. 2015 Apr;11(4):415-24.

doi: 10.1016/j.jalz.2014.03.005. Epub 2014 May 22.

Susceptibility of the conventional criteria for mild cognitive impairment to false-positive diagnostic errors

Affiliations

¹ Department of Psychiatry, University of California San Diego, School of Medicine, La Jolla, CA, USA.
² Department of Psychiatry, University of California San Diego, School of Medicine, La Jolla, CA, USA; Veterans Affairs San Diego Healthcare System, San Diego, CA, USA.
³ San Diego State University/University of California San Diego Joint Doctoral Program in Clinical Psychology, San Diego, CA, USA.
⁴ Department of Psychology, University of Southern California, Los Angeles, CA, USA.
⁵ Department of Neurology, Drexel University, College of Medicine, Philadelphia, PA, USA.
⁶ Department of Neurology, Boston University, School of Medicine, Boston, MA, USA; Framingham Heart Study, Boston University, School of Medicine, Boston, MA, USA.
⁷ Department of Psychiatry, University of California San Diego, School of Medicine, La Jolla, CA, USA; Veterans Affairs San Diego Healthcare System, San Diego, CA, USA; Department of Neurosciences, University of California San Diego, School of Medicine, La Jolla, CA, USA.
⁸ Department of Neurosciences, University of California San Diego, School of Medicine, La Jolla, CA, USA.
⁹ Department of Psychiatry, University of California San Diego, School of Medicine, La Jolla, CA, USA; Veterans Affairs San Diego Healthcare System, San Diego, CA, USA. Electronic address: mbondi@ucsd.edu.

PMID: 24857234
PMCID: PMC4241187
DOI: 10.1016/j.jalz.2014.03.005

Susceptibility of the conventional criteria for mild cognitive impairment to false-positive diagnostic errors

Emily C Edmonds et al. Alzheimers Dement. 2015 Apr.

. 2015 Apr;11(4):415-24.

doi: 10.1016/j.jalz.2014.03.005. Epub 2014 May 22.

Affiliations

¹ Department of Psychiatry, University of California San Diego, School of Medicine, La Jolla, CA, USA.
² Department of Psychiatry, University of California San Diego, School of Medicine, La Jolla, CA, USA; Veterans Affairs San Diego Healthcare System, San Diego, CA, USA.
³ San Diego State University/University of California San Diego Joint Doctoral Program in Clinical Psychology, San Diego, CA, USA.
⁴ Department of Psychology, University of Southern California, Los Angeles, CA, USA.
⁵ Department of Neurology, Drexel University, College of Medicine, Philadelphia, PA, USA.
⁶ Department of Neurology, Boston University, School of Medicine, Boston, MA, USA; Framingham Heart Study, Boston University, School of Medicine, Boston, MA, USA.
⁷ Department of Psychiatry, University of California San Diego, School of Medicine, La Jolla, CA, USA; Veterans Affairs San Diego Healthcare System, San Diego, CA, USA; Department of Neurosciences, University of California San Diego, School of Medicine, La Jolla, CA, USA.
⁸ Department of Neurosciences, University of California San Diego, School of Medicine, La Jolla, CA, USA.
⁹ Department of Psychiatry, University of California San Diego, School of Medicine, La Jolla, CA, USA; Veterans Affairs San Diego Healthcare System, San Diego, CA, USA. Electronic address: mbondi@ucsd.edu.

PMID: 24857234
PMCID: PMC4241187
DOI: 10.1016/j.jalz.2014.03.005

Abstract

Background: We assessed whether mild cognitive impairment (MCI) subtypes could be empirically derived within the Alzheimer's Disease Neuroimaging Initiative (ADNI) MCI cohort and examined associated biomarkers and clinical outcomes.

Methods: Cluster analysis was performed on neuropsychological data from 825 MCI ADNI participants.

Results: Four subtypes emerged: (1) dysnomic (n = 153), (2) dysexecutive (n = 102), (3) amnestic (n = 288), and (4) cluster-derived normal (n = 282) who performed within normal limits on cognitive testing. The cluster-derived normal group had significantly fewer APOE ε4 carriers and fewer who progressed to dementia compared with the other subtypes; they also evidenced cerebrospinal fluid Alzheimer's disease biomarker profiles that did not differ from the normative reference group.

Conclusions: Identification of empirically derived MCI subtypes demonstrates heterogeneity in MCI cognitive profiles that is not captured by conventional criteria. The large cluster-derived normal group suggests that conventional diagnostic criteria are susceptible to false-positive errors, with the result that prior MCI studies may be diluting important biomarker relationships.

Keywords: Alzheimer's disease; Cluster analysis; Dementia; MCI; Mild cognitive impairment; Misclassification; Misdiagnosis; Neuropsychology.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr. Bondi serves as Associate Editor for the Journal of the International Neuropsychological Society. Dr. Galasko serves as Editor for Alzheimer’s Research and Therapy, and as a paid consultant on Data Safety Monitoring Boards for Pfizer, Inc., Elan, Inc., and Balance Pharmaceuticals, Inc. Dr. Salmon serves as a consultant for CHDI Foundation, Novartis, and Bristol-Meyers Squibb. The other authors report no disclosures.

Figures

**Fig. 1**
Neuropsychological performance for the cluster groups. Error bars denote standard deviations. The horizontal dotted line indicates the typical cutoff for impairment (−1.5 SDs).

**Fig. 2**
CSF (A) hyperphosphorylated tau (p-tau_181p) concentrations (B) beta-amyloid (Aβ_1-42) concentrations and (C) ratio of p-tau_181p/Aβ_1-42 for the cluster groups and normal control group. Error bars denote standard deviations.

**Fig. 3**
Hazard function showing risk of progression to dementia across time for the cluster groups.

See this image and copyright information in PMC

References

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Susceptibility of the conventional criteria for mild cognitive impairment to false-positive diagnostic errors

Affiliations

Susceptibility of the conventional criteria for mild cognitive impairment to false-positive diagnostic errors

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical

Miscellaneous