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

The behavioral variant of Alzheimer’s disease (bvAD) is characterized by early and predominant behavioral changes, resembling the clinical profile of the behavioral variant of frontotemporal dementia (bvFTD). Social cognition deficits form hallmark features in bvFTD and altered biometric responses to socioemotional cues have been observed in bvFTD. However, little is known about social cognition and its biometric signature in bvAD. In this explorative study, we investigated all levels of social cognition (i.e., level-1: perception, level-2: interpretation and level-3: reasoning), using the Ekman 60 faces test (level-1), Interpersonal Reactivity Index (IRI) and empathy eliciting videos (level-2), the Social Norms Questionnaire (SNQ) and moral dilemmas (level-3), while measuring eyemovements and galvanic skin response (GSR). We compared 12 patients with bvAD with patients with bvFTD (n=14), typical AD (tAD, n=13) and controls (n=15), using ANCOVAs and post hoc testing, adjusting for age and sex. Regarding perception , bvAD (40.1±8.6) showed lower scores on the Ekman test compared to controls (50.1±4.6, p<0.001), and tAD (46.2±5.3, p=0.05) and higher scores compared to bvFTD (32.4±7.3, p=0.002). Eyetracking during the Ekman test revealed that groups did not differ in dwell time on the eyes (all p>0.05), but bvAD (18.7±9.5%) and bvFTD (19.4±14.3%) spent significantly less dwell time on the mouth when viewing the faces than controls (30.4±10.6%, p<0.05) and tAD (32.7±12.1%, p<0.01). Regarding empathy , bvAD (11.3±4.6) exhibited lower scores on the IRI Perspective Taking subscale compared with controls (15±3.4, p=0.02) and similar scores to bvFTD (8.7±5.6, p=0.19) and tAD (13.0±3.2, p=0.43). The GSR to empathy eliciting videos did not differ between groups (all p>0.05). Regarding knowledge of social norms , bvAD (16.0±1.6) and bvFTD (15.2±2.2) showed lower scores on the SNQ than tAD (17.8±2.1, both p<0.05) and controls (18.1±1.3, both p<0.01). Regarding moral reasoning , no differences among the groups were observed in responses to moral dilemmas (all p>0.05), while only bvFTD (0.9±1.1) showed a lower GSR during the personal condition compared with controls (3.2±3.3 peaks per minute, p=0.02). In conclusion, bvAD showed a similar though milder social cognition profile and a similar eyetracking signature compared with bvFTD and greater social cognition impairments and divergent eyemovement patterns compared with tAD. Our results suggest that bvAD and bvFTD show reduced attention to salient features during facial expression perception, potentially contributing to their emotion recognition deficits. These social cognition and biometric measures provide important insights into the basis of behavioral changes in bvAD, and might be valuable for its clinical diagnosis. ### Competing Interest Statement Philip Scheltens has received consultancy fees (paid to the university) from AC Immune, Alzheon, Brainstorm Cell, ImmunoBrain Checkpoint, Novartis, Novo Nordisk. Within his university affiliation he is PI of studies with AC Immune, FUJI-film/Toyama, IONIS, UCB, and Vivoryon. He is otherwise an employee bof Life Sciences Partners Amsterdam. ### Funding Statement Work at the Alzheimer Center Amsterdam was supported by the Netherlands Organisation for Health Research and Development, ZonMw (70-73305-98-1214 to Rik Ossenkoppele, PI) under the BEAT-IT (BEhavioral symptoms in Alzheimer's disease: Towards early Identification and Treatment) study (project #2004404). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics committee/IRB of the Amsterdam University Medical Center gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Data is available upon reasonable request. * Aβ : β amyloid bvAD : behavioral variant of Alzheimer’s disease tAD : typical Alzheimer’s disease bvFTD : behavioral variant frontotemporal dementia MCI : mild cognitive impairment MMSE : mini mental state examination APOE : Apolipoproteine E ADC : Amsterdam Dementia Cohort CSF : cerebrospinal fluid PET : positron emission tomography MRI : magnetic resonance imaging IRI : Interpersonal Reactivity Index SNQ : Social Norms Questionnaire GSR PPM : Galvanic Skin Response Peaks Per Minute AOI : Area of Interest