Longitudinal multivariate normative comparisons

Neuropsychology Working Group of the MACS

Research output: Contribution to journalArticlepeer-review


Motivated by the Multicenter AIDS Cohort Study (MACS), we develop classification procedures for cognitive impairment based on longitudinal measures. To control family-wise error, we adapt the cross-sectional multivariate normative comparisons (MNC) method to the longitudinal setting. The cross-sectional MNC was proposed to control family-wise error by measuring the distance between multiple domain scores of a participant and the norms of healthy controls and specifically accounting for intercorrelations among all domain scores. However, in a longitudinal setting where domain scores are recorded multiple times, applying the cross-sectional MNC at each visit will still have inflated family-wise error rate due to multiple testing over repeated visits. Thus, we propose longitudinal MNC procedures that are constructed based on multivariate mixed effects models. A (Formula presented.) test procedure is adapted from the cross-sectional MNC to classify impairment on longitudinal multivariate normal data. Meanwhile, a permutation procedure is proposed to handle skewed data. Through simulations we show that our methods can effectively control family-wise error at a predetermined level. A dataset from a neuropsychological substudy of the MACS is used to illustrate the applications of our proposed classification procedures.

Original languageEnglish (US)
Pages (from-to)1440-1452
Number of pages13
JournalStatistics in Medicine
Issue number6
StatePublished - Mar 15 2021


  • cognitive impairment
  • false discovery rate
  • family-wise error rate
  • longitudinal analysis
  • multivariate mixed-effect model

ASJC Scopus subject areas

  • Epidemiology
  • Statistics and Probability


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