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 Scopus citations

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 (US)
Pages (from-to)649-660
Number of pages12
JournalBrain Imaging and Behavior
Volume6
Issue number4
DOIs
StatePublished - Nov 20 2012

    Fingerprint

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