Biobehavioral synchrony between three to four months old infants and psychologically healthy mothers during the face-to-face still-face paradigm.

Under the ATN framework, individuals who are positive for both amyloid beta (Aβ+) and tau (T+) pathology meet the criteria for Alzheimer's disease (AD) classification, irrespective of cognitive status. Despite the required presence of both pathologies, neocortical (NEO) tau density in particular is linked most strongly to cognitive decline., Early tau accumulation in the medial temporal lobe (MTL), in particular the entorhinal cortex, is an early precursor to rapid tau proliferation into the neocortex in preclinical AD. The transition from MTL to NEO tau is not inevitable; while the presence of Aβ and higher MTL tau burden accelerates this “caTAUstrophe”,, considerable heterogeneity exists in the extent to which an Aβ+ individual might progress to NEO T+. This variability raises an important question: Why do some Aβ+ individuals, who may also possess other risk factors including older age, apolipoprotein E () ε4 carriership, or female sex, remain low in NEO tau burden (i.e., reflecting NEO tau resistance), while others predictably follow this path? Female sex in particular presents a compelling factor potentially modulating resistance to NEO tau burden, given well‐established sex differences showing higher MTL and NEO tau levels in women, faster rates of tau accumulation and proliferation, and reduced overall brain resilience to tau pathology compared to men. Therefore, the current study aimed to investigate whether and how resistance to NEO tau burden presented differently in men and women. Among Aβ+ older adults from three cohorts, we separately estimated male and female NEO tau resistance using the recently published inverse learning approach. Sex‐specific models were built to estimate NEO tau resistance. We first examined how resistance presented in women and men separately (i.e., “what is resistance”) by looking at our expectation models themselves. Subsequently, using our models to estimate resistance in women and men, we tested which factors associated with NEO tau resistance in each sex. A total of  = 872 Aβ+ individuals across the AD continuum were selected from the Anti‐Amyloid Treatment in Asymptomatic Alzheimer's Disease trial and the companion Longitudinal Evaluation of Amyloid Risk and Neurodegeneration study (A4/LEARN,  = 388), the Harvard Aging Brain Study (HABS,  = 72), and Alzheimer's Disease Neuroimaging Initiative (ADNI,  = 412). Across all cohorts, we included participants with demographic data, including age, sex, education as measured in years, diagnosis, race/ethnicity classified as (self‐reported) Hispanic/Latino versus non‐Hispanic/Latino, ε4, as well as longitudinal cognitive performance and longitudinal magnetic resonance imaging (MRI). We conducted this study under the ethical guidelines stipulated by the Partners Human Research Committee, which is the Institutional Review Board for the Massachusetts General Hospital and Brigham and Women's Hospital. The study was carried out in accordance with the guidelines of the Declaration of Helsinki. Written informed consent was obtained from all participants. MRI: Three‐dimensional (3D) structural T1‐weighted MRI scans were acquired across all cohorts using previously detailed site‐specific scanners., , T1 images were segmented and parcellated using FreeSurfer software (version 6.0). Hippocampal volume (HV) and total gray matter volume were examined after adjusting for intracranial volume (ICV). MRI scans were selected based on closest date to each participant's tau positron emission tomography (PET) scan.