Functional reorganization of memory processing in the hippocampus is associated with neuroprotector GLP-1 levels in type 2 diabetes.

Type 2 diabetes (T2D) often impairs memory functions, suggesting specific vulnerability of the hippocampus. In vivo neuroimaging studies relating encoding and retrieval of memory information with endogenous neuroprotection are lacking. The neuroprotector glucagon-like peptide (GLP-1) has a high receptor density in anterior/ventral hippocampus, as shown by animal models. Using an innovative event-related fMRI design in 34 participants we investigated patterns of hippocampal activity in T2D (n = 17) without mild cognitive impairment (MCI) versus healthy controls (n = 17) during an episodic memory task. We directly measured neurovascular coupling by estimating the hemodynamic response function using event-related analysis related to encoding and retrieval of episodic information in the hippocampus. We applied a mixed-effects general linear model analysis and a two-factor ANOVA to test for group differences. Significant between-group differences were found for memory encoding, showing evidence for functional reorganization: T2D patients showed an augmented activation in the posterior hippocampus while anterior activation was reduced. The latter was negatively correlated with both GLP-1 pre- and post-breakfast levels, in the absence of grey matter changes. These results suggest that patients with T2D without MCI have pre-symptomatic functional reorganization in brain regions underlying episodic memory, as a function of the concentration of the neuroprotective neuropeptide GLP-1.

Hemispheric Patterns of Recruitment of Object Processing Regions in Early Alzheimer's Disease: A Study Along the Entire Ventral Stream.

BACKGROUND: Investigation of neural response patterns along the entire network of functionally defined object recognition ventral stream regions in Alzheimer's disease (AD) is surprisingly lacking. OBJECTIVE: We aimed to investigate putative functional reorganization along a wide-ranging network of known regions in the ventral visual stream in mild AD. METHODS: Overall we investigated 6 regions of interest (5 of which were not investigated before), in 19 AD patients and 19 controls, in both hemispheres along the ventral visual stream: Fusiform Face Area, Fusiform Body Area, Extrastriate Body Area, Lateral Occipital Cortex, Parahippocampal Place Area, and Visual Word Form Area, while assessing object recognition performance. RESULTS: We found group differences in dprime measures for all object categories, corroborating generalized deficits in object recognition. Concerning neural responses, we found region dependent group differences respecting a priori expected Hemispheric asymmetries. Patients showed significantly decreased BOLD responses in the right hemisphere-biased Fusiform Body Area, and lower left hemisphere responses in the Visual Word Form Area (with a priori known left hemispheric bias), consistent with deficits in body shape and word/pseudoword processing deficits. This hemispheric dominance related effects were preserved when controlling for performance differences. Whole brain analysis during the recognition task showed enhanced activity in AD group of left dorsolateral prefrontal cortex, left cingulate gyrus, and in the posterior cingulate cortex- a hotspot of amyloid-ß accumulation. CONCLUSION: These findings demonstrate region dependent respecting hemispheric dominance patterns activation changes in independently localized selective regions in mild AD, accompanied by putative compensatory activity of frontal and cingular networks.