therapeutics · doi:10.1067/mcp.2001.113989 · Cited by 6,771
Mirra, S. S., Heyman, A., McKeel, D., Sumi, S. M., Crain, B. J., Brownlee, L. M., Vogel, F. S., Hughes, J. P., Belle, G. V., Berg, L., et al. (1991) · Neurology · doi:10.1212/wnl.41.4.479 · Cited by 4,961
Exercise training increases size of hippocampus and improves memory
Erickson, K. I., Voss, M. W., Prakash, R. S., Basak, C., Szabo, A., Chaddock, L., Kim, J. S., Heo, S., Alves, H., White, S. M., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1015950108 · Cited by 4,855
Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade
Jack, C. R., Knopman, D. S., Jagust, W. J., Shaw, L. M., Aisen, P. S., Weiner, M. W., Petersen, R. C., & Trojanowski, J. Q. (2010) · The Lancet Neurology · doi:10.1016/s1474-4422(09)70299-6 · Cited by 4,806
Self-citationJack, C. R., Knopman, D. S., Jagust, W. J., Petersen, R. C., Weiner, M. W., Aisen, P. S., Shaw, L. M., Vemuri, P., Wiste, H. J., Weigand, S. D., et al. (2013) · The Lancet Neurology · doi:10.1016/s1474-4422(12)70291-0 · Cited by 4,396
Self-citationMeta-Analysis of 74,046 Individuals Identifies 11 New Susceptibility Loci for Alzheimer’s Disease
(EADI), E. A. D. I., Lambert, J.-C., (GERAD), G. A. E. R. I. A. D., Alzheimer's Disease Genetic Consortium (ADGC), (CHARGE), C. F. H. A. A. R. I. G. E., Ibrahim-Verbaas, C. A., Harold, D., Naj, A. C., Sims, R., Bellenguez, C., et al. (2013) · Nature Genetics · doi:10.1038/ng.2802 · Cited by 4,336
Self-citationClinical and biomarker changes in dominantly inherited Alzheimer's disease
Bateman, R. J., Xiong, C., Benzinger, T. L. S., Fagan, A. M., Goate, A., Fox, N. C., Marcus, D. S., Cairns, N. J., Xie, X., Blazey, T. M., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1202753 · Cited by 3,814
Self-citation
Cited by
Sorted by citations
NIA‐AA Research Framework: Toward a biological definition of Alzheimer's disease
Jack, C. R., Bennett, D. A., Blennow, K., Carrillo, M. C., Dunn, B., Haeberlein, S. B., Holtzman, D. M., Jagust, W., Jessen, F., Karlawish, J., et al. (2018) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2018.02.018 · Cited by 10,537
“Preclinical AD in IWG 2016 [15] defines a CU individual with an abnormal Ab biomarker and normal tau (A1T2) as “at risk for AD, asymptomatic A1” and one with A2T1 as “at risk for AD, asymptomatic T1”.”
Self-citationDementia prevention, intervention, and care
Livingston, G., Sommerlad, A., Orgeta, V., Costafreda, S. G., Huntley, J., Ames, D., Ballard, C., Banerjee, S., Burns, A., Cohen-Mansfield, J., et al. (2017) · The Lancet · doi:10.1016/s0140-6736(17)31363-6 · Cited by 6,072
Self-citationComprehensive Review on Alzheimer’s Disease: Causes and Treatment
Breijyeh, Z., & Karaman, R. (2020) · Molecules · doi:10.3390/molecules25245789 · Cited by 2,789
Lane, C. A., Hardy, J., & Schott, J. M. (2018) · European Journal of Neurology · doi:10.1111/ene.13439 · Cited by 2,616
The characterisation of subjective cognitive decline
Jessen, F., Amariglio, R. E., Buckley, R. F., van der Flier, W. M., Han, Y., Molinuevo, J. L., Rabin, L., Rentz, D. M., Rodriguez-Gomez, O., Saykin, A. J., et al. (2020) · The Lancet Neurology · doi:10.1016/s1474-4422(19)30368-0 · Cited by 1,389
Self-citationAgeing, neurodegeneration and brain rejuvenation
Wyss-Coray, T. (2016) · Nature · doi:10.1038/nature20411 · Cited by 1,147
Clinical diagnosis of Alzheimer’s disease: Recommendations of the International Working Group
Dubois, B., Villain, N., Frisoni, G. B., Rabinovici, G. D., Sabbagh, M., Cappa, S., Bejanin, A., Bombois, S., Epelbaum, S., Teichmann, M., et al. (2021) · The Lancet Neurology · doi:10.1016/s1474-4422(21)00066-1 · Cited by 1,051
Self-citationCurrent and Future Treatments in Alzheimer Disease: An Update
Yiannopoulou, K. G., & Papageorgiou, S. G. (2020) · Journal of Central Nervous System Disease · doi:10.1177/1179573520907397 · Cited by 966
Lecanemab: Appropriate Use Recommendations
Cummings, J., Apostolova, L., Rabinovici, G. D., Atri, A., Aisen, P., Greenberg, S., Hendrix, S., Selkoe, D., Weiner, M., Petersen, R. C., et al. (2023) · The Journal of Prevention of Alzheimer's Disease · doi:10.14283/jpad.2023.30 · Cited by 961
Self-citationGlobal estimates on the number of persons across the Alzheimer's disease continuum
Gustavsson, A., Norton, N., Fast, T., Frölich, L., Georges, J., Holzapfel, D., Kirabali, T., Krolak‐Salmon, P., Rossini, P. M., Ferretti, M. T., et al. (2023) · Alzheimer's & Dementia · doi:10.1002/alz.12694 · Cited by 895
Understanding the impact of sex and gender in Alzheimer’s disease: A call to action
Nebel, R. A., Aggarwal, N. T., Barnes, L. L., Gallagher, A., Goldstein, J. M., Kantarci, K., Mallampalli, M. P., Mormino, E. C., Scott, L., Yu, W. H., et al. (2018) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2018.04.008 · Cited by 839
Alzheimer's disease drug development pipeline: 2019
Cummings, J., Lee, G., Ritter, A., Sabbagh, M., & Zhong, K. (2019) · Alzheimer's & Dementia: Translational Research & Clinical Interventions · doi:10.1016/j.trci.2019.05.008 · Cited by 762
Self-citationDiagnosis of Early Alzheimer's Disease: Clinical Practice in 2021
Porsteinsson, A. P., Isaacson, R. S., Knox, S., Sabbagh, M. N., & Rubino, I. (2021) · The Journal of Prevention of Alzheimer's Disease · doi:10.14283/jpad.2021.23 · Cited by 744
Alzheimer’s disease prevention: from risk factors to early intervention
Crous‐Bou, M., Minguillón, C., Gramunt, N., & Molinuevo, J. L. (2017) · Alzheimer s Research & Therapy · doi:10.1186/s13195-017-0297-z · Cited by 730
Self-citationGale, S. A., Acar, D., & Daffner, K. R. (2018) · The American Journal of Medicine · doi:10.1016/j.amjmed.2018.01.022 · Cited by 788
Strategic roadmap for an early diagnosis of Alzheimer's disease based on biomarkers
Frisoni, G. B., Boccardi, M., Barkhof, F., Blennow, K., Cappa, S., Chiotis, K., Démonet, J.-F., Garibotto, V., Giannakopoulos, P., Gietl, A., et al. (2017) · The Lancet Neurology · doi:10.1016/s1474-4422(17)30159-x · Cited by 626
Self-citationAlzheimer's Disease: Treatment Strategies and Their Limitations.
Passeri, E., Elkhoury, K., Morsink, M., Broersen, K., Linder, M., Tamayol, A., Malaplate, C., Yen, F. T., & Arab-Tehrany, E. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232213954 · Cited by 689
“Indeed, the new diagnostic criteria require the use of cerebrospinal fluid (CSF) biomarkers, including total and hyperphosphorylated Tau protein as well as Aβ42 or Aβ42/Aβ40 ratio and positron emission tomography (PET) of τau and amyloid to attribute a probability (high, medium, or low) of the underlying AD-related ne…”
BackgroundMethodInfluentialOn the path to 2025: understanding the Alzheimer’s disease continuum
Aisen, P. S., Cummings, J., Jack, C. R., Morris, J. C., Sperling, R., Frölich, L., Jones, R. W., Dowsett, S. A., Matthews, B. R., Raskin, J., et al. (2017) · Alzheimer's Research & Therapy · doi:10.1186/s13195-017-0283-5 · Cited by 556
Self-citationBabulal, G. M., Quiroz, Y. T., Albensi, B. C., Arenaza‐Urquijo, E., Astell, A. J., Babiloni, C., Bahar‐Fuchs, A., Bell, J., Bowman, G. L., Brickman, A. M., et al. (2019) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2018.09.009 · Cited by 528
Self-citationAlzheimer’s disease: Recent treatment strategies
Vaz, M., & Silvestre, S. (2020) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2020.173554 · Cited by 547
Propagation and spread of pathogenic protein assemblies in neurodegenerative diseases
Jucker, M., & Walker, L. C. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0238-6 · Cited by 450
Current understanding of metal ions in the pathogenesis of Alzheimer’s disease
Wang, L., Yin, Y.-L., Liu, X.-Z., Shen, P., Zheng, Y.-G., Lan, X.-R., Lu, C.-B., & Wang, J.-Z. (2020) · Translational Neurodegeneration · doi:10.1186/s40035-020-00189-z · Cited by 454
Imaging tau and amyloid-β proteinopathies in Alzheimer disease and other conditions
Villemagne, V. L., Doré, V., Burnham, S. C., Masters, C. L., & Rowe, C. C. (2018) · Nature Reviews Neurology · doi:10.1038/nrneurol.2018.9 · Cited by 447
Self-citationSuárez‐Calvet, M., Karikari, T. K., Ashton, N. J., Lantero Rodríguez, J., Milà‐Alomà, M., Gispert, J. D., Salvadó, G., Minguillon, C., Fauria, K., Shekari, M., et al. (2020) · EMBO Molecular Medicine · doi:10.15252/emmm.202012921 · Cited by 401
Self-citationCognitive Reserve and the Prevention of Dementia: the Role of Physical and Cognitive Activities
Cheng, S.-T. (2016) · Current Psychiatry Reports · doi:10.1007/s11920-016-0721-2 · Cited by 385
Systematic Review on Resting-State EEG for Alzheimer’s Disease Diagnosis and Progression Assessment
Cassani, R., Estarellas, M., San-Martin, R., Fraga, F. J., & Falk, T. H. (2018) · Disease Markers · doi:10.1155/2018/5174815 · Cited by 415
α-synuclein in the pathophysiology of Alzheimer’s disease
Twohig, D., & Nielsen, H. M. (2019) · Molecular Neurodegeneration · doi:10.1186/s13024-019-0320-x · Cited by 374
Koch, G., Bonnı̀, S., Pellicciari, M. C., Casula, E. P., Mancini, M., Esposito, R., Ponzo, V., Picazio, S., Lorenzo, F. D., Serra, L., et al. (2017) · NeuroImage · doi:10.1016/j.neuroimage.2017.12.048 · Cited by 369
Higginbotham, L., Ping, L., Dammer, E. B., Duong, D. M., Zhou, M., Gearing, M., Hurst, C., Glass, J. D., Factor, S. A., Johnson, E. C. B., et al. (2020) · Science Advances · doi:10.1126/sciadv.aaz9360 · Cited by 367
Higginbotham, L., Ping, L., Dammer, E. B., Duong, D. M., Zhou, M., Gearing, M., Johnson, E. C. B., Hajjar, I., Lah, J. J., Levey, A. I., et al. (2019) · doi:10.1101/806752 · Cited by 367
Role of estrogen receptors in health and disease
Chen, P., Li, B., & Ou-Yang, L. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.839005 · Cited by 339
Monteiro, A. R., Barbosa, D. J., Remião, F., & Silva, R. V. D. S. (2023) · Biochemical Pharmacology · doi:10.1016/j.bcp.2023.115522 · Cited by 375
Jack, C. R., Wiste, H. J., Weigand, S. D., Therneau, T. M., Knopman, D. S., Lowe, V., Vemuri, P., Mielke, M. M., Roberts, R. O., Machulda, M. M., et al. (2017) · The Lancet Neurology · doi:10.1016/s1474-4422(17)30077-7 · Cited by 333
Self-citationLiss, J. L., Seleri Assunção, S., Cummings, J., Atri, A., Geldmacher, D. S., Candela, S. F., Devanand, D. P., Fillit, H. M., Susman, J., Mintzer, J., et al. (2021) · Journal of Internal Medicine · doi:10.1111/joim.13244 · Cited by 312
Self-citationYiannopoulou, K. G., Anastasiou, A. I., Zachariou, V., & Pelidou, S.-H. (2019) · Biomedicines · doi:10.3390/biomedicines7040097 · Cited by 330
Plasma Amyloid as Prescreener for the Earliest Alzheimer Pathological Changes
Verberk, I. M. W., Slot, R. E., Verfaillie, S. C. J., Heijst, H., Prins, N. D., van Berckel, B. N. M., Scheltens, P., Teunissen, C. E., & van der Flier, W. M. (2018) · Annals of Neurology · doi:10.1002/ana.25334 · Cited by 315
Self-citationCerebrospinal fluid tau, neurogranin, and neurofilament light in Alzheimer's disease
Mattsson, N., Insel, P. S., Palmqvist, S., Portelius, E., Zetterberg, H., Weiner, M. W., Blennow, K., Hansson, O., & Initiative, T. A. D. N. (2016) · EMBO Molecular Medicine · doi:10.15252/emmm.201606540 · Cited by 301
Self-citationvan Oostveen, W. M., & de Lange, E. C. M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22042110 · Cited by 297
Monoaminergic neuropathology in Alzheimer’s disease
Šimić, G., Leko, M. B., Wray, S., Harrington, C. R., Delalle, I., Milošević, N. J., Bažadona, D., Buée, L., de Silva, R., Giovanni, G. D., et al. (2016) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2016.04.001 · Cited by 297
The impact of amyloid‐beta and tau on prospective cognitive decline in older individuals
Sperling, R. A., Mormino, E. C., Schultz, A. P., Betensky, R. A., Papp, K. V., Amariglio, R. E., Hanseeuw, B. J., Buckley, R., Chhatwal, J., Hedden, T., et al. (2019) · Annals of Neurology · doi:10.1002/ana.25395 · Cited by 286
Self-citationDubois, B., von Arnim, C. A. F., Burnie, N., Bozeat, S., & Cummings, J. (2023) · Alzheimer's Research & Therapy · doi:10.1186/s13195-023-01314-6 · Cited by 288
Self-citationTau PET imaging: present and future directions
Saint‐Aubert, L., Lemoine, L., Chiotis, K., Leuzy, A., Rodriguez‐Vieitez, E., & Nordberg, A. K. (2017) · Molecular Neurodegeneration · doi:10.1186/s13024-017-0162-3 · Cited by 300
Donovan, N. J., Locascio, J. J., Marshall, G. A., Gatchel, J., Hanseeuw, B. J., Rentz, D. M., Johnson, K. A., Sperling, R. A., & Study, F. T. H. A. B. (2018) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2017.17040442 · Cited by 272
Self-citationNeuroimaging advances regarding subjective cognitive decline in preclinical Alzheimer's disease
Wang, X., Huang, W., Su, L., Xing, Y., Jessen, F., Sun, Y., Shu, N., & Han, Y. (2020) · Molecular Neurodegeneration · doi:10.1186/s13024-020-00395-3 · Cited by 265
Molecular Pathogenesis of the Tauopathies
Götz, J., Halliday, G., & Nisbet, R. M. (2019) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathmechdis-012418-012936 · Cited by 276
The human connectome in Alzheimer disease — relationship to biomarkers and genetics
Yu, M., Sporns, O., & Saykin, A. J. (2021) · Nature Reviews Neurology · doi:10.1038/s41582-021-00529-1 · Cited by 265
Elahi, F. M., Casaletto, K. B., Joie, R. L., Walters, S. M., Harvey, D. J., Wolf, A. A., Edwards, L., Contreras, W. R., Karydas, A., Cobigo, Y., et al. (2019) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2019.09.004 · Cited by 258
Self-citationEntorhinal cortex dysfunction in Alzheimer's disease
Igarashi, K. M. (2022) · Trends in Neurosciences · doi:10.1016/j.tins.2022.11.006 · Cited by 276
Blood neuro‐exosomal synaptic proteins predict Alzheimer's disease at the asymptomatic stage
Jia, L., Zhu, M., Kong, C., Pang, Y., Zhang, H., Qiu, Q., Wei, C., Tang, Y., Wang, Q., Li, Y., et al. (2020) · Alzheimer s & Dementia · doi:10.1002/alz.12166 · Cited by 247
Dubois, B., Epelbaum, S., Nyasse, F., Bakardjian, H., Gagliardi, G. P., Uspenskaya, O., Houot, M., Lista, S., Cacciamani, F., Potier, M., et al. (2018) · The Lancet Neurology · doi:10.1016/s1474-4422(18)30029-2 · Cited by 253
Self-citationManagement of mild cognitive impairment (MCI): The need for national and international guidelines
Kasper, S. F., Bancher, C., Eckert, A., Förstl, H., Frölich, L., Hort, J., Korczyn, A. D., Kressig, R. W., Levin, O. S., & Palomo, M. S. M. (2020) · The World Journal of Biological Psychiatry · doi:10.1080/15622975.2019.1696473 · Cited by 252
Rossini, P. M., Iorio, R. D., Vecchio, F., Anfossi, M., Babiloni, C., Bozzali, M., Bruni, A. C., Cappa, S. F., Escudero, J., Fraga, F. J., et al. (2020) · Clinical Neurophysiology · doi:10.1016/j.clinph.2020.03.003 · Cited by 257
Self-citationNeuronal cell death mechanisms in Alzheimer’s disease: An insight
Goel, P., Chakrabarti, S., Goel, K., Bhutani, K., Chopra, T., & Bali, S. (2022) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2022.937133 · Cited by 248
Roberts, R. O., Aakre, J. A., Kremers, W. K., Vassilaki, M., Knopman, D. S., Mielke, M. M., Alhurani, R., Geda, Y. E., Machulda, M. M., Coloma, P., et al. (2018) · JAMA Neurology · doi:10.1001/jamaneurol.2018.0629 · Cited by 223
Self-citationRabin, J. S., Schultz, A. P., Hedden, T., Viswanathan, A., Marshall, G. A., Kilpatrick, E., Klein, H., Buckley, R. F., Yang, H.-S., Properzi, M., et al. (2018) · JAMA Neurology · doi:10.1001/jamaneurol.2018.1123 · Cited by 221
Self-citationJohnson, E. C. B., Dammer, E. B., Duong, D. M., Yin, L., Thambisetty, M., Troncoso, J. C., Lah, J. J., Levey, A. I., & Seyfried, N. T. (2018) · Molecular Neurodegeneration · doi:10.1186/s13024-018-0282-4 · Cited by 225
“This asymptomatic phase of AD (AsymAD) is currently considered a preclinical stage of the disease [27, 28].”
BackgroundMild Cognitive Impairment: the Manchester consensus
Dunne, R. A., Aarsland, D., O'Brien, J. T., Ballard, C. G., Banerjee, S., Fox, N. C., Isaacs, J. D., Underwood, B. R., Perry, R. J., Chan, D., et al. (2020) · Age and Ageing · doi:10.1093/ageing/afaa228 · Cited by 240
Morris, G. P., Clark, I. A., & Vissel, B. (2018) · Acta Neuropathologica · doi:10.1007/s00401-018-1918-8 · Cited by 212
El-Hayek, Y. H., Wiley, R. E., Khoury, C. P., Daya, R. P., Ballard, C., Evans, A. R., Karran, M., Molinuevo, J. L., Norton, M., & Atri, A. (2019) · Journal of Alzheimer's Disease · doi:10.3233/jad-190426 · Cited by 216
Self-citationSafiri, S., Jolfayi, A. G., Fazlollahi, A., Morsali, S., Sarkesh, A., Sorkhabi, A. D., Golabi, B., Aletaha, R., Asghari, K. M., Hamidi, S., et al. (2024) · Frontiers in Medicine · doi:10.3389/fmed.2024.1474043 · Cited by 273
Lifespan Changes of the Human Brain In Alzheimer’s Disease
Coupé, P., Manjón, J. V., Lanuza, E., & Catheline, G. (2019) · Scientific Reports · doi:10.1038/s41598-019-39809-8 · Cited by 226
Parra, M. A., Báez, S., Allegri, R., Nitríni, R., Lopera, F. J., Slachevsky, A., Custodio, N., Lira, D., Piguet, O., Kumfor, F., et al. (2018) · Neurology · doi:10.1212/wnl.0000000000004897 · Cited by 217
Gut microbiota in patients with Alzheimer’s disease spectrum: a systematic review and meta-analysis
Hung, C.-C., Chang, C., Huang, C.-W., Nouchi, R., & Cheng, C. (2022) · Aging · doi:10.18632/aging.203826 · Cited by 220
Nobili, F. M., Arbizu, J., Bouwman, F. H., Drzezga, A. E., Agosta, F., Nestor, P. J., Walker, Z., Boccardi, M., & the EANM‐EAN Task Force for the Prescription of FDG‐PET for Dementing Neurodegenerative Disorders (2018) · European Journal of Neurology · doi:10.1111/ene.13728 · Cited by 220
A Close Look at BACE1 Inhibitors for Alzheimer’s Disease Treatment
Das, B., & Yan, R. (2019) · CNS Drugs · doi:10.1007/s40263-019-00613-7 · Cited by 218
Baker, J. E., Lim, Y. Y., Pietrzak, R. H., Hassenstab, J. J., Snyder, P. J., Masters, C. L., & Maruff, P. T. (2016) · Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring · doi:10.1016/j.dadm.2016.09.002 · Cited by 214
Causes and Patterns of Dementia: An Update in the Era of Redefining Alzheimer's Disease
James, B. D., & Bennett, D. A. (2019) · Annual Review of Public Health · doi:10.1146/annurev-publhealth-040218-043758 · Cited by 213
Challenges for Alzheimer's Disease Therapy: Insights from Novel Mechanisms Beyond Memory Defects
Frozza, R. L., Lourenco, M. V., & Felice, F. G. D. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00037 · Cited by 213
Designing the next-generation clinical care pathway for Alzheimer’s disease
Hampel, H., Au, R., Mattke, S., van der Flier, W. M., Aisen, P., Apostolova, L., Chen, C., Cho, M., De Santi, S., Gao, P., et al. (2022) · Nature Aging · doi:10.1038/s43587-022-00269-x · Cited by 191
Self-citationDirect and indirect cost of managing alzheimer’s disease and related dementias in the United States
Deb, A., Thornton, J. D., Sambamoorthi, U., & Innes, K. E. (2017) · Expert Review of Pharmacoeconomics & Outcomes Research · doi:10.1080/14737167.2017.1313118 · Cited by 197
Parnetti, L., Chipi, E., Salvadori, N., D’Andrea, K., & Eusebi, P. (2019) · Alzheimer s Research & Therapy · doi:10.1186/s13195-018-0459-7 · Cited by 206
Luca, M., Di Mauro, M., Di Mauro, M., & Luca, A. (2019) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2019/4730539 · Cited by 190
Snyder, B., Shell, B., Cunningham, J. T., & Cunningham, R. L. (2017) · Physiological Reports · doi:10.14814/phy2.13258 · Cited by 190
Retinal imaging in Alzheimer's and neurodegenerative diseases
Snyder, P. J., Alber, J., Alt, C., Bain, L. J., Bouma, B. E., Bouwman, F. H., DeBuc, D. C., Campbell, M. C. W., Carrillo, M. C., Chew, E. Y., et al. (2020) · Alzheimer s & Dementia · doi:10.1002/alz.12179 · Cited by 197
Self-citationCognitive Impairment in Older Adults
Palmer, N. P., Ortega, B. T., & Joshi, P. (2022) · Psychiatric Clinics of North America · doi:10.1016/j.psc.2022.07.010 · Cited by 200
Perrotin, A., La Joie, R., de La Sayette, V., Barré, L., Mézenge, F., Mutlu, J., Guilloteau, D., Egret, S., Eustache, F., & Chételat, G. (2017) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2016.08.011 · Cited by 179
Revolution of Alzheimer Precision Neurology. Passageway of Systems Biology and Neurophysiology
Hampel, H. J., (APMI), F. T. A. P. M. I., Toschi, N., Babiloni, C., Baldacci, F., Black, K. L., Bokde, A. L. W., Bun, R. S., Cacciola, F., Cavedo, E., et al. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-179932 · Cited by 184
Self-citationAmyloid and tau imaging biomarkers explain cognitive decline from late middle-age
Betthauser, T. J., Koscik, R. L., Jonaitis, E. M., Allison, S. L., Cody, K. A., Erickson, C. M., Rowley, H. A., Stone, C. K., Mueller, K. D., Clark, L. R., et al. (2019) · Brain · doi:10.1093/brain/awz378 · Cited by 176
Astrocytes in Alzheimer's disease: pathological significance and molecular pathways
Preman, P., Alfonso-Triguero, M., Alberdi, E., Verkhratsky, A., & Arranz, A. M. (2021) · Cells · doi:10.3390/cells10030540 · Cited by 176
Barone, E., Domenico, F. D., Marzia Perluigi, A., & Butterfield, D. A. (2021) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2021.09.006 · Cited by 182
Alzheimer's Disease Puzzle: Delving into Pathogenesis Hypotheses
(2024) · aging and disease · doi:10.14336/ad.2023.0608 · Cited by 183
Boespflug, E. L., & Iliff, J. J. (2017) · Biological Psychiatry · doi:10.1016/j.biopsych.2017.11.031 · Cited by 179
Rabinovici, G. D. (2019) · Continuum · doi:10.1212/con.0000000000000700 · Cited by 170
Self-citationPast, present and future role of retinal imaging in neurodegenerative disease
Kashani, A. H., Asanad, S., Chan, J. W., Singer, M., Zhang, J., Sharifi, M., Khansari, M. M., Abdolahi, F., Shi, Y., Biffi, A., et al. (2021) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2020.100938 · Cited by 169
Molecular Mechanisms of Neuroinflammation in Aging and Alzheimer’s Disease Progression
Andronie-Cioară, F. L., Ardelean, A. I., Nistor-Cseppento, C. D., Jurcău, A., Jurcău, M. C., Pașcalău, N., & Marcu, F. M. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24031869 · Cited by 170
Differential diagnosis of Alzheimer’s disease using spectrochemical analysis of blood
Paraskevaidi, M., Morais, C. L. M., Lima, K. M. G., Snowden, J. S., Saxon, J. A., Richardson, A. M. T., Jones, M. S., Mann, D. M. A., Allsop, D., Martin‐Hirsch, P. L., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1701517114 · Cited by 163
Yu, M., Engels, M. M. A., Hillebrand, A., van Straaten, E. C. W., Gouw, A. A., Teunissen, C. E., van der Flier, W. M., Scheltens, P., & Stam, C. J. (2017) · Brain · doi:10.1093/brain/awx050 · Cited by 165
Self-citationBustamante-Barrientos, F. A., Méndez-Ruette, M., Ortloff, A., Luz‐Crawford, P., Rivera, F. J., Figueroa, C. D., Molina, L., & Bátiz, L. F. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.636176 · Cited by 180
Progression of Early Subclinical Atherosclerosis (PESA) Study
Ibáñez, B., Fernández‐Ortíz, A., Fernández‐Friera, L., García‐Lunar, I., Andrés, V., & Fuster, V. (2021) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2021.05.011 · Cited by 171
Cosín‐Tomás, M., Antonell, A., Lladó, A., Alcolea, D. A., Fortea, J., Ezquerra, M., Lleó, A., Martı́, M. J., Pallàs, M., Sánchez‐Valle, R., et al. (2016) · Molecular Neurobiology · doi:10.1007/s12035-016-0088-8 · Cited by 161
Self-citationEarly diagnosis of mild cognitive impairment and Alzheimer's disease based on salivary lactoferrin
Carro, E., Bartolomé, F. B., Bermejo‐Pareja, F., Villarejo‐Galende, A., Molina, J. A., Ortiz-Romero, P. L., Calero, M., Rábano, A., Cantero, J. L., & Orive, G. (2017) · Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring · doi:10.1016/j.dadm.2017.04.002 · Cited by 162
Passive immunotherapies targeting Aβ and tau in Alzheimer's disease
Plotkin, S. S., & Cashman, N. R. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.105010 · Cited by 161
A deep learning framework for early diagnosis of Alzheimer’s disease on MRI images
Arafa, D. A., Moustafa, H. E.-D., Ali, H. A., Eldin, A. A., & Saraya, S. F. (2023) · Multimedia Tools and Applications · doi:10.1007/s11042-023-15738-7 · Cited by 156
Electromagnetic signatures of the preclinical and prodromal stages of Alzheimer’s disease
Nakamura, A., Cuesta, P., Fernández, A., Arahata, Y., Iwata, K., Kuratsubo, I., Bundo, M., Hattori, H., Sakurai, T., Fukuda, K., et al. (2018) · Brain · doi:10.1093/brain/awy044 · Cited by 151
Dementia in Latin America: Paving the way toward a regional action plan
Parra, M. A., Báez, S., Sedeño, L., Campo, C. G., Santamaría‐García, H. A., Aprahamian, I., Bertolucci, P. H. F., Bustin, J., Bicalho, M. A. C., Cano, C. A., et al. (2020) · Alzheimer s & Dementia · doi:10.1002/alz.12202 · Cited by 155
Reactive astrogliosis: A friend or foe in the pathogenesis of Alzheimer’s disease
Kumar, A., Fontana, I. C., & Nordberg, A. (2023) · Journal of Neurochemistry · doi:10.1111/jnc.15565 · Cited by 150
Sleep disturbances and dementia risk: a multicenter study
Sindi, S., Kåreholt, I., Johansson, L., Skoog, J., Sjöberg, L., Wang, H., Johansson, B., Fratiglioni, L., Soininen, H., Solomon, A., et al. (2018) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2018.05.012 · Cited by 144
Self-citationHampel, H., O’Bryant, S. E., Durrleman, S., Younesi, E., Rojkova, K., Escott-Price, V., Corvol, J.-C., Broich, K., Dubois, B., Lista, S., et al. (2017) · Climacteric · doi:10.1080/13697137.2017.1287866 · Cited by 147
Self-citationNagaraj, S., Laskowska-Kaszub, K., Dębski, K. J., Wojsiat, J., Dąbrowski, M., Gabryelewicz, T., Kuźnicki, J., & Wojda, U. (2017) · Oncotarget · doi:10.18632/oncotarget.15109 · Cited by 148
Exercise suppresses neuroinflammation for alleviating Alzheimer’s disease
Wang, M., Zhang, H., Liang, J., Huang, J., & Chen, N. (2023) · Journal of Neuroinflammation · doi:10.1186/s12974-023-02753-6 · Cited by 154
Metadata
- Authors
- Dubois, B., Hampel, H., Feldman, H. H., Scheltens, P., Aisen, P., Andrieu, S., Bakardjian, H., Benali, H., Bertram, L., Blennow, K., Broich, K., Cavedo, E., Crutch, S., Dartigues, J., Duyckaerts, C., Epelbaum, S., Frisoni, G. B., Gauthier, S., Genthon, R., Gouw, A. A., Habert, M., Holtzman, D. M., Kivipelto, M., Lista, S., Molinuevo, J., O'Bryant, S. E., Rabinovici, G. D., Rowe, C., Salloway, S., Schneider, L. S., Sperling, R., Teichmann, M., Carrillo, M. C., Cummings, J., Jack, C. R., & Proceedings of the Meeting of the International Working Group (IWG) and the American Alzheimer's Association on “The Preclinical State of AD”; July 23, 2. W. D.
- Affiliations
- Sorbonne Université (FR)
- University of British Columbia (CA)
- Amsterdam Neuroscience (NL)
- University of Southern California (US)
- Université Toulouse III - Paul Sabatier (FR)
- Institut du Cerveau (FR)
- Centre National de la Recherche Scientifique (FR)
- Institute for Integrative and Experimental Genomics (DE)
- Sahlgrenska University Hospital (SE)
- Federal Institute for Drugs and Medical Devices (DE)
- Centro San Giovanni di Dio Fatebenefratelli (IT)
- UCL Queen Square Institute of Neurology (GB)
- Université de Bordeaux (FR)
- University of Geneva (CH)
- Douglas Mental Health University Institute (CA)
- Fondation pour la Recherche sur Alzheimer Hôpital Pitié‐Salpêtrière Paris France
- Washington University in St. Louis (US)
- Karolinska University Hospital (SE)
- AXA Research Fund (FR)
- Alzheimer's Disease and Other Cognitive Disorders Unit, Hospital Clínic Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) Barcelona Spain
- Center for Alzheimer's & Neurodegenerative Disease Research University of North Texas Health Science Center TX USA
- University of California, San Francisco (US)
- The University of Melbourne (AU)
- Brown University (US)
- Brigham and Women's Hospital (US)
- The Alzheimer's Association Division of Medical & Scientific Relations Chicago USA
- Cleveland Clinic (US)
- Department of Radiology Mayo Clinic Rochester MN USA
- Corresponding author
- Dubois, Bruno
- ORCID
- Dubois, Bruno
- Hampel, Harald
- Feldman, Howard H.
- Scheltens, Philip
- Andrieu, Sandrine
- Bakardjian, Hovagim
- Benali, Habib
- Bertram, Lars
- Blennow, Kaj
- Broich, Karl
- Cavedo, Enrica
- Crutch, Sebastian
- Dartigues, Jean‐François
- Duyckaerts, Charles
- Epelbaum, Stéphane
- Frisoni, Giovanni B.
- Gauthier, Serge
- Gouw, Alida A.
- Habert, Marie‐Odile
- Holtzman, David M.
- Kivipelto, Miia
- Lista, Simone
- Rabinovici, Gil D.
- Rowe, Christopher
- Salloway, Stephen
- Schneider, Lon S.
- Sperling, Reisa
- Teichmann, Marc
- Cummings, Jeffrey
- Venue
- Alzheimer's & Dementia
- Publisher
- Wiley
- Published
- 2016-03
- Volume
- 12
- Issue
- 3
- Pages
- 292-323
- ISSN
- 1552-5260 (ISSN-L)
- 1552-5279
- PMC
- PMC6417794
- OpenAlex
- W2309442902
- Cited by
- 1,925
- References
- 298
- Citations by year
- 2026: 115 · 2025: 176 · 2024: 244 · 2023: 245 · 2022: 247 · 2021: 244 · 2020: 176 · 2019: 157 · 2018: 161 · 2017: 112 · 2016: 47
- FWCI
- 22.78
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Alzheimer s & Dementia (publishedVersion)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Pure Amsterdam UMC (submittedVersion, other-oa)
- eScholarship (California Digital Library) (submittedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- AXA Research Fund
- National Institute on Aging
- Alzheimer's Association
- 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
- Health Sciences › Medicine › Oncology › Cancer-related cognitive impairment studies
- Keywords
- preclinical Alzheimer's disease, Alzheimer's disease continuum
- MeSH terms
- Alzheimer Disease, Animals, Brain, Humans, Disease Progression
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
