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.
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.
Authors: Piotr Lewczuk; Peter Riederer; Sid E O'Bryant; Marcel M Verbeek; Bruno Dubois; Pieter Jelle Visser; Kurt A Jellinger; Sebastiaan Engelborghs; Alfredo Ramirez; Lucilla Parnetti; Clifford R Jack; Charlotte E Teunissen; Harald Hampel; Alberto Lleó; Frank Jessen; Lidia Glodzik; Mony J de Leon; Anne M Fagan; José Luis Molinuevo; Willemijn J Jansen; Bengt Winblad; Leslie M Shaw; Ulf Andreasson; Markus Otto; Brit Mollenhauer; Jens Wiltfang; Martin R Turner; Inga Zerr; Ron Handels; Alexander G Thompson; Gunilla Johansson; Natalia Ermann; John Q Trojanowski; Ilker Karaca; Holger Wagner; Patrick Oeckl; Linda van Waalwijk van Doorn; Maria Bjerke; Dimitrios Kapogiannis; H Bea Kuiperij; Lucia Farotti; Yi Li; Brian A Gordon; Stéphane Epelbaum; Stephanie J B Vos; Catharina J M Klijn; William E Van Nostrand; Carolina Minguillon; Matthias Schmitz; Carla Gallo; Andrea Lopez Mato; Florence Thibaut; Simone Lista; Daniel Alcolea; Henrik Zetterberg; Kaj Blennow; Johannes Kornhuber Journal: World J Biol Psychiatry Date: 2017-10-27 Impact factor: 4.132
Authors: Katrin Morgen; Michael Schneider; 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 Journal: Alzheimers Res Ther Date: 2015-05-15 Impact factor: 6.982