Dysexecutive and amnesic AD subtypes defined by single indicator and modern psychometric approaches: Relationships with SNPs in ADNI

Shubhabrata Mukherjee, Emily Trittschuh, Laura E. Gibbons, R. Scott Mackin, Andrew Saykin, Paul K. Crane

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Previous investigators have suggested the existence of distinct cognitive phenotypes of Alzheimer's disease (AD): a dysexecutive subgroup with executive functioning worse than memory and an amnesic subgroup with memory worse than executive functioning. We evaluated data from the AD Neuroimaging Initiative. We assigned people with AD to dysexecutive and amnesic subgroups using single indicators, and analogously using the ADNI-Mem and ADNI-EF composite scores developed using modern psychometric approaches. We evaluated associations between subgroup membership, APOE genotype, and single nucleotide polymorphisms (SNPs) are associated with AD, and brain vascular disease defined as white matter hyperintensities (WMH) and MRI-identified infarcts. We hypothesized that APOE ε4 and alleles associated with higher risk for AD would predict amnesic subgroup membership; alleles associated with higher WMH or infarct burden would predict dysexecutive subgroup membership. Classification agreement between the two approaches was only fair (kappa = 0. 23). There was no relationship between APOE alleles and the dysexecutive or amnesic phenotypes defined by either categorization approach. There were 58 AD-related and 25 WMH- or infarct-related SNPs for which odds ratios were > 1. 5 or < 0. 67 for dysexecutive vs. amnesic subgroup defined by either categorization approach. Higher proportions of SNPs had odds ratios in the hypothesized direction for the subgroups defined by the modern psychometric approach for AD-related (58 % vs. 38 %, p-value < 0. 001) and brain vascular disease-related SNPs (48 vs. 32 %, p-value = 0. 01). Genetic variation may underlie differential performance in memory and executive functioning among people with AD. Modern psychometric composite scores produced group assignments with more SNP associations in the hypothesized direction.

Original languageEnglish
Pages (from-to)649-660
Number of pages12
JournalBrain Imaging and Behavior
Volume6
Issue number4
DOIs
StatePublished - 2012

Fingerprint

Psychometrics
Single Nucleotide Polymorphism
Alzheimer Disease
Alleles
Brain Diseases
Vascular Diseases
Odds Ratio
Phenotype
Neuroimaging
Genotype
Research Personnel
White Matter

Keywords

  • Alzheimer's disease
  • Executive functioning
  • Genetic analyses
  • Memory
  • Phenotype
  • Psychometrics

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health
  • Neurology
  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience
  • Behavioral Neuroscience
  • Radiology Nuclear Medicine and imaging

Cite this

Dysexecutive and amnesic AD subtypes defined by single indicator and modern psychometric approaches : Relationships with SNPs in ADNI. / Mukherjee, Shubhabrata; Trittschuh, Emily; Gibbons, Laura E.; Mackin, R. Scott; Saykin, Andrew; Crane, Paul K.

In: Brain Imaging and Behavior, Vol. 6, No. 4, 2012, p. 649-660.

Research output: Contribution to journalArticle

Mukherjee, Shubhabrata ; Trittschuh, Emily ; Gibbons, Laura E. ; Mackin, R. Scott ; Saykin, Andrew ; Crane, Paul K. / Dysexecutive and amnesic AD subtypes defined by single indicator and modern psychometric approaches : Relationships with SNPs in ADNI. In: Brain Imaging and Behavior. 2012 ; Vol. 6, No. 4. pp. 649-660.
@article{09dbcfd5ebb94c2f9ad8cac2e635078d,
title = "Dysexecutive and amnesic AD subtypes defined by single indicator and modern psychometric approaches: Relationships with SNPs in ADNI",
abstract = "Previous investigators have suggested the existence of distinct cognitive phenotypes of Alzheimer's disease (AD): a dysexecutive subgroup with executive functioning worse than memory and an amnesic subgroup with memory worse than executive functioning. We evaluated data from the AD Neuroimaging Initiative. We assigned people with AD to dysexecutive and amnesic subgroups using single indicators, and analogously using the ADNI-Mem and ADNI-EF composite scores developed using modern psychometric approaches. We evaluated associations between subgroup membership, APOE genotype, and single nucleotide polymorphisms (SNPs) are associated with AD, and brain vascular disease defined as white matter hyperintensities (WMH) and MRI-identified infarcts. We hypothesized that APOE ε4 and alleles associated with higher risk for AD would predict amnesic subgroup membership; alleles associated with higher WMH or infarct burden would predict dysexecutive subgroup membership. Classification agreement between the two approaches was only fair (kappa = 0. 23). There was no relationship between APOE alleles and the dysexecutive or amnesic phenotypes defined by either categorization approach. There were 58 AD-related and 25 WMH- or infarct-related SNPs for which odds ratios were > 1. 5 or < 0. 67 for dysexecutive vs. amnesic subgroup defined by either categorization approach. Higher proportions of SNPs had odds ratios in the hypothesized direction for the subgroups defined by the modern psychometric approach for AD-related (58 {\%} vs. 38 {\%}, p-value < 0. 001) and brain vascular disease-related SNPs (48 vs. 32 {\%}, p-value = 0. 01). Genetic variation may underlie differential performance in memory and executive functioning among people with AD. Modern psychometric composite scores produced group assignments with more SNP associations in the hypothesized direction.",
keywords = "Alzheimer's disease, Executive functioning, Genetic analyses, Memory, Phenotype, Psychometrics",
author = "Shubhabrata Mukherjee and Emily Trittschuh and Gibbons, {Laura E.} and Mackin, {R. Scott} and Andrew Saykin and Crane, {Paul K.}",
year = "2012",
doi = "10.1007/s11682-012-9207-y",
language = "English",
volume = "6",
pages = "649--660",
journal = "Brain Imaging and Behavior",
issn = "1931-7557",
publisher = "Springer New York",
number = "4",

}

TY - JOUR

T1 - Dysexecutive and amnesic AD subtypes defined by single indicator and modern psychometric approaches

T2 - Relationships with SNPs in ADNI

AU - Mukherjee, Shubhabrata

AU - Trittschuh, Emily

AU - Gibbons, Laura E.

AU - Mackin, R. Scott

AU - Saykin, Andrew

AU - Crane, Paul K.

PY - 2012

Y1 - 2012

N2 - Previous investigators have suggested the existence of distinct cognitive phenotypes of Alzheimer's disease (AD): a dysexecutive subgroup with executive functioning worse than memory and an amnesic subgroup with memory worse than executive functioning. We evaluated data from the AD Neuroimaging Initiative. We assigned people with AD to dysexecutive and amnesic subgroups using single indicators, and analogously using the ADNI-Mem and ADNI-EF composite scores developed using modern psychometric approaches. We evaluated associations between subgroup membership, APOE genotype, and single nucleotide polymorphisms (SNPs) are associated with AD, and brain vascular disease defined as white matter hyperintensities (WMH) and MRI-identified infarcts. We hypothesized that APOE ε4 and alleles associated with higher risk for AD would predict amnesic subgroup membership; alleles associated with higher WMH or infarct burden would predict dysexecutive subgroup membership. Classification agreement between the two approaches was only fair (kappa = 0. 23). There was no relationship between APOE alleles and the dysexecutive or amnesic phenotypes defined by either categorization approach. There were 58 AD-related and 25 WMH- or infarct-related SNPs for which odds ratios were > 1. 5 or < 0. 67 for dysexecutive vs. amnesic subgroup defined by either categorization approach. Higher proportions of SNPs had odds ratios in the hypothesized direction for the subgroups defined by the modern psychometric approach for AD-related (58 % vs. 38 %, p-value < 0. 001) and brain vascular disease-related SNPs (48 vs. 32 %, p-value = 0. 01). Genetic variation may underlie differential performance in memory and executive functioning among people with AD. Modern psychometric composite scores produced group assignments with more SNP associations in the hypothesized direction.

AB - Previous investigators have suggested the existence of distinct cognitive phenotypes of Alzheimer's disease (AD): a dysexecutive subgroup with executive functioning worse than memory and an amnesic subgroup with memory worse than executive functioning. We evaluated data from the AD Neuroimaging Initiative. We assigned people with AD to dysexecutive and amnesic subgroups using single indicators, and analogously using the ADNI-Mem and ADNI-EF composite scores developed using modern psychometric approaches. We evaluated associations between subgroup membership, APOE genotype, and single nucleotide polymorphisms (SNPs) are associated with AD, and brain vascular disease defined as white matter hyperintensities (WMH) and MRI-identified infarcts. We hypothesized that APOE ε4 and alleles associated with higher risk for AD would predict amnesic subgroup membership; alleles associated with higher WMH or infarct burden would predict dysexecutive subgroup membership. Classification agreement between the two approaches was only fair (kappa = 0. 23). There was no relationship between APOE alleles and the dysexecutive or amnesic phenotypes defined by either categorization approach. There were 58 AD-related and 25 WMH- or infarct-related SNPs for which odds ratios were > 1. 5 or < 0. 67 for dysexecutive vs. amnesic subgroup defined by either categorization approach. Higher proportions of SNPs had odds ratios in the hypothesized direction for the subgroups defined by the modern psychometric approach for AD-related (58 % vs. 38 %, p-value < 0. 001) and brain vascular disease-related SNPs (48 vs. 32 %, p-value = 0. 01). Genetic variation may underlie differential performance in memory and executive functioning among people with AD. Modern psychometric composite scores produced group assignments with more SNP associations in the hypothesized direction.

KW - Alzheimer's disease

KW - Executive functioning

KW - Genetic analyses

KW - Memory

KW - Phenotype

KW - Psychometrics

UR - http://www.scopus.com/inward/record.url?scp=84871714261&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84871714261&partnerID=8YFLogxK

U2 - 10.1007/s11682-012-9207-y

DO - 10.1007/s11682-012-9207-y

M3 - Article

C2 - 23161456

AN - SCOPUS:84871714261

VL - 6

SP - 649

EP - 660

JO - Brain Imaging and Behavior

JF - Brain Imaging and Behavior

SN - 1931-7557

IS - 4

ER -