Social cognition deficits and biometric signatures in the behavioural variant of Alzheimer’s disease

Abstract

The behavioral variant of Alzheimer’s disease is characterized by early predominant behavioral changes, mimicking the behavioral variant of frontotemporal dementia, which is characterized by social cognition deficits and altered biometric responses to socioemotional cues. These functions remain understudied in the behavioral variant of Alzheimer’s disease. We investigated multiple social cognition components(i.e., emotion recognition, empathy, social norms and moral reasoning), using the Ekman-60-faces-test, Interpersonal-Reactivity-Index, empathy eliciting videos, Social-Norms-Questionnaire and moral dilemmas, while measuring eye-movements and galvanic skin response. We compared 12 patients with the behavioral variant of Alzheimer’s disease with patients with the behavioral variant of frontotemporal dementia(n = 14), typical Alzheimer’s disease(n = 13) and individuals with subjective cognitive decline(n = 13), using ANCOVAs and age and sex adjusted post hoc testing. Patients with the behavioral variant of Alzheimer’s disease(40.1 ± 8.6) showed lower scores on the Ekman-60-faces-test compared to individuals with subjective cognitive decline(49.7 ± 5.0, p < 0.001), and patients with typical Alzheimer’s disease(46.2 ± 5.3, p = 0.05) and higher scores compared to patients with behavioral variant of frontotemporal dementia(32.4 ± 7.3, p = 0.002). Eye-tracking during the Ekman-60-faces-test revealed no differences in dwell time on the eyes(all p > 0.05), but patients with the behavioral variant of Alzheimer’s disease(18.7 ± 9.5%) and frontotemporal dementia(19.4 ± 14.3%) spent significantly less dwell time on the mouth than individuals with subjective cognitive decline(30.7 ± 11.6%, p < 0.01) and patients with typical Alzheimer’s disease(32.7 ± 12.1%, p < 0.01). Patients with the behavioral variant of Alzheimer’s disease(11.3 ± 4.6) exhibited lower scores on the Interpersonal-Reactivity-Index compared with individuals with subjective cognitive decline(15.6 ± 3.1, p = 0.05) and similar scores to patients with the behavioral variant of frontotemporal dementia(8.7 ± 5.6, p = 0.19) and typical Alzheimer’s disease(13.0 ± 3.2, p = 0.43). The galvanic skin response to empathy eliciting videos did not differ between groups(all p > 0.05). Patients with the behavioral variant of Alzheimer’s disease(16.0 ± 1.6) and frontotemporal dementia(15.2 ± 2.2) showed lower scores on the Social-Norms-Questionnaire than patients with typical Alzheimer’s disease(17.8 ± 2.1, p < 0.05) and individuals with subjective cognitive decline(18.3 ± 1.4, p < 0.05). No group differences were observed in scores on moral dilemmas(all p > 0.05), while only patients with the behavioral variant of frontotemporal dementia(0.9 ± 1.1) showed a lower galvanic skin response during personal dilemmas compared with subjective cognitive decline(3.4 ± 3.3 peaks per minute, p = 0.01). Concluding, patients with the behavioral variant of Alzheimer’s disease showed a similar though milder social cognition profile and a similar eye-tracking signature to patients with the behavioral variant of frontotemporal dementia and greater social cognition impairments and divergent eye-movement patterns compared with patients with typical Alzheimer’s disease. Our results suggest reduced attention to salient facial features in these phenotypes, potentially contributing to their emotion recognition deficits.

Decreased emotion recognition and reduced focus on facial hallmarks in behavioral variant frontotemporal dementia compared to primary psychiatric disorders and controls

“…Since the mouth is one of the most prominent features to extract emotions [29], reduced focus on this area may hamper adequate facial expression processing. The result that patients with bvFTD spent less time on the mouth area compared to other diagnostic groups is in line with our previous study, in which part of this bvFTD group was compared with patients with Alzheimer's disease and controls [27]. Reduced focus on facial hallmarks may be related to involvement of the salience network, a brain network that is selectively vulnerable in bvFTD [30].…”

“…A social cognition test battery [27] was presented using a digital platform that integrates social cognitive tests and biometric measures, for example eye tracking technology (iMotions 8.0, iMotions A/S, Frederiksberg, Denmark). Emotion recognition was assessed with the Ekman 60 Faces test [28].…”

The pursuit for markers of disease progression in behavioral variant frontotemporal dementia: a scoping review to optimize outcome measures for clinical trials

“…Novel technologies may improve detection of gradual social cognition decline. Based on the phenomenon of “emotional blunting,” first results on physiological measures (e.g., altered skin conduction or eye gaze) in bvFTD are promising ( Joshi et al, 2014 ; Hutchings et al, 2018 ; Singleton et al, 2022 ). Implementation of biometry might capture objective processes related to social functioning (independent of cognitive or cultural factors), highlighting its potential value as (universal) clinical progression marker.…”

“…While these are promising, at present, literature mostly involves cross-sectional studies in AD. Examples are speech-based artificial intelligence (AI) applications predicting cognitive decline ( Fristed et al, 2022 ), biometric measures (e.g., skin conduction, pupillometry and eye-tracking patterns) reflecting social-emotional and/or linguistic deficits ( Mendez et al, 2018 ; Singleton et al, 2022 ; El Haj et al, 2024 ), AI-based imaging algorithms for longitudinal brain mapping ( Pérez-Millan et al, 2023 ), and proteomics technology detecting protein profiles ( Katzeff et al, 2022 ).…”

Differences and Similarities in Empathy Deficit and Its Neural Basis between Logopenic and Amnesic Alzheimer’s Disease

“…On the other hand, the scores attributed by the informants present the advantage of capturing real-life empathic behavior independently from the patients’ anosognosia [ 10 ]. The last limitation is the absence of healthy controls and the need to use SCD to compare the behavioral data although despite this category of subjects has been already used in previous work exploring empathy in AD [ 69 ].…”