APOE-dependent phenotypes in subjects with mild cognitive impairment converting to Alzheimer's disease

  • Katrin Morgen
  • Lutz Frölich
  • Heike Tost
  • Michael M Plichta
  • Heike Kölsch
  • Fabian Rakebrandt
  • Otto Rienhoff
  • Frank Jessen
  • Oliver Peters
  • Holger Jahn
  • Christian Luckhaus
  • Michael Hüll
  • Hermann-Josef Gertz
  • Johannes Schröder
  • Harald Hampel
  • Stefan J Teipel
  • Johannes Pantel
  • Isabella Heuser
  • Jens Wiltfang
  • Eckart Rüther
  • Johannes Kornhuber
  • Wolfgang Maier
  • Andreas Meyer-Lindenberg

Abstract

BACKGROUND: The E4 isoform of the APOE genotype is the most significant genetic risk factor for sporadic Alzheimer's disease (AD) and has recently been found to modulate disease expression in patients with AD.

OBJECTIVE: To investigate APOE-dependent cognitive and structural phenotypes in subjects with mild cognitive impairment who converted to AD within the following three years.

METHODS: Subjects converting to AD (n = 63) were compared to a control group with stable mild cognitive impairment (n = 131). Clinical, neuropsychological, and MRI data were obtained by the German Dementia Competence Network. Subgroups of converting and stable APOE E4 carriers and non-carriers were investigated longitudinally with MRI to examine structural correlates of conversion. Voxel-based morphometry was applied to investigate gray matter distribution.

RESULTS: At baseline, executive performance correlated with global and bilateral prefrontal gray matter volume and predicted conversion only among non-carriers. Converting carriers and non-carriers presented distinct patterns of brain atrophy on longitudinal analysis, in line with a dissociation between more pronounced occipital atrophy in carriers and more frontoparietal volume loss in non-carriers at follow-up.

CONCLUSIONS: The current findings suggest that in APOE E4 non-carriers with AD, executive dysfunction is closely linked to frontal gray matter atrophy and predictive of progression to dementia. The results are consistent with APOE genotype-dependent profiles of structural damage and cognitive decline in patients with imminent conversion to AD.

Bibliografische Daten

OriginalspracheEnglisch
ISSN1387-2877
DOIs
StatusVeröffentlicht - 01.01.2013
PubMed 23948881