Neural correlates of empathy in mild cognitive impairment.

The occurrence of clinically significant changes in empathy is a matter of debate in Alzheimer's disease (AD). Altered empathic mechanisms observed in AD may be a consequence of cognitive impairment, more specifically of reduced mental flexibility and self-regulation. The present study explored possible changes in empathy for subjects in the prodromal phase of AD, namely mild cognitive impairment (MCI) due to AD, and of their neural substrates. Eighteen MCI patients and 20 healthy controls (HC) were included in the study. The Interpersonal Reactivity Index (IRI) questionnaire was administered to each participant. The IRI encompasses four factors: Perspective Taking; Fantasy; Empathic Concern; Personal Distress. MCI patients underwent a magnetic resonance imaging structural examination and were compared to 30 healthy controls (HC-MRI). A limited number of cortical and subcortical regions involved in social cognition was selected as regions of interest (ROIs). MCI individuals obtained lower scores than HC in the Perspective Taking and Fantasy subscales of the IRI, whereas they obtained higher scores on Empathic Concern. Regarding neuroimaging data, a significant correlation emerged between IRI scores and the neural measurements of different regions involved in empathy, especially covering the temporoparietal junction, which is a critical region engaged in both affective and cognitive dimensions of empathy. The results of the present study suggest that a subtle impairment in regulatory mechanisms of empathy may occur very early during the course of AD, possibly as a consequence of neuropathological changes occurring in brain regions involved in social cognition.

Blood-brain barrier permeability is associated with different neuroinflammatory profiles in Alzheimer's disease.

INTRODUCTION: Inflammation is an important player in Alzheimer's disease (AD), whose effects can be influenced by the blood-brain barrier (BBB). Here, we investigated the relationship between BBB permeability, indicated by cerebrospinal fluid (CSF)/plasma albumin quotient (Qalb), and CSF indexes of neuroinflammation in a cohort of biologically defined AD patients. METHODS: Fifty-nine consecutive patients with mild cognitive impairment (MCI) or early AD (Mini-Mental State Examination [MMSE] >22) underwent CSF analysis for inflammatory cytokines (interleukin [IL]-1ß, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, Il-10, IL-12, IL-13, IL-17, tumor necrosis factor-α [TNF-α], interferon-γ [IFN-γ], granulocyte-monocyte colony-stimulating factor [GM-CSF], granulocyte colony-stimulating factor [G-CSF]). Using backward stepwise linear regression analysis, we explored the potential influence of each cytokine CSF level on Qalb considering age, sex, and apolipoprotein E (APOE) as covariates. RESULTS: Higher levels of IL-4 (ß = 0.356, 0.005) and IL-8 (ß = 0.249, 0.05) were associated with higher Qalb values, while macrophage inflammatory protein-1α (MIP-1ß) (ß = -0.274; p = 0.032) and TNF-α (ß = -0.248; p = 0.031) showed a significant negative association with BBB permeability. Age was also positively associated with Qalb (ß = 0.283; p = 0.016). CONCLUSIONS: Despite the overall integrity of the BBB, its permeability could either influence or be influenced by central neuroinflammation, reflected by CSF cytokine levels. This is in line with previous studies that showed that patients with a more intact barrier are those with more prominent neurodegeneration. Our findings suggest that different neuroinflammatory profiles can be associated with different levels of BBB permeability in AD.