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

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

Stefan Frisch  1 , Juergen Dukart, Barbara Vogt, Annette Horstmann, Georg Becker, Arno Villringer, Henryk Barthel, Osama Sabri, Karsten Müller, Matthias L Schroeter
Affiliations

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

Stefan Frisch et al. PLoS One. 2013.

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.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Group differences.
Differences between AD patients and controls (upper part) as well as FTLD patients versus controls (lower part) in brain glucose utilization (FDG-PET, red) and atrophy (MRI, blue). Areas of overlap are shown in violet. Only clusters are shown that exceeded a significance threshold of p<0.001 uncorrected at voxel level and a cluster threshold of 2000 voxels. Left is left.
Figure 2
Figure 2. Memory performance and hypometabolism.
Correlations between hypometabolism (FDG-PET) and each memory measure for AD patients and controls (blue) as well as FTLD patients and controls (red). LM: WMS Logical Memory, VR: WMS Visual Reproduction, 1: immediate recall, 2: delayed recall, FR: Forgetting rate. Results are only reported for those memory measures for which significant correlations in any region were found. Only clusters are shown that exceeded a significance threshold of p<0.001 uncorrected at voxel level and a cluster threshold of 2000 voxels. Left is left.
Figure 3
Figure 3. Memory performance and atrophy.
Correlations between atrophy (MRI) and each memory measure for AD patients and controls (blue) as well as FTLD patients and controls (red). Areas of overlap are shown in violet (in LM1 only). LM: WMS Logical Memory, VR: WMS Visual Reproduction, 1: immediate recall, 2: delayed recall, FR: Forgetting rate. Results are only reported for those memory measures for which significant correlations in any region were found. Only clusters are shown that exceeded a significance threshold of p<0.001 uncorrected at voxel level and a cluster threshold of 2000 voxels. Left is left.
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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.