Longitudinal Neuropsychological Study of Presymptomatic c.709-1G>A Progranulin Mutation Carriers

J Int Neuropsychol Soc. 2019 Jan;25(1):39-47. doi: 10.1017/S1355617718000735. Epub 2018 Oct 29.

Abstract

Objective: The assessment of individuals from families affected by familial frontotemporal dementia (FTD) allows the evaluation of preclinical or pre-diagnosis disease markers. The current work aims to investigate the existence of a cognitive phase in GRN mutation carriers before overt clinical symptoms begin.

Methods: We performed a longitudinal neuropsychological analysis (three assessments in 4 years) in a group of presymptomatic c.709-1G>A progranulin (GRN) (n=15) mutation carriers and non-carrier relatives (n=25) from seven FTD families.

Results: GRN mutation carriers showed subtle decline over the longitudinal follow-up in several different domains (namely, attention, facial affect recognition, decision-making, language, and memory). The differences between groups were most marked in the facial affect recognition test, with improvement in the non-carrier group and decline in the GRN mutation carrier group, with very large effect sizes.

Conclusions: Facial affect recognition may decline before clinical diagnosis and makes the adapted version of the Picture of Facial Affect a potential candidate for early detection of GRN-associated FTD. (JINS, 2019, 25, 39-47).

Keywords: Asymptomatic diseases; Frontotemporal dementia; Frontotemporal lobar degeneration; Longitudinal studies; Neuropsychological tests; human; progranulin protein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Affect / physiology*
  • Aged
  • Biomarkers
  • Cognitive Dysfunction* / diagnosis
  • Cognitive Dysfunction* / genetics
  • Cognitive Dysfunction* / physiopathology
  • Facial Expression*
  • Facial Recognition / physiology*
  • Female
  • Frontotemporal Dementia* / diagnosis
  • Frontotemporal Dementia* / genetics
  • Frontotemporal Dementia* / physiopathology
  • Heterozygote
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Progranulins / genetics*

Substances

  • Biomarkers
  • GRN protein, human
  • Progranulins