The relationship of brain amyloid load and APOE status to regional cortical thinning and cognition in the ADNI cohort

Chunfei Li, David Loewenstein, Ranjan Duara, Mercedes Cabrerizo, Warren Barker, Malek Adjouadi

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Background: Both amyloid (Aβ) load and APOE4 allele are associated with neurodegenerative changes in Alzheimer's disease (AD) prone regions and with risk for cognitive impairment. Objective:To evaluate the unique and independent contribution ofAPOE4allele status (E4+\E4-),Aβstatus (Amy+\Amy-), and combined APOE4 and Aβ status on regional cortical thickness (CoTh) and cognition among participants diagnosed as cognitively normal (CN, n = 251), early mild cognitive impairment (EMCI, n = 207), late mild cognitive impairment (LMCI, n = 196), and mild AD (n = 162) from the ADNI. Methods: A series of two-way ANCOVAs with post-hoc Tukey HSD tests, controlling independently for Aβ and APOE4 status and age were examined. Results: Among LMCI and AD participants, cortical thinning was widespread in association with Amy+ status, whereas in association with E4+ status only in the inferior temporal and medial orbito-frontal regions. AmongCNand EMCI participants, E4+ status, but not Amy+ status, was independently associated with increased CoTh, especially in limbic regions [e.g., in the entorhinal cortex, CoTh was 0.123mm greater (p = 0.002) among E4+ than E4- participants]. Among CN and EMCI, both E4+ and Amy+ status were independently associated with cognitive impairment, which was greatest among those with combined E4 + and Amy+ status. Conclusion: Decreased CoTh is independently associated with Amy+ status in many brain regions, but with E4+ status in very restricted number of brain regions. Among CN and EMCI participants, E4 + status is associated with increased CoTh, in medial and inferior temporal regions, although cognitive impairment at this state is independently associated with Amy+ and E4 + status. These findings imply a unique pathophysiological mechanism for E4 + status in AD and its progression.

Original languageEnglish (US)
Pages (from-to)1269-1282
Number of pages14
JournalJournal of Alzheimer's Disease
Volume59
Issue number4
DOIs
StatePublished - 2017

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Keywords

  • ADNI
  • Alzheimer's disease
  • amyloid
  • APOE
  • cortical thinning
  • memory
  • mild cognitive impairment

ASJC Scopus subject areas

  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

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