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Longitudinal changes in medial temporal cortical thickness in normal subjects with the APOE-4 polymorphism

David Geffen School of Medicine at UCLA, Center for Cognitive Neurosciences, Semel Institute, Los Angeles, CA 90095, USA.
NeuroImage (Impact Factor: 6.36). 10/2010; 53(1):37-43. DOI: 10.1016/j.neuroimage.2010.06.009
Source: PubMed

ABSTRACT People with the apolipoprotein-Eepsilon4 (APOE-4) genetic risk for Alzheimer's disease show morphologic differences in medial temporal lobe regions when compared to non-carriers of the allele. Using a high-resolution MRI and cortical unfolding approach, our aim was to determine the rate of cortical thinning among medial temporal lobe subregions over the course of 2 years. We hypothesized that APOE-4 genetic risk would contribute to longitudinal cortical thickness change in the subiculum and entorhinal cortex, regions preferentially susceptible to Alzheimer's disease related pathology. Thirty-two cognitively intact subjects, mean age 61 years, 16 APOE-4 carriers, 16 non-carriers, underwent baseline and follow-up MRI scans. Over this relatively brief interval, we found significantly greater cortical thinning in the subiculum and entorhinal cortex of APOE-4 carriers when compared to non-carriers of the allele. Average cortical thinning across all medial temporal lobe subregions combined was also significantly greater for APOE-4 carriers. This finding is consistent with the hypothesis that carrying the APOE-4 allele renders subjects at a higher risk for developing Alzheimer's disease.

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    • "The ApoE-E4 allele is the major genetic risk factor for late-onset AD [Corder et al., 1993; Farrer et al., 1997]. Some cross-sectional studies have reported smaller MRI volumes and greater rates of atrophy of MTL structures among cognitively normal ApoE-E4 carriers than in E4 non-carriers [Burggren et al., 2008; Chiang et al., 2011; Cohen et al., 2001; Donix et al., 2010; Honea et al., 2009; Lu et al., 2011]. However, these studies did not include long-term clinical follow-up and diagnostic outcomes that are necessary for determining whether these changes were related to the subsequent diagnosis of MCI. "
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    ABSTRACT: This study evaluated the utility of baseline and longitudinal magnetic resonance imaging (MRI) measures of medial temporal lobe brain regions collected when participants were cognitively normal and largely in middle age (mean age 57 years) to predict the time to onset of clinical symptoms associated with mild cognitive impairment (MCI). Furthermore, we examined whether the relationship between MRI measures and clinical symptom onset was modified by apolipoprotein E (ApoE) genotype and level of cognitive reserve (CR). MRI scans and measures of CR were obtained at baseline from 245 participants who had been followed for up to 18 years (mean follow-up 11 years). A composite score based on reading, vocabulary, and years of education was used as an index of CR. Cox regression models showed that lower baseline volume of the right hippocampus and smaller baseline thickness of the right entorhinal cortex predicted the time to symptom onset independently of CR and ApoE-ɛ4 genotype, which also predicted the onset of symptoms. The atrophy rates of bilateral entorhinal cortex and amygdala volumes were also associated with time to symptom onset, independent of CR, ApoE genotype, and baseline volume. Only one measure, the left entorhinal cortex baseline volume, interacted with CR, such that smaller volumes predicted symptom onset only in individuals with lower CR. These results suggest that MRI measures of medial temporal atrophy, ApoE-ɛ4 genotype, and the protective effects of higher CR all predict the time to onset of symptoms associated with MCI in a largely independent, additive manner during the preclinical phase of Alzheimer's disease. Hum Brain Mapp, 2015. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
    Human Brain Mapping 04/2015; 36(7). DOI:10.1002/hbm.22810 · 6.92 Impact Factor
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    • "Regarding longitudinal MRI studies, results in elderly are more consistent. Most studies highlighted a faster rate of grey matter atrophy in APOE4 carriers compared with non-carriers, especially in medial temporal structures (Cohen et al. 2001; Chen et al. 2007; Morra et al. 2009; Donix et al. 2010a; Hua et al. 2010; Risacher et al. 2010; Chiang et al. 2011; Lu et al. 2011; Roussotte et al. 2014), although negative findings have also been reported (Jack et al. 1998; Du et al. 2006; Schuff et al. 2009; Taylor et al. 2014). In contrast, normal elderly APOE2 carriers showed a slower rate of hippocampal grey matter atrophy compared with APOE3 homozygotes (Chiang et al. 2011). "
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    • "It is one of the first structures to exhibit neurofibrillary tangles in AD, and exhibits massive neuronal loss in superficial layers as the disease progresses (Van Hoesen et al. 1991; Braak and Braak 1995; Gomez-Isla et al. 1996). Interestingly, EC cortical volume and subregional thickness are reduced in cognitively normal APOE-14 carriers (Shaw et al. 2007; Burggren et al. 2008; Donix et al. 2010), suggesting an early manifestation of cortico-hippocampal dysfunction in prodromal AD. Analyses of Golgi-stained MEC neurons by dendritic compartment reveal that reductions in total dendritic length and spine density of E4 "
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