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Biomedical subjects

Eric Reiman

Publications and source records attributed to Eric Reiman.

4 recordsLinked to original sources

X-chromosome-wide association study for Alzheimer's disease.

Due to methodological reasons, the X-chromosome has not been featured in the major genome-wide association studies on Alzheimer's Disease (AD). To address this and better characterize the genetic landscape of AD, we performed an in-depth X-Chromosome-Wide Association Study (XWAS) in 115,841 AD cases or AD proxy cases, including 52,214 clinically-diagnosed AD cases, and 613,671 controls. We considered three approaches to account for the different X-chromosome inactivation (XCI) states in females, i.e. random XCI, skewed XCI, and escape XCI. We did not detect any genome-wide significant signals (P ≤ 5 × 10-8) but identified seven X-chromosome-wide significant loci (P ≤ 1.6 × 10-6). The index variants were common for the Xp22.32, FRMPD4, DMD and Xq25 loci, and rare for the WNK3, PJA1, and DACH2 loci. Overall, this well-powered XWAS found no genetic risk factors for AD on the non-pseudoautosomal region of the X-chromosome, but it identified suggestive signals warranting further investigations.

Humans↗

Apolipoprotein E epsilon 4 affects new learning in cognitively normal individuals at risk for Alzheimer's disease.

The Apolipoprotein E (APOE) epsilon 4 allele is an important risk factor for Alzheimer's disease (AD). Given the interest in early identification of at-risk individuals, we examined memory decline as a function of APOE status and age in cognitively intact participants aged 48-77 years old (yo). Participants were grouped by age (<60 versus > or =60) and APOE (epsilon4+/-). Longitudinal analysis of several components of memory over a 2-year interval showed a significant Age-by-APOE interaction reflecting a decline in new learning for the > or =60 epsilon4+ group only. Among epsilon4+, 76% of the > or =60 participants showed a decline versus 32% of the <60, but the amount of decline in new learning over the 2-year interval within the > or =60 group was not further influenced by age. That is, the size of the 2-year change was the same for 60 and 70 year old participants. This suggests that longitudinal study of new learning is a sensitive measure for detecting early cognitive changes in at-risk individuals that precede the symptomatic onset of mild cognitive impairment and AD.

Aged↗

Clustering huge data sets for parametric PET imaging.

A new preprocessing clustering technique for quantification of kinetic PET data is presented. A two-stage clustering process, which combines a precluster and a classic hierarchical cluster analysis, provides data which are clustered according to a distance measure between time activity curves (TACs). The resulting clustered mean TACs can be used directly for estimation of kinetic parameters at the cluster level, or to span a vector space that is used for subsequent estimation of voxel level kinetics. The introduction of preclustering significantly reduces the overall time for clustering of multiframe kinetic data. The efficiency and superiority of the preclustering scheme combined with thresholding is validated by comparison of the results for clustering both with and without preclustering for FDG-PET brain data of 13 healthy subjects.

Algorithms↗

Neuroimaging and obesity: mapping the brain responses to hunger and satiation in humans using positron emission tomography.

The hypothalamus has a major role in the control of food intake. However, neurotracing studies have shown that the hypothalamus receives input from several other regions of the brain that are likely to modulate its activity. Of particular interest to the understanding of human eating behavior is the possible involvement of the cortex. Using positron emission tomography (PET), we generated functional brain maps of the neuroanatomical correlates of hunger (after a 36-h fast) and satiation (after oral administration of a liquid formula meal) in lean and obese subjects. Results in lean individuals indicate that the neuroanatomical correlates of hunger form a complex network of brain regions including the hypothalamus, thalamus, and several limbic/paralimbic areas such as the insula, hippocampal/parahippocampal formation, and the orbitofrontal cortex. Satiation was associated with preferentially increased neuronal activity in the prefrontal cortex. Our studies also indicate that the brain responses to hunger/satiation in the hypothalamus, limbic/paralimbic areas (commonly associated with the regulation of emotion), and prefrontal cortex (thought to be involved in the inhibition of inappropriate response tendencies) might be different in obese and lean individuals. In conclusion, neuroimaging of the human brain is proving to be an important tool for understanding the complexity of brain involvement in the regulation of eating behavior. PET studies might help to unravel the neuropathophysiology underlying human obesity.

Adolescent↗