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Heterogeneity in mild cognitive impairment: Differences in neuropsychological profile and associated white matter lesion pathology
Open accessAbstract
This study examined whether distinct neuropsychological profiles could be delineated in a sample with Mild Cognitive Impairment (MCI) and whether white matter lesion (WML) burden contributed to MCI group differences. A heterogeneous, clinical sample of 70 older adults diagnosed with MCI was assessed using cognitive scores, and WML was quantified using a semi-automated, volumetric approach on T 2-weighted fluid-attenuated inversion recovery (FLAIR) images. Using cluster and discriminant analyses, three distinct groups (Memory/Language, Executive/Processing Speed, and Pure Memory) were empirically derived based on cognitive scores. Results also showed a dose dependent relationship of WML burden to MCI subgroup, with the Executive/Processing Speed subgroup demonstrating significantly higher levels of WML pathology when compared to the other subgroups. In addition, there was a dissociation of lesion type by the two most impaired subgroups (Memory/Language and Executive/Processing Speed) such that the Memory/Language subgroup showed higher periventricular lesion (PVL) and lower deep white matter lesion (DWML) volumes, whereas the Executive/Processing Speed demonstrated higher DWML and lower PVL volumes. Results demonstrate that distinct MCI subgroups can be empirically derived and reliably differentiated from a heterogeneous MCI sample, and that these profiles differ according to WML burden. Overall, findings suggest different underlying pathologies within MCI and contribute to our understanding of MCI subtypes. (JINS, 2009,15, 906–914.)
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“Applying these methods to different samples of individuals with clinically-diagnosed MCI, Delano-Wood et al. [27] and Libon et al. [28] independently identified three clusters that represented amnestic, dysexecutive, and mixed (i.e., memory and language deficits) MCI subtypes.”
From Neuropsychological Criteria for Mild Cognitive Impairment Improves Diagnostic Precision, Biomarker Associations, and Progression Rates (2014) · cites this paper as [27]
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Hierarchical Grouping to Optimize an Objective Function
Ward, J. H. (1963) · Journal of the American Statistical Association · doi:10.1080/01621459.1963.10500845 · Cited by 21,341 · cited 1×
“Ward’s minimum variance cluster analysis (Kaufman & Rousseau, 1990 ; Ward, 1963 ) was performed to identify patterns of impairment and assess for the presence of groups based on neuropsychological performance.”
MethodDevelopment and validation of a geriatric depression screening scale: a preliminary report
Yesavage, J. A., Brink, T. L., Rose, T. L., Lum, O., Huang, V., Adey, M., & Leirer, V. O. (1982) · Journal of Psychiatric Research · doi:10.1016/0022-3956(82)90033-4 · Cited by 15,025 · cited 1×
“Finally, we employed the 15-item Geriatric Depression Scale (GDS; Yesavage et al., 1983 ), a brief measure widely used to assess depression in older adult samples.”
MethodMild Cognitive Impairment: Clinical Characterization and Outcome
Petersen, R. C., Smith, G. E., Waring, S. C., Ivnik, R. J., Tangalos, E. G., & Kokmen, E. (1999) · Archives of Neurology · doi:10.1001/archneur.56.3.303 · Cited by 8,980
Applied Regression Analysis and Other Multivariable Methods
Walker, E., Kleinbaum, D. G., Kupper, L. L., & Muller, K. E. (1989) · Technometrics · doi:10.2307/1270375 · Cited by 8,538
Mild cognitive impairment as a diagnostic entity
Petersen, R. C. (2004) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2004.01388.x · Cited by 7,864
Finding Groups in Data: An Introduction to Cluster Analysis
Kaufman, L., & Rousseeuw, P. J. (1990) · Wiley Series in Probability and Statistics · doi:10.1002/9780470316801 · Cited by 7,344
Current concepts in mild cognitive impairment
Petersen, R. C., Doody, R., Kurz, A., Mohs, R. C., Morris, J. C., Rabins, P. V., Ritchie, K., Rossor, M., Thal, L., & Winblad, B. (2001) · Archives of Neurology · doi:10.1001/archneur.58.12.1985 · Cited by 4,781 · cited 1×
“…the concept of Mild Cognitive Impairment (MCI), a clinical construct thought to represent a transitional state between normal aging and dementia (Petersen et al., 1999 ; 2001 ), it became apparent that the original defi nition requiring a strict memory impairment was limiting and restrictive.”
BackgroundFrontal-subcortical circuits and human behavior
Cummings, J. L. (1993) · Archives of Neurology · doi:10.1001/archneur.1993.00540080076020 · Cited by 2,262
Aging Gracefully: Compensatory Brain Activity in High-Performing Older Adults
Cabeza, R., Anderson, N. D., Locantore, J. K., & McIntosh, A. R. (2002) · NeuroImage · doi:10.1006/nimg.2002.1280 · Cited by 1,964
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- Petersen, 2004, MCI as a useful clinical concept, Geriatric Times, 5, 1
- Reitan, 1985, The Halstead-Reitan Neuropsychological Test Battery: Theory and interpretation.
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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 772
“…, and mixed MCI subtypes MCI had been determined using the actuarial neuropsychological method, consistent with the of Delano-Wood et al. [27] and Libon et al. [ In contrast, when MCI had been determined the conventional “one test” MCI criteria, Clark sub-types, and a third…”
Self-citationNeuropsychological Assessment of Dementia
Salmon, D. P., & Bondi, M. W. (2008) · Annual Review of Psychology · doi:10.1146/annurev.psych.57.102904.190024 · Cited by 491
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
“A hierarchical cluster analysis was performed on the z scores using Ward’s method, consistent with previous MCI studies [4,5].”
MethodSelf-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
“…demonstrate deficits primarily in one area of cognitive ability (e.g., memory, executive functioning, language), while others demonstrate impairments in multiple cognitive domains (Bondi et al., 2014; Clark et al., 2013; Delano-Wood et al., 2009; Edmonds et al., 2014; Libon et al., 2010).”
Self-citationSubtle Cognitive Decline and Biomarker Staging in Preclinical Alzheimer’s Disease
Edmonds, E. C., Initiative, A. D. N., Delano‐Wood, L., Galasko, D. R., Salmon, D. P., & Bondi, M. W. (2015) · Journal of Alzheimer s Disease · doi:10.3233/jad-150128 · Cited by 205
“: +1 858 552 8585/Ext. 2809; Fax: +1 858 642 1218; E-mail: mbondi@ucsd.edu.”
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Metadata
- Authors
- DELANO-WOOD, L., BONDI, M. W., SACCO, J., ABELES, N., JAK, A. J., LIBON, D. J., & BOZOKI, A.
- Affiliations
- University of California San Diego (US)
- Michigan State University (US)
- Drexel University (US)
- Venue
- Journal of the International Neuropsychological Society
- Publisher
- Cambridge University Press (CUP)
- Published
- 2009-11
- Volume
- 15
- Issue
- 6
- Pages
- 906-914
- ISSN
- 1355-6177 (ISSN-L)
- 1469-7661
- PMC
- PMC3034688
- OpenAlex
- W2022434347
- Semantic Scholar
- 9643c2f0ad3e905372f28afdbac9c929a53e6e30
- Cited by
- 155
- References
- 59
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 6 · 2023: 9 · 2022: 6 · 2021: 22 · 2020: 11 · 2019: 16 · 2018: 11 · 2017: 11 · 2016: 8 · 2015: 10 · 2014: 11 · 2013: 5 · 2012: 11
- FWCI
- 4.73
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of the International Neuropsychological Society (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- University of California, San Diego
- National Institute on Aging (R01AG012674, K24AG026431)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Health Sciences › Medicine › Oncology › Cancer-related cognitive impairment studies
- Keywords
- mild cognitive impairment, MCI subtypes, white matter lesions, neuropsychological profile, executive function, processing speed, memory impairment, language impairment, periventricular white matter lesions, deep white matter lesions, FLAIR MRI, older adults, dementia risk
- MeSH terms
- Aged, Aged, 80 and over, Analysis of Variance, Brain, Cognition Disorders, Female, Humans, Magnetic Resonance Imaging, Male, Memory, Nerve Fibers, Myelinated, Neuropsychological Tests, Visual Perception, Discriminant Analysis
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