Presymptomatic cognitive decline in familial frontotemporal dementia: A longitudinal study

Neurology. 2016 Jul 26;87(4):384-91. doi: 10.1212/WNL.0000000000002895. Epub 2016 Jun 29.

Abstract

Objective: In this prospective cohort study, we performed a 2-year follow-up study with neuropsychological assessment in the presymptomatic phase of familial frontotemporal dementia (FTD) due to GRN and MAPT mutations to explore the prognostic value of neuropsychological assessment in the earliest FTD disease stages.

Methods: Healthy, at-risk, first-degree relatives of patients with FTD who had a MAPT (n = 13) or GRN mutation (n = 30) and healthy controls (n = 39) underwent neuropsychological assessment at baseline and 2-year follow-up. We investigated baseline and longitudinal differences, as well as relationship with age and estimated years before symptom onset.

Results: At baseline, GRN mutation carriers showed lower scores on mental processing speed than healthy controls (p = 0.043). Two years later, MAPT mutation carriers showed a steeper decline than GRN mutation carriers on social cognition (p = 0.002). Older age was related to cognitive decline in visuoconstruction (p = 0.005) and social cognition (p = 0.026) in MAPT. Memory significantly declined from 8 to 6 years before estimated symptom onset in MAPT and GRN mutation carriers, respectively, and language and social cognition declined only in MAPT mutation carriers from 7 to 5 years before estimated symptom onset, respectively (p < 0.05).

Conclusions: Using longitudinal neuropsychological assessment, we detected gene-specific neuropsychological patterns of decline in, e.g., social cognition, memory, and visuoconstruction. Our results confirm the prognostic value of neuropsychological assessment as a potential clinical biomarker in the presymptomatic phase of familial FTD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age of Onset
  • Aging / psychology
  • Cognition Disorders / etiology*
  • Cognition Disorders / psychology*
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Frontotemporal Dementia / complications*
  • Frontotemporal Dementia / genetics
  • Frontotemporal Dementia / psychology*
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Mutation
  • Neuropsychological Tests
  • Progranulins
  • Prospective Studies
  • Social Behavior
  • tau Proteins / genetics

Substances

  • GRN protein, human
  • Intercellular Signaling Peptides and Proteins
  • MAPT protein, human
  • Progranulins
  • tau Proteins