APOE-Dependent Phenotypes in Subjects with Mild Cognitive Impairment Converting to Alzheimer's Disease

被引：12

作者：

Morgen, Katrin ^{[1
]}

Froelich, Lutz ^{[1
]}

Tost, Heike ^{[1
]}

Plichta, Michael M. ^{[1
]}

Koelsch, Heike ^{[3
]}

Rakebrandt, Fabian ^{[4
]}

Rienhoff, Otto ^{[4
]}

Jessen, Frank ^{[2
,3
]}

Peters, Oliver ^{[5
]}

Jahn, Holger ^{[6
]}

Luckhaus, Christian ^{[7
]}

Huell, Michael ^{[8
]}

Gertz, Hermann-Josef ^{[9
]}

Schroeder, Johannes ^{[10
]}

Hampel, Harald ^{[11
]}

Teipel, Stefan J. ^{[12
,13
]}

Pantel, Johannes ^{[14
]}

Heuser, Isabella ^{[5
]}

Wiltfang, Jens ^{[15
]}

Ruether, Eckart ^{[4
]}

Kornhuber, Johannes ^{[16
]}

Maier, Wolfgang ^{[2
,3
]}

Meyer-Lindenberg, Andreas ^{[1
]}

机构：

[1] Heidelberg Univ, Cent Inst Mental Hlth, Med Fac Mannheim, Mannheim, Germany

[2] German Ctr Neurodegenerat Dis DZNE, Bonn, Germany

[3] Univ Bonn, Dept Psychiat, Bonn, Germany

[4] Univ Hosp Gottingen, Dept Med Informat, Gottingen, Germany

[5] Charite, Dept Psychiat, D-13353 Berlin, Germany

[6] Univ Hosp Hamburg Eppendorf, Dept Psychiat, Hamburg, Germany

[7] Univ Dusseldorf, Dept Psychiat & Psychotherapy, D-40225 Dusseldorf, Germany

[8] Univ Hosp Freiburg, Ctr Geriatr Med & Gerontol Freiburg, Sect Gerontopsychiat & Neuropsychol, Mannheim, Germany

[9] Univ Hosp Leipzig, Dept Psychiat & Psychotherapy, Leipzig, Germany

[10] Heidelberg Univ, Sect Geriatr Psychiat, Heidelberg, Germany

[11] Goethe Univ Frankfurt, Dept Psychiat, D-60054 Frankfurt, Germany

[12] Univ Med Rostock, Rostock, Germany

[13] German Ctr Neurodegenerat Dis, DZNE, Rostock, Germany

[14] Goethe Univ Frankfurt, Inst Gen Practice, D-60054 Frankfurt, Germany

[15] Kliniken Inst Univ Duisburg Essen, Klin Psychiat & Psychotherapie, LVR Kliniken Essen, Essen, Germany

[16] Univ Erlangen Nurnberg, Dept Psychiat & Psychotherapy, D-91054 Erlangen, Germany

来源：

JOURNAL OF ALZHEIMERS DISEASE | 2013年 / 37卷 / 02期

关键词：

APOE; Alzheimer's disease; magnetic resonance imaging; mild cognitive impairment; phenotypes; voxel-based morphometry; VOXEL-BASED MORPHOMETRY; GRAY-MATTER LOSS; APOLIPOPROTEIN-E; BRAIN ATROPHY; BASE-LINE; ASSOCIATION WORKGROUPS; DIAGNOSTIC GUIDELINES; NATIONAL INSTITUTE; MRI; DEMENTIA;

D O I：

10.3233/JAD-130326

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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.

引用

页码：389 / 401

页数：13

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