Are Empirically-Derived Subtypes of Mild Cognitive Impairment Consistent with Conventional Subtypes?
Open accessAbstract
Given the importance of identifying dementia prodromes for future treatment efforts, we examined two methods of diagnosing mild cognitive impairment (MCI) and determined whether empirically-derived MCI subtypes of these diagnostic methods were consistent with one another as well as with conventional MCI subtypes (i.e., amnestic, non-amnestic, single-domain, multi-domain). Participants were diagnosed with MCI using either conventional Petersen/Winblad criteria (n = 134; >1.5 SDs below normal on one test within a cognitive domain) or comprehensive neuropsychological criteria developed by Jak et al. (2009) (n = 80; >1 SD below normal on two tests within a domain), and the resulting samples were examined via hierarchical cluster and discriminant function analyses. Results showed that neuropsychological profiles varied depending on the criteria used to define MCI. Both criteria revealed an Amnestic subtype, consistent with prodromal Alzheimer's disease (AD), and a Mixed subtype that may capture individuals in advanced stages of MCI. The comprehensive criteria uniquely yielded Dysexecutive and Visuospatial subtypes, whereas the conventional criteria produced a subtype that performed within normal limits, suggesting its susceptibility to false positive diagnostic errors. Whether these empirically-derived MCI subtypes correspond to dissociable neuropathologic substrates and represent reliable prodromes of dementia will require additional follow-up.
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
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 Cluster-Derived Normal group in Clark et al. included nearly half of the 'one test' MCI sample and did not differ from a normal control group in cognition or neuroimaging measures.
“This Cluster-Derived Normal group included nearly half of the “one test” MCI sample and did not differ from a normal control group in terms of cognition or neuroimaging measures of cortical thickness in areas usually affected in MCI or AD.”
From Neuropsychological Criteria for Mild Cognitive Impairment Improves Diagnostic Precision, Biomarker Associations, and Progression Rates (2014) · cites this paper as [31]
Clark et al. observed amnestic and mixed MCI subtypes and a third cluster-derived normal subtype when MCI was determined using conventional 'one test' criteria.
“In contrast, when MCI had been determined using the conventional “one test” MCI criteria, Clark et al. [31] observed amnestic and mixed MCI subtypes, and a third cluster-derived normal subtype that performed within normal limits across all neuropsychological measures.”
From Neuropsychological Criteria for Mild Cognitive Impairment Improves Diagnostic Precision, Biomarker Associations, and Progression Rates (2014) · cites this paper as [31]
Clark et al. found that conventional 'one test' MCI criteria identified more participants as having MCI (n=134) than actuarial neuropsychological criteria (n=80).
“The conventional “one test” MCI criteria identified more participants as having MCI (n = 134) than did the actuarial neuropsychological criteria (n = 80).”
From Neuropsychological Criteria for Mild Cognitive Impairment Improves Diagnostic Precision, Biomarker Associations, and Progression Rates (2014) · cites this paper as [31]
One caveat of our study was the absence of assessing other cognitive domains like visuospatial functions.
“One caveat of our study was the absence of assessing other cognitive domains like that of visuospatial functions, particularly since we have previously identified a visuospatial MCI subtype [31] and Ferman et al. [19] have shown that baseline MCI diagnoses based on visuospatial deficits reliably predict development of dementia with Lewy bodies.”
From Neuropsychological Criteria for Mild Cognitive Impairment Improves Diagnostic Precision, Biomarker Associations, and Progression Rates (2014) · cites this paper as [31]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Diagnosis and management of dementia with Lewy bodies: Third report of the DLB consortium
McKeith, I. G., Dickson, D. W., Lowe, J., Emre, M., O'Brien, J. T., Feldman, H., Cummings, J., Duda, J. E., Lippa, C., Perry, E. K., et al. (2005) · Neurology · doi:10.1212/01.wnl.0000187889.17253.b1 · Cited by 5,069 · see citing works
Gorelick, P. B., Scuteri, A., Black, S. E., DeCarli, C., Greenberg, S. M., Iadecola, C., Launer, L. J., Laurent, S., Lopez, O. L., Nyenhuis, D., et al. (2011) · Stroke · doi:10.1161/str.0b013e3182299496 · Cited by 3,811 · see citing works
Delis-Kaplan Executive Function System
Delis, D. C., Kaplan, E., & Kramer, J. H. (2012) · PsycTESTS Dataset · doi:10.1037/t15082-000 · Cited by 2,683 · see citing works
Mitchell, A. J., & Shiri‐Feshki, M. (2009) · Acta Psychiatrica Scandinavica · doi:10.1111/j.1600-0447.2008.01326.x · Cited by 1,659 · cited 1× · see citing works
“Although MCI is considered a risk factor for AD, many individuals diagnosed with MCI may remain stable, progress to a non-AD dementia such as vascular dementia (VaD) (Mitchell & Shiri-Feshki, 2009), or show improvement on cognitive tests upon follow-up (Loewenstein et al., 2009).”
Grundman, M. (2004) · Archives of Neurology · doi:10.1001/archneur.61.1.59 · Cited by 972 · see citing works
Vascular burden and Alzheimer disease pathologic progression
Lo, R. Y., Jagust, W. J., Weiner, M., Aisen, P., Weiner, M., Aisen, P., Petersen, R., Jack, C. R., Jagust, W., Trojanowki, J. Q., et al. (2012) · Neurology · doi:10.1212/wnl.0b013e31826c1b9d · Cited by 156 · see citing works
DELANO-WOOD, L., BONDI, M. W., SACCO, J., ABELES, N., JAK, A. J., LIBON, D. J., & BOZOKI, A. (2009) · Journal of the International Neuropsychological Society · doi:10.1017/s1355617709990257 · Cited by 155 · cited 5× · see citing works
“Consistent with recent clinical studies of MCI (Delano-Wood et al., 2009), Ward’s method was used to calculate the distance between each cluster (squared Euclidean distance) and merge clusters together that produced the smallest increase in overall distances within clusters.”
InfluentialSelf-citationBase Rates of “Impaired” Neuropsychological Test Performance Among Healthy Older Adults
Palmer, B. (1998) · Archives of Clinical Neuropsychology · doi:10.1016/s0887-6177(97)00037-1 · Cited by 142 · see citing works
Flagged first, then by citations
Research works printed but not linked: 37
- Bartley M Bokde AL Ewers M Faluyi YO Tobin WO Snow A O’Neill D 2012 Subjective memory complaints in community dwelling health older people: The influence of brain and psychopathology International Journal of Geriatric Psychiatry 27 836 843 21953807
- Bickel H Mosch E Seigerschmidt E Siemen M Forstl H 2006 Prevalence and persistence of mild cognitive impairment among elderly patients in general hospitals Dementia and Geriatric Cognitive Disorders 21 4 242 250 16465052
- Binder LM Iverson GL Brooks BL 2009 To err is human: “Abnormal” neuropsychological scores and variability are common in healthy adults Archives of Clinical Neuropsychology 24 31 46 19395355
- Busse A Hensel A Guhne U Angermeyer MC Riedel-Heller SG 2006 Mild cognitive impairment: Long-term course of four clinical subtypes Neurology 67 2176 2185 17190940
- Calderon J Perry RJ Erzinclioglu SW Berrios GE Dening TR Hodges JR 2001 Perception, attention, and working memory are disproportionately impaired in dementia with Lewy bodies compared with Alzheimer’s disease Journal of Neurology, Neurosurgery, and Psychiatry 70 157 164 PMC1737215 11160462
- Chung JC Man DW 2009 Self-appraised, informant-reported, and objective memory and cognitive function in mild cognitive impairment Dementia and Geriatric Cognitive Disorders 27 187 193 19202338
- Collerton D Burn D McKeith I O’Brien J 2003 Systematic review and meta-analysis show that dementia with Lewy bodies is a visual-perceptual and attentional-executive dementia Dementia & Geriatric Cognitive Disorders 16 229 237 14512718
- Delano-Wood L Abeles N Sacco JM Wierenga CE Horne NR Bozoki A 2008 Regional white matter pathology in mild cognitive impairment – Differential influence of lesion type on neuropsychological functioning Stroke 39 794 799 18258826
- Delis DC Kramer JH Kaplan E Ober BA 2000 California Verbal Learning Test: Second Edition San Antonio, TX The Psychological Corporation
- Eppig J Wambach DM Nieves C Price CC Lamar M Delano-Wood L Libon DJ 2012 Dysexecutive functioning in mild cognitive impairment: Derailment in temporal gradients Journal of the International Neuropsychological Society 18 20 28 22014116 PMC3315354
- Ganguli M Snitz BE Saxton JA Chang CCH Lee CW Vander Bilt J Petersen RC 2011 Outcomes of mild cognitive impairment by definition: A population study Archives of Neurology 68 761 767 21670400 PMC3135309
- Geerlings MI Appelman AP Vincken KL Mali WP van der Graaf Y SMART Study Group 2009 Association of white matter lesions and lacunar infarcts with executive functioning: The SMART-MR study American Journal of Epidemiology 170 9 1147 1155 19783584
- Harwood DG Barker WW Ownby RL Mullan M Duara R 2004 No association between subjective memory complaints and apolipoprotein E genotype in cognitively intact elderly International Journal of Geriatric Psychiatry 19 1131 1139 15526312
- Jak AJ Bondi MW Delano-Wood L Wierenga C Corey-Bloom J Salmon DP Delis DC 2009 Quantification of five neuropsychological approaches to defining mild cognitive impairment American Journal of Geriatric Psychiatry 17 5 368 375 19390294 PMC2743175
- Jellinger KA Attems J 2010 Prevalence of dementia disorders in the oldest-old: An autopsy study Acta Neuropathologica 119 421 433 20204386
- Lenehan ME Klekociuk SZ Summers MJ 2012 Absence of a relationship between subjective memory complaint and objective memory impairment in mild cognitive impairment (MCI): Is it time to abandon subjective memory complaint as an MCI diagnostic criterion? International Psychogeriatrics 24 1505 1514 22717042
- Libon DJ Bondi MW Price CC Lamar M Eppig J Wambach DM Penney DL 2011 Verbal serial list learning in mild cognitive impairment: A profile analysis of interference, forgetting, and errors Journal of the International Neuropsychological Society 17 905 914 21880171 PMC3315271
- Libon DJ Xie SX Eppig J Wicas G Lamar M Lippa C Wambach DM 2010 The heterogeneity of mild cognitive impairment: A neuropsychological analysis Journal of the International Neuropsychological Society 16 84 93 19887015
- Loewenstein DA Acevedo A Small BJ Agron J Crocco E Duara R 2009 Stability of different subtypes of mild cognitive impairment among the elderly over a 2- to 3- year follow-up period Dementia and Geriatric Cognitive Disorders 27 418 423 19365121 PMC2814021
- Luck T Luppa M Briel S Riedel-Heller SG 2010 Incidence of mild cognitive impairment: A systematic review Dementia & Geriatric Cognitive Disorders 29 164 175 20150735
- Manly JJ Tang MX Schupf N Stern Y Vonsattel JP Mayeux R 2008 Frequency and course of mild cognitive impairment in a multiethnic community Annals of Neurology 63 494 506 18300306 PMC2375143
- Petersen RC 2004 Mild cognitive impairment as a diagnostic entity Journal of Internal Medicine 256 183 194 15324362
- Petersen RC Morris JC 2005 Mild cognitive impairment as a clinical entity and treatment target Archives of Neurology 62 1160 1163 16009779
- Reijmer YD van den Berg E Dekker JM Niipels G Stehouwer CD Kappelle LJ Biessels GJ 2012 Development of vascular risk factors over 15 years in relation to cognition: The Hoorn Study Journal of the American Geriatric Society 60 8 1426 1433 22861348
- Reitan RM Wolfson D 1985 The Halstead-Reitan Neuropsychological Test Battery Tucson, AZ Neuropsychology Press
- Roberts RO Geda YE Knopman DS Cha RH Pankratz VS Boeve BF Petersen RC 2012 The incidence of MCI differs by subtype and is higher in men: The Mayo Clinic Study of Aging Neurology 78 342 351 22282647 PMC3280046
- Rountree SD Waring SC Chan WC Lupo PJ Darby EJ Doody RS 2007 Importance of subtle amnestic and non-amnestic deficits in mild cognitive impairments: Prognosis and conversion to dementia Dementia & Geriatric Cognitive Disorders 24 476 482 17992015
- Salmon DP Bondi MW 2009 Neuropsychological assessment of dementia Annual Review of Psychology 60 257 282 PMC2864104 18616392
- Savva GM Wharton SB Ince PG Forster G Matthews FE Brayne C 2009 Age, neuropathology, and dementia New England Journal of Medicine 360 2302 2309 19474427
- Schneider JA Arvanitakis Z Leurgans SE Bennett DA 2009 The neuropathology of probable Alzheimer disease and mild cognitive impairment Annals of Neurology 66 200 208 19743450 PMC2812870
- Schretlen DJ Testa SM Winicki JM Pearlson GD Gordon B 2008 Frequency and bases of abnormal performance by healthy adults on neuropsychological testing Journal of the International Neuropsychological Society 14 436 445 18419842
- Sinka L Kovari E Gold G Hof PR Herrmann FR Bouras C Giannakopoulos P 2010 Small vascular and Alzheimer disease-related pathologic determinants of dementia in the oldest-old Journal of Neuropathology and Experimental Neurology 69 1247 1255 21107137
- Slavin MJ Brodaty H Kochan NA Crawford JD Trollor JN Draper B Sachdev PS 2010 Prevalence and predictors of “subjective cognitive complaints” in the Sydney Memory and Ageing Study American Journal of Geriatric Psychiatry 18 701 710 21491631
- Summers MJ Saunders NL 2012 Neuropsychological measures predict decline to Alzheimer’s dementia from mild cognitive impairment Neuropsychology 26 498 508 22612573
- Ward A Arrighi HM Michels S Cedarbaum JM 2012 Mild cognitive impairment: Disparity of incidence and prevalence estimates Alzheimer’s & Dementia 8 14 21 22265588
- Winblad B Palmer K Kivipelto M Jelic V Fratiglioni L Wahlund LO Petersen RC 2004 Mild cognitive impairment – beyond controversies, towards a consensus: Report of the International Working Group on Mild Cognitive Impairment Journal of Internal Medicine 256 240 246 15324367
- Yesavage JA Brink TL Rose TL Lum O Huang V Adey MB Leirer VO 1983 Development and validation of a geriatric depression screening scale: A preliminary report Journal of Psychiatric Research 17 37 49 7183759
Cited by
Sorted by citations
Bondi, M. W., Initiative, F. T. A. D. N., Edmonds, E. C., Jak, A. J., Clark, L. R., Delano-Wood, L., McDonald, C. R., Nation, D. A., Libon, D. J., Au, R., et al. (2014) · Journal of Alzheimer's Disease · doi:10.3233/jad-140276 · Cited by 750 · see citing works
Self-citationAlzheimer’s Disease: Past, Present, and Future
Bondi, M. W., Edmonds, E. C., & Salmon, D. P. (2017) · Journal of the International Neuropsychological Society · doi:10.1017/s135561771700100x · Cited by 649 · see citing works
Self-citationEdmonds, E. C., Delano‐Wood, L., Clark, L. R., Jak, A. J., Nation, D. A., McDonald, C. R., Libon, D. J., Au, R., Galasko, D., Salmon, D. P., et al. (2015) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2014.03.005 · Cited by 256 · see citing works
Self-citationSubjective Cognitive Complaints Contribute to Misdiagnosis of Mild Cognitive Impairment
Edmonds, E. C., Delano-Wood, L., Galasko, D. R., Salmon, D. P., & Bondi, M. W. (2014) · Journal of the International Neuropsychological Society · doi:10.1017/s135561771400068x · Cited by 249 · see citing works
Self-citationZygouris, S., Giakoumis, D., Votis, K., Doumpoulakis, S., Ntovas, K., Segkouli, S., Karagiannidis, C., Tzovaras, D., & Tsolaki, M. (2015) · Journal of Alzheimer s Disease · doi:10.3233/jad-141260 · Cited by 158 · see citing works
Subtyping of mild cognitive impairment using a deep learning model based on brain atrophy patterns
Kwak, K., Giovanello, K. S., Bozoki, A., Styner, M., & Dayan, E. (2021) · Cell Reports Medicine · doi:10.1016/j.xcrm.2021.100467 · Cited by 47 · see citing works
Bangen, K. J., Initiative, F. T. A. D. N., Clark, A. L., Werhane, M., Edmonds, E. C., Nation, D. A., Evangelista, N., Libon, D. J., Bondi, M. W., & Delano-Wood, L. (2016) · Journal of Alzheimer's Disease · doi:10.3233/jad-150900 · Cited by 51 · see citing works
Self-citationOperationalizing mild cognitive impairment criteria in small vessel disease: the VMCI‐Tuscany Study
Salvadori, E., Poggesi, A., Valenti, R., Pracucci, G., Pescini, F., Pasi, M., Nannucci, S., Marini, S., Del Bene, A., Ciolli, L., et al. (2016) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2015.02.010 · Cited by 36 · see citing works
Fountain-Zaragoza, S., Braun, S. E., Horner, M. D., & Benitez, A. (2021) · Journal of Clinical and Experimental Neuropsychology · doi:10.1080/13803395.2021.2007857 · Cited by 12 · see citing works
- Authors
- Clark, L. R., Delano-Wood, L., Libon, D. J., McDonald, C. R., Nation, D. A., Bangen, K. J., Jak, A. J., Au, R., Salmon, D. P., & Bondi, M. W.
- Affiliations
- San Diego State University (US)
- Drexel University (US)
- UC San Diego Health System (US)
- United States Department of Veterans Affairs (US)
- Boston University (US)
- University of California San Diego (US)
- Corresponding author
- Bondi, Mark W.
- ORCID
- Venue
- Journal of the International Neuropsychological Society
- Publisher
- Cambridge University Press (CUP)
- Published
- 2013-04-03
- Volume
- 19
- Issue
- 6
- Pages
- 635-645
- ISSN
- 1355-6177 (ISSN-L)
- 1469-7661
- PMC
- PMC3742806
- OpenAlex
- W2084535048
- Cited by
- 167
- References
- 8
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 10 · 2023: 10 · 2022: 15 · 2021: 19 · 2020: 13 · 2019: 15 · 2018: 10 · 2017: 13 · 2016: 17 · 2015: 15 · 2014: 12 · 2013: 2
- FWCI
- 10.90
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Journal of the International Neuropsychological Society (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (P50AG005131, R01AG012674, K24AG026431)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cancer-related cognitive impairment studies
- Social Sciences › Psychology › Applied Psychology › Psychological Testing and Assessment
- Keywords
- mild cognitive impairment, MCI subtypes, amnestic MCI, executive dysfunction, visuospatial impairment, prodromal Alzheimer's disease, false-positive diagnosis
- MeSH terms
- Activities of Daily Living, Aged, Aged, 80 and over, Female, Humans, Male, Neuropsychological Tests, Cluster Analysis, Discriminant Analysis, Cognitive Dysfunction
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
