APOE-Dependent Phenotypes in Subjects with Mild Cognitive Impairment Converting to Alzheimer%26apos;s Disease

作者：Morgen Katrin^*; Froelich Lutz; Tost Heike; Plichta Michael M; Koelsch Heike; Rakebrandt Fabian; Rienhoff Otto; Jessen Frank; Peters Oliver; Jahn Holger; Luckhaus Christian; Huell Michael; Gertz Hermann Josef; Schroeder Johannes; Hampel Harald; Teipel Stefan J; Pantel Johannes; Heuser Isabella; Wiltfang Jens; Ruether Eckart; Kornhuber Johannes; Maier Wolfgang; Meyer Lindenberg Andreas

来源：Journal of Alzheimer's Disease, 2013, 37(2): 389-401.

DOI：10.3233/JAD-130326

• APOE
• Alzheimer%26apos
• s disease
• magnetic resonance imaging
• mild cognitive impairment
• phenotypes
• voxel-based morphometry

Background: The E4 isoform of the APOE genotype is the most significant genetic risk factor for sporadic Alzheimer%26apos;s disease (AD) and has recently been found to modulate disease expression in patients with AD. %26lt;br%26gt;Objective: To investigate APOE-dependent cognitive and structural phenotypes in subjects with mild cognitive impairment who converted to AD within the following three years. %26lt;br%26gt;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. %26lt;br%26gt;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. %26lt;br%26gt;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.

• 出版日期2013
• 单位上海市精神卫生中心