A double-dichotomy clustering of dual pathology dementia patients
Introduction: Subcortical ischemic vascular disease (SIVD) and Alzheimer's disease (AD) related dementia can coexist in older subjects, leading to mixed dementia (MX). Identification of dementia sub-groups is important for designing proper treatment plans and clinical trials. Method: An Alzheim...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-01-01
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| Series: | Cerebral Circulation - Cognition and Behavior |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666245021000088 |
| _version_ | 1797967690699112448 |
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| author | Arvind Caprihan Rajikha Raja Laura J. Hillmer Erik Barry Erhardt Jill Prestopnik Jeffrey Thompson John C Adair Janice E. Knoefel Gary A. Rosenberg |
| author_facet | Arvind Caprihan Rajikha Raja Laura J. Hillmer Erik Barry Erhardt Jill Prestopnik Jeffrey Thompson John C Adair Janice E. Knoefel Gary A. Rosenberg |
| author_sort | Arvind Caprihan |
| collection | DOAJ |
| description | Introduction: Subcortical ischemic vascular disease (SIVD) and Alzheimer's disease (AD) related dementia can coexist in older subjects, leading to mixed dementia (MX). Identification of dementia sub-groups is important for designing proper treatment plans and clinical trials. Method: An Alzheimer's disease severity (ADS) score and a vascular disease severity (VDS) score are calculated from CSF and MRI biomarkers, respectively. These scores, being sensitive to different Alzheimer's and vascular disease processes are combined orthogonally in a double-dichotomy plot. This formed an objective basis for clustering the subjects into four groups, consisting of AD, SIVD, MX and leukoaraiosis (LA). The relationship of these four groups is examined with respect to cognitive assessments and clinical diagnosis. Results: Cluster analysis had at least 83% agreement with the clinical diagnosis for groups based either on Alzheimer's or on vascular sensitive biomarkers, and a combined agreement of 68.8% for clustering the four groups. The VDS score was correlated to executive function (r = -0.28, p < 0.01) and the ADS score to memory function (r = −0.35, p < 0.002) after adjusting for age, sex, and education. In the subset of patients for which the cluster scores and clinical diagnoses agreed, the correlations were stronger (VDS score-executive function: r = −0.37, p < 0.006 and ADS score-memory function: r = −0.58, p < 0.0001). Conclusions: The double-dichotomy clustering based on imaging and fluid biomarkers offers an unbiased method for identifying mixed dementia patients and selecting better defined sub-groups. Differential correlations with neuropsychological tests support the hypothesis that the categories of dementia represent different etiologies. |
| first_indexed | 2024-04-11T02:34:01Z |
| format | Article |
| id | doaj.art-f1947581cbfd42d0bfbc7c89f31ec3d9 |
| institution | Directory Open Access Journal |
| issn | 2666-2450 |
| language | English |
| last_indexed | 2024-04-11T02:34:01Z |
| publishDate | 2021-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cerebral Circulation - Cognition and Behavior |
| spelling | doaj.art-f1947581cbfd42d0bfbc7c89f31ec3d92023-01-02T20:41:41ZengElsevierCerebral Circulation - Cognition and Behavior2666-24502021-01-012100011A double-dichotomy clustering of dual pathology dementia patientsArvind Caprihan0Rajikha Raja1Laura J. Hillmer2Erik Barry Erhardt3Jill Prestopnik4Jeffrey Thompson5John C Adair6Janice E. Knoefel7Gary A. Rosenberg8The Mind Research Network, Albuquerque, NM, United States; Corresponding author.The Mind Research Network, Albuquerque, NM, United States; Department of Radiology, University of Arkansas for Medical Sciences, Little Rock, AR, United StatesDepartment of Neurology, University of New Mexico, Albuquerque, NM, United StatesDepartments of Mathematics and Statistics, University of New Mexico, Albuquerque, NM, United StatesDepartment of Neurology, University of New Mexico, Albuquerque, NM, United StatesDepartment of Neurology, University of New Mexico, Albuquerque, NM, United StatesDepartment of Neurology, University of New Mexico, Albuquerque, NM, United StatesDepartment of Neurology, University of New Mexico, Albuquerque, NM, United StatesDepartment of Neurology, University of New Mexico, Albuquerque, NM, United StatesIntroduction: Subcortical ischemic vascular disease (SIVD) and Alzheimer's disease (AD) related dementia can coexist in older subjects, leading to mixed dementia (MX). Identification of dementia sub-groups is important for designing proper treatment plans and clinical trials. Method: An Alzheimer's disease severity (ADS) score and a vascular disease severity (VDS) score are calculated from CSF and MRI biomarkers, respectively. These scores, being sensitive to different Alzheimer's and vascular disease processes are combined orthogonally in a double-dichotomy plot. This formed an objective basis for clustering the subjects into four groups, consisting of AD, SIVD, MX and leukoaraiosis (LA). The relationship of these four groups is examined with respect to cognitive assessments and clinical diagnosis. Results: Cluster analysis had at least 83% agreement with the clinical diagnosis for groups based either on Alzheimer's or on vascular sensitive biomarkers, and a combined agreement of 68.8% for clustering the four groups. The VDS score was correlated to executive function (r = -0.28, p < 0.01) and the ADS score to memory function (r = −0.35, p < 0.002) after adjusting for age, sex, and education. In the subset of patients for which the cluster scores and clinical diagnoses agreed, the correlations were stronger (VDS score-executive function: r = −0.37, p < 0.006 and ADS score-memory function: r = −0.58, p < 0.0001). Conclusions: The double-dichotomy clustering based on imaging and fluid biomarkers offers an unbiased method for identifying mixed dementia patients and selecting better defined sub-groups. Differential correlations with neuropsychological tests support the hypothesis that the categories of dementia represent different etiologies.http://www.sciencedirect.com/science/article/pii/S2666245021000088Dual pathology dementiaDouble-dichotomy clusteringWhite matterMean diffusivityAmyloidPhosphorylated Tau |
| spellingShingle | Arvind Caprihan Rajikha Raja Laura J. Hillmer Erik Barry Erhardt Jill Prestopnik Jeffrey Thompson John C Adair Janice E. Knoefel Gary A. Rosenberg A double-dichotomy clustering of dual pathology dementia patients Cerebral Circulation - Cognition and Behavior Dual pathology dementia Double-dichotomy clustering White matter Mean diffusivity Amyloid Phosphorylated Tau |
| title | A double-dichotomy clustering of dual pathology dementia patients |
| title_full | A double-dichotomy clustering of dual pathology dementia patients |
| title_fullStr | A double-dichotomy clustering of dual pathology dementia patients |
| title_full_unstemmed | A double-dichotomy clustering of dual pathology dementia patients |
| title_short | A double-dichotomy clustering of dual pathology dementia patients |
| title_sort | double dichotomy clustering of dual pathology dementia patients |
| topic | Dual pathology dementia Double-dichotomy clustering White matter Mean diffusivity Amyloid Phosphorylated Tau |
| url | http://www.sciencedirect.com/science/article/pii/S2666245021000088 |
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