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The diagnosis of dementia due to Alzheimer's disease: Recommendations from the National Institute on Aging‐Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease
Open accessAbstract
The National Institute on Aging and the Alzheimer's Association charged a workgroup with the task of revising the 1984 criteria for Alzheimer's disease (AD) dementia. The workgroup sought to ensure that the revised criteria would be flexible enough to be used by both general healthcare providers without access to neuropsychological testing, advanced imaging, and cerebrospinal fluid measures, and specialized investigators involved in research or in clinical trial studies who would have these tools available. We present criteria for all‐cause dementia and for AD dementia. We retained the general framework of probable AD dementia from the 1984 criteria. On the basis of the past 27 years of experience, we made several changes in the clinical criteria for the diagnosis. We also retained the term possible AD dementia, but redefined it in a manner more focused than before. Biomarker evidence was also integrated into the diagnostic formulations for probable and possible AD dementia for use in research settings. The core clinical criteria for AD dementia will continue to be the cornerstone of the diagnosis in clinical practice, but biomarker evidence is expected to enhance the pathophysiological specificity of the diagnosis of AD dementia. Much work lies ahead for validating the biomarker diagnosis of AD dementia.
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“A consensus meeting was held among the study neurologists and neuropsychologists to clinically determine each potential participant’s cognitive status grouping (NC, MCI, or dementia) based on a standardized approach used in National Institute of Health (NIH)-funded Alzheimer’s Disease Centers across the United States (Albert et al., 2011; Jack et al., 2011; McKhann et al., 2011).”
From Internet-Based Conversational Engagement Randomized Controlled Clinical Trial (I-CONECT) Among Socially Isolated Adults 75+ Years Old With Normal Cognition or Mild Cognitive Impairment: Topline Results (2024) · cites this paper as McKhann et al., 2011
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“the atrophy of specific brain regions shown by structural MRI is an important part of the diagnostic criteria for FTD and AD (McKhann et al., 2011; Rascovsky et al., 2011)”
From Deep Learning-Based Classification and Voxel-Based Visualization of Frontotemporal Dementia and Alzheimer's Disease (2021) · cites this paper as McKhann et al., 2011
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Diagnosis of AD was made in accordance with the NINCDS-ADRCA criteria (McKhann et al., 2011) and MCI was diagnosed according to the Mayo criteria (Petersen et al., 1999).”
From Mean diffusivity in cortical gray matter in Alzheimer's disease: The importance of partial volume correction (2018) · cites this paper as McKhann et al., 2011
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“During this extended preclinical period prior to the dementia diagnosis, many patients develop behavioral or neuropsychiatric changes, including agitation, irritability, decreased motivation, loss of empathy, and depression, which increase the risk of transition to mild cognitive impairment and AD.12-14”
From Machine learning reveals prominent spontaneous behavioral changes and treatment efficacy in humanized and transgenic Alzheimer's disease models (2024) · cites this paper as [12]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“All patients (n = 96) were clinically evaluated by expert neurologists (M.G., D.J.I.) at the time of recording at the frontotemporal degeneration center (FTDC) in the neurology department of the Hospital of the University of Pennsylvania, and they were classified at a weekly consensus meeting at the FTDC using established clinical criteria.”
From Automatic classification of AD pathology in FTD phenotypes using natural speech (2024) · cites this paper as [26]
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In the citing paper
“AD is clinically diagnosed using the 2011 National Institute on Aging-Alzheimer's Association (NIA-AA) criteria [5].”
From Identification of novel diagnostic panel for mild cognitive impairment and Alzheimer’s disease: findings based on urine proteomics and machine learning (2023) · cites this paper as [5]
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In the citing paper
“Probable AD diagnoses were assigned according to both NINCDS/ADRDA criteria (23), and the core clinical NIA-AA criteria (28).”
From SUCLG2 identified as both a determinator of CSF Aβ1–42 levels and an attenuator of cognitive decline in Alzheimer's disease (2014) · cites this paper as [28]
In the citing paper
“The University of California San Francisco (UCSF) Memory and Aging Center Dementia cohort consisted of 152 carefully phenotyped older adults meeting the National Institute on Aging-Alzheimer's Association (NIA-AA) criteria for either mild-cognitive impairment22 or probable dementia because of AD.23”
From Whole-genome sequencing suggests a chemokine gene cluster that modifies age at onset in familial Alzheimer's disease (2015) · cites this paper as [23]
In the citing paper
“More recently, the imaging of amyloid with compounds such as the radiolabeled Pittsburgh compound B (11C-PiB) has received much interest and been proposed as a biomarker of AD.21,22”
From Diagnostic Criteria for Vascular Cognitive Disorders: A VASCOG Statement (2014) · cites this paper as [21]
In the citing paper
“These, along with amyloid imaging using positron emission tomography (PET), may help determine AD as the main or contributory cause of the cognitive disorder.”
From Diagnostic Criteria for Vascular Cognitive Disorders: A VASCOG Statement (2014) · cites this paper as [21]
In the citing paper
“CSF markers for AD are, however, better developed, with lower levels of Aβ42 and elevated levels of tau/phosphorylated-tau being indicative of AD pathology.21,22”
From Diagnostic Criteria for Vascular Cognitive Disorders: A VASCOG Statement (2014) · cites this paper as [21]
In the citing paper
“The clinical criteria used most commonly are the NIA‐AA criteria for dementia 89 and mild cognitive impairment 90 due to Alzheimer's disease.”
From Mental health care for older adults: recent advances and new directions in clinical practice and research (2022) · cites this paper as [89]
In the citing paper
“The development of the DSM-5 criteria for the various subtypes involved extensive discussions with experts from diverse fields to harmonize the DSM criteria with criteria developed by other expert groups, such as the NIA-AA, 20,27 the frontotemporal dementia expert group, 28,29 the consortium on DLB, 30 the VASCOG working group, 31 the Movement Disorder Study Task Force on Parkinson Disease 32 and”
From Classifying neurocognitive disorders: the DSM-5 approach (2014) · cites this paper as [27]
In the citing paper
“This different pattern of results in bvFTD and AD may reflect the preferential and widespread damage within the AIN in bvFTD11,14,16, 17, 18, 19, 20,24 whereas in AD, AIN damage appears to be more circumscribed.17,38,88”
From Altered spatiotemporal brain dynamics of interoception in behavioural-variant frontotemporal dementia (2025) · cites this paper as [38]
In the citing paper
“Second, patients received diagnoses based on established clinical criteria only,37,38 without testing for ATN biomarkers in AD such as the deposition of amyloid-β and tau proteins established via Positron Emission Tomography, CSF, or plasma in AD.94, 95, 96, 97”
From Altered spatiotemporal brain dynamics of interoception in behavioural-variant frontotemporal dementia (2025) · cites this paper as [38]
In the citing paper
“The diagnosis was concluded in a multidisciplinary meeting using consensus criteria for probable FTD, PPD (DSM-V), and AD [25,31,32].”
In the citing paper
“Detection of abnormal Aβ accumulation (Aβ positivity) may support the clinical diagnosis of AD1,2 and is essential for including participants in clinical AD trials targeting Aβ.3”
From Performance of Fully Automated Plasma Assays as Screening Tests for Alzheimer Disease–Related β-Amyloid Status (2019) · cites this paper as [2]
In the citing paper
“Diagnosis was established by the multidisciplinary teams at each research institute based on current consensus diagnostic criteria (McKhann et al., 2011; Postuma et al., 2015; Rascovsky et al., 2011).”
From Thinking versus feeling: How interoception and cognition influence emotion recognition in behavioural-variant frontotemporal dementia, Alzheimer's disease, and Parkinson's disease (2023) · cites this paper as McKhann et al., 2011
In the citing paper
“AD patients present with predominant episodic memory loss and impaired executive functioning, with atrophy observed in the medial temporal lobe, most notably in the hippocampus and posterior cingulate (McKhann et al., 2011).”
From Thinking versus feeling: How interoception and cognition influence emotion recognition in behavioural-variant frontotemporal dementia, Alzheimer's disease, and Parkinson's disease (2023) · cites this paper as McKhann et al., 2011
In the citing paper
“A diagnosis of probable AD had been made prior to the study by neurologists at the Memory Center according to the clinical criteria of the National Institute on Aging and the Alzheimer’s Association criteria for probable AD [1].”
From The effects of confinement on neuropsychiatric symptoms in Alzheimer's disease during the COVID-19 crisis (2020) · cites this paper as [1]
In the citing paper
“The 3 major clinical criteria for the AD spectrum are the revised 2011 NIA-AA criteria, 32,39 the International Working Group (Dubois and colleagues 39,40 ) 2010 revised new lexicon criteria, and the Diagnostic and Statistical Manual of Mental Disorders, 5th edition criteria.41”
From The Alzheimer’s Disease Clinical Spectrum (2019) · cites this paper as [32]
In the citing paper
“The 2011 National Institute on Aging and Alzheimer's Association (NIA-AA) criteria for AD recognizes nonamnestic AD presentations that include language, visuospatial, and executive dysfunction features.32”
From The Alzheimer’s Disease Clinical Spectrum (2019) · cites this paper as [32]
In the citing paper
“dementia-level impairment requires cognitive or behavioral symptoms”
From The Alzheimer’s Disease Clinical Spectrum (2019) · cites this paper as [32]
In the citing paper
“MCI diagnosis is a matter of”
From The Alzheimer’s Disease Clinical Spectrum (2019) · cites this paper as [32]
In the citing paper
“With the advent of biomarkers that enable in vivo identification of underlying AD pathological conditions, and the acceptance that AD begins years before the emergence of cognitive impairment, AD is now commonly accepted as a clinicopathological entity7,8 that can be diagnosed without histopathological examination, in the presence of appropriate biomarker evidence of an underlying condition.6,8,9”
From Positron Emission Tomography Imaging With [ 18 F]flortaucipir and Postmortem Assessment of Alzheimer Disease Neuropathologic Changes (2020) · cites this paper as [8]
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“AD usually presents with deficits in short-term memory formation and disturbance of additional cognitive functions including word-finding, spatial orientation, reasoning, judgement, and problem-solving (Karantzoulis and Galvin, 2011; McKhann et al., 2011).”
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“The AD cohort included patients with “probable Alzheimer’s disease” according to National Institute on Aging-Alzheimer’s Association criteria, supported by at least an intermediate level of evidence for AD pathology by CSF analysis or imaging [18].”
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“The current practice guideline is to incorporate structural imaging as part of the diagnostic evaluation for AD [2, 3] to exclude other conditions.”
BackgroundMethodInfluential
Metadata
- Authors
- McKhann, G. M., Knopman, D. S., Chertkow, H., Hyman, B. T., Jack, C. R., Kawas, C. H., Klunk, W. E., Koroshetz, W. J., Manly, J. J., Mayeux, R., Mohs, R. C., Morris, J. C., Rossor, M. N., Scheltens, P., Carrillo, M. C., Thies, B., Weintraub, S., & Phelps, C. H.
- Affiliations
- Johns Hopkins University (US)
- Mayo Clinic (US)
- Lady Davis Institute for Medical Research (CA)
- Harvard University (US)
- University of California, Irvine (US)
- University of Pittsburgh (US)
- National Institute of Neurological Disorders and Stroke (US)
- Columbia University Irving Medical Center (US)
- Eli Lilly (United States) (US)
- Washington University in St. Louis (US)
- UCL Queen Square Institute of Neurology (GB)
- Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
- Alzheimer's Association Chicago IL USA
- Alzheimer's Association (US)
- Department of Psychiatry Northwestern Feinberg School of Medicine Chicago IL USA
- National Institutes of Health (US)
- Corresponding author
- McKhann, Guy M.
- ORCID
- Venue
- Alzheimer's & Dementia
- Publisher
- Wiley
- Published
- 2011-04-22
- Volume
- 7
- Issue
- 3
- Pages
- 263-269
- ISSN
- 1552-5260 (ISSN-L)
- 1552-5279
- PMC
- PMC3312024
- OpenAlex
- W2115017507
- Semantic Scholar
- 37d2d04f8c09da1f0cf8434a38a51841b5b703bf
- Cited by
- 18,657
- References
- 44
- Citations by year
- 2026: 893 · 2025: 1313 · 2024: 1585 · 2023: 1543 · 2022: 1670 · 2021: 1796 · 2020: 1602 · 2019: 1448 · 2018: 1297 · 2017: 1200 · 2016: 1088 · 2015: 1062 · 2014: 794 · 2013: 715 · 2012: 491
- FWCI
- 471.77
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Alzheimer s & Dementia (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Digital Academic REpository of VU University Amsterdam (Vrije Universiteit Amsterdam) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- National Institute on Aging
- Forest Pharmaceuticals
- Alzheimer's Association
- Fidelity Biosciences
- Baxter International
- Pfizer
- Johnson and Johnson
- Avid Radiopharmaceuticals
- GE Healthcare
- 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
- Alzheimer's disease, dementia diagnosis
- MeSH terms
- Alzheimer Disease, Diagnosis, Differential, Diagnostic Imaging, Humans, Societies, Medical, United States, Biomarkers, Practice Guidelines as Topic, Disease Progression, National Institute on Aging (U.S.)
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