Lateral Temporal Lobe: An Early Imaging Marker of the Presymptomatic GRN Disease?

J Alzheimers Dis. 2015;47(3):751-9. doi: 10.3233/JAD-150270.

Abstract

The preclinical stage of frontotemporal lobar degeneration (FTLD) is not well characterized. We conducted a brain metabolism (FDG-PET) and structural (cortical thickness) study to detect early changes in asymptomatic GRN mutation carriers (aGRN+) that were evaluated longitudinally over a 20-month period. At baseline, a left lateral temporal lobe hypometabolism was present in aGRN+ without any structural changes. Importantly, this is the first longitudinal study and, across time, the metabolism more rapidly decreased in aGRN+ in lateral temporal and frontal regions. The main structural change observed in the longitudinal study was a reduction of cortical thickness in the left lateral temporal lobe in carriers. A limit of this study is the relatively small sample (n = 16); nevertheless, it provides important results. First, it evidences that the pathological processes develop a long time before clinical onset, and that early neuroimaging changes might be detected approximately 20 years before the clinical onset of disease. Second, it suggests that metabolic changes are detectable before structural modifications and cognitive deficits. Third, both the baseline and longitudinal studies provide converging results implicating lateral temporal lobe as early involved in GRN disease. Finally, our study demonstrates that structural and metabolic changes could represent possible biomarkers to monitor the progression of disease in the presymptomatic stage toward clinical onset.

Keywords: Cortical thickness; GRN; PET; dementia; frontotemporal dementia; frontotemporal lobar degeneration; longitudinal; preclinical study; presymptomatic; progranulin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Asymptomatic Diseases
  • Disease Progression
  • Female
  • Fluorodeoxyglucose F18
  • Frontal Lobe / metabolism
  • Frontal Lobe / pathology
  • Frontotemporal Lobar Degeneration / diagnosis
  • Frontotemporal Lobar Degeneration / genetics
  • Frontotemporal Lobar Degeneration / metabolism*
  • Frontotemporal Lobar Degeneration / pathology*
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Longitudinal Studies
  • Magnetic Resonance Imaging
  • Male
  • Mutation*
  • Organ Size
  • Positron-Emission Tomography
  • Progranulins
  • Radiopharmaceuticals
  • Temporal Lobe / diagnostic imaging
  • Temporal Lobe / metabolism*
  • Temporal Lobe / pathology*

Substances

  • GRN protein, human
  • Intercellular Signaling Peptides and Proteins
  • Progranulins
  • Radiopharmaceuticals
  • Fluorodeoxyglucose F18