Differential medial temporal lobe morphometric predictors of item- and relational-encoded memories in healthy individuals and in individuals with mild cognitive impairment and Alzheimer's disease.

INTRODUCTION:Episodic memory processes are supported by different subregions of the medial temporal lobe (MTL). In contrast to a unitary model of memory recognition supported solely by the hippocampus, a current model suggests that item encoding engages perirhinal cortex, whereas relational encoding engages parahippocampal cortex and the hippocampus. However, this model has not been examined in the context of aging, neurodegeneration, and MTL morphometrics. METHODS:Forty-four healthy subjects (HSs) and 18 cognitively impaired subjects (nine mild cognitive impairment [MCI] and nine Alzheimer's disease [AD] patients) were assessed with the relational and item-specific encoding task (RISE) and underwent 3T magnetic resonance imaging. The RISE assessed the differential contribution of relational and item-specific memory. FreeSurfer was used to obtain measures of cortical thickness of MTL regions and hippocampus volume. RESULTS:Memory accuracies for both item and relational memory were significantly better in the HS group than in the MCI/AD group. In MCI/AD group, relational memory was disproportionately impaired. In HSs, hierarchical regressions demonstrated that memory was predicted by perirhinal thickness after item encoding, and by hippocampus volume after relational encoding (both at trend level) and significantly by parahippocampal thickness at associative recognition. The same brain morphometry profiles predicted memory accuracy in MCI/AD, although more robustly perirhinal thickness for item encoding (R2 = 0.31) and hippocampal volume and parahippocampal thickness for relational encoding (R2 = 0.31). DISCUSSION:Our results supported a model of episodic memory in which item-specific encoding was associated with greater perirhinal cortical thickness, while relational encoding was associated with parahippocampal thickness and hippocampus volume. We identified these relationships not only in HSs but also in individuals with MCI and AD. In the subjects with cognitive impairment, reductions in hippocampal volume and impairments in relational memory were especially prominent

Differential medial temporal lobe morphometric predictors of item- and relational-encoded memories in healthy individuals and in individuals with mild cognitive impairment and Alzheimer's disease.

INTRODUCTION:Episodic memory processes are supported by different subregions of the medial temporal lobe (MTL). In contrast to a unitary model of memory recognition supported solely by the hippocampus, a current model suggests that item encoding engages perirhinal cortex, whereas relational encoding engages parahippocampal cortex and the hippocampus. However, this model has not been examined in the context of aging, neurodegeneration, and MTL morphometrics. METHODS:Forty-four healthy subjects (HSs) and 18 cognitively impaired subjects (nine mild cognitive impairment [MCI] and nine Alzheimer's disease [AD] patients) were assessed with the relational and item-specific encoding task (RISE) and underwent 3T magnetic resonance imaging. The RISE assessed the differential contribution of relational and item-specific memory. FreeSurfer was used to obtain measures of cortical thickness of MTL regions and hippocampus volume. RESULTS:Memory accuracies for both item and relational memory were significantly better in the HS group than in the MCI/AD group. In MCI/AD group, relational memory was disproportionately impaired. In HSs, hierarchical regressions demonstrated that memory was predicted by perirhinal thickness after item encoding, and by hippocampus volume after relational encoding (both at trend level) and significantly by parahippocampal thickness at associative recognition. The same brain morphometry profiles predicted memory accuracy in MCI/AD, although more robustly perirhinal thickness for item encoding (R2 = 0.31) and hippocampal volume and parahippocampal thickness for relational encoding (R2 = 0.31). DISCUSSION:Our results supported a model of episodic memory in which item-specific encoding was associated with greater perirhinal cortical thickness, while relational encoding was associated with parahippocampal thickness and hippocampus volume. We identified these relationships not only in HSs but also in individuals with MCI and AD. In the subjects with cognitive impairment, reductions in hippocampal volume and impairments in relational memory were especially prominent

Alpha7 cholinergic-agonist prevents systemic inflammation and improves survival during resuscitation

Severe haemorrhage is a common cause of death despite the recent advances in critical care. Conventional resuscitation fluids are designed to re-establish tissue perfusion, but they fail to prevent inflammatory responses during resuscitation. Our previous studies indicated that the vagus nerve can modulate systemic inflammation via the alpha7 nicotinic acetylcholine receptor (alpha7nAchR). Here, we report that the alpha7nAChR-agonist, GTS, restrains systemic inflammation and improves survival during resuscitation. Resuscitation with GTS rescued all the animals from lethal haemorrhage in a concentration-dependent manner. Unlike conventional resuscitation fluids, GTS inhibited the production of characteristic inflammatory and cardiodepressant factors including tumour necrosis factor (TNF) and high mobility group B protein-1 (HMGB1). Resuscitation with GTS was particularly effective in restraining systemic TNF responses and inhibiting its production in the spleen. At the molecular level, GTS inhibited p65RelA but not RelB NF-kappaB during resuscitation. Unlike non-specific nicotinic agonists, GTS inhibited serum protein TNF levels in both normal and splenectomized, haemorrhagic animals. Resuscitation with GTS inhibited poly(ADP-ribose) polymerase and systemic HMGB1 levels. Our studies suggest that GTS provides significant advantages as compared with non-specific nicotinic agonists, and it could be a promising anti-inflammatory supplement to improve survival during resuscitatio

Extension and refinement of the predictive value of different classes of markers in ADNI: Four-year follow-up data

BACKGROUND: This study examined the predictive value of different classes of markers in the progression from Mild Cognitive Impairment (MCI) to Alzheimer’s disease (AD) over an extended 4 year follow-up in ADNI. METHODS: MCI patients assessed on clinical, cognitive, MRI, PET-FDG, and CSF markers at baseline, and followed on a yearly basis for four years to ascertain progression to AD. Logistic regression models were fitted in clusters including demographics, APOE genotype, cognitive markers, and biomarkers (morphometric, PET-FDG, CSF Abeta and tau). RESULTS: The predictive model at four years revealed that two cognitive measures, an episodic memory measure and a clock drawing screening test, were the best predictors of conversion (AUC= 0.78). CONCLUSIONS: This model of prediction is consistent to the previous model at two years, thus highlighting the importance of cognitive measures in progression from MCI to AD. Cognitive markers were more robust predictors than biomarkers