Social cognition, essential for interpreting and responding to social contexts, is frequently impaired in neurological and psychiatric disorders. Multiple brain regions, organized in large-scale brain networks, represent the neurobiological substrate of social cognitive abilities, and are the main target of neurodegeneration in the fronto-temporal dementia spectrum. The focus of this review is a specific anatomic subcomponent of these networks, i.e. the amygdalo-hippocampal complex (AHC). Animal models suggest that the AHC is involved in processes underlying social cognition through both localized mechanisms and integration within large-scale networks. In humans, AHC pathology in conditions such as Alzheimer’s disease (AD), epilepsy, and autoimmune encephalitis (AIE) has been associated with social cognition impairment. In AD and Mild Cognitive Impairment (MCI) deficits in Theory of Mind (ToM), empathy, and emotion recognition are common and linked to medial temporal atrophy. In focal frontal and temporal lobe epilepsy, seizures and interictal dysfunctions disrupt social cognition, particularly ToM, from early stages. In AIE, marked fear recognition deficits are closely related to amygdala involvement. These conditions highlight the association between social cognition impairments and damage to the AHC. From a theoretical perspective, investigating the relationship between the AHC and social cognition may advance our understanding of the neurobiological underpinnings of social behavior. Clinically, the systematic assessment of social cognition in patients with conditions affecting the AHC appears warranted, potentially improving diagnosis, prognostic evaluation, and therapeutic strategies.
BACKGROUND
Currently, no single biomarker can reliably identify preclinical Alzheimer's disease (AD), particularly at or before the mild cognitive impairment (MCI) stage. Given the heterogeneity of MCI, integrative approaches are needed to improve early risk stratification.
OBJECTIVES
(i) To derive robust latent cognitive components from a multicenter, clinically defined MCI cohort using principal component analysis (PCA); (ii) to investigate the associations between these components and plasma p-tau217 and p-tau181 levels.
METHODS
Data from 742 MCI participants in the AI-Mind cohort were analyzed. Cognitive domains were derived using PCA with varimax rotation and tested for associations with plasma p-tau biomarkers using site-specific linear regressions, adjusted for age, sex, and education.
RESULTS
A reproducible four-component cognitive structure emerged (memory, executive/processing speed, verbal fluency, visuospatial ability), with memory as the most p-tau-sensitive domain. The p-tau217 measure showed stronger associations with memory than p-tau181, though effects varied by site.
CONCLUSION
The findings indicate that a robust four-factor cognitive structure can be identified in clinically defined MCI cohorts without prior biological selection. The association between latent memory factors and plasma p-tau217, observed primarily in cohorts with higher biomarker burden or clearer amnestic profiles, highlights the potential for blood-based biomarkers to refine risk assessment in routine clinical practice.
Ana S. Perez, Hugo L. Hammer, V. Andersson et al.· GeroScience· 0 citations
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