Dissociating memory networks in early Alzheimer's disease and frontotemporal lobar degeneration - a combined study of hypometabolism and atrophy

PLoS One. 2013;8(2):e55251. doi: 10.1371/journal.pone.0055251. Epub 2013 Feb 14.

Abstract

Introduction: We aimed at dissociating the neural correlates of memory disorders in Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD).

Methods: We included patients with AD (n = 19, 11 female, mean age 61 years) and FTLD (n = 11, 5 female, mean age 61 years) in early stages of their diseases. Memory performance was assessed by means of verbal and visual memory subtests from the Wechsler Memory Scale (WMS-R), including forgetting rates. Brain glucose utilization was measured by [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) and brain atrophy by voxel-based morphometry (VBM) of T1-weighted magnetic resonance imaging (MRI) scans. Using a whole brain approach, correlations between test performance and imaging data were computed separately in each dementia group, including a group of control subjects (n = 13, 6 female, mean age 54 years) in both analyses. The three groups did not differ with respect to education and gender.

Results: Patients in both dementia groups generally performed worse than controls, but AD and FTLD patients did not differ from each other in any of the test parameters. However, memory performance was associated with different brain regions in the patient groups, with respect to both hypometabolism and atrophy: Whereas in AD patients test performance was mainly correlated with changes in the parieto-mesial cortex, performance in FTLD patients was correlated with changes in frontal cortical as well as subcortical regions. There were practically no overlapping regions associated with memory disorders in AD and FTLD as revealed by a conjunction analysis.

Conclusion: Memory test performance may not distinguish between both dementia syndromes. In clinical practice, this may lead to misdiagnosis of FTLD patients with poor memory performance. Nevertheless, memory problems are associated with almost completely different neural correlates in both dementia syndromes. Obviously, memory functions are carried out by distributed networks which break down in brain degeneration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / diagnosis
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology*
  • Alzheimer Disease / physiopathology*
  • Brain / metabolism
  • Brain / pathology*
  • Brain / physiopathology*
  • Female
  • Fluorodeoxyglucose F18
  • Frontotemporal Lobar Degeneration / diagnosis
  • Frontotemporal Lobar Degeneration / metabolism
  • Frontotemporal Lobar Degeneration / pathology*
  • Frontotemporal Lobar Degeneration / physiopathology*
  • Glucose / metabolism
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Memory
  • Middle Aged
  • Positron-Emission Tomography

Substances

  • Fluorodeoxyglucose F18
  • Glucose

Grants and funding

This study has been supported by LIFE - Leipzig Research Center for Civilization Diseases at the University of Leipzig - funded by the European Union, European Regional Development Fund and by the Free State of Saxony within the framework of the excellence initiative (AV, OS and MLS) and by the German Consortium for Frontotemporal Lobar Degeneration, funded by the German Federal Ministry of Education and Research (MLS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.