Sex, caregiver status and amyloid positivity predict increased anxiety and depression during the COVID‐19‒related confinement
Authors: Akinci Muge , Operto Greg , Fuentes‐Julian Sherezade , Sánchez‐Benavides Gonzalo , Peña‐Gomez Cleofé , Milà‐Alomà Marta , Salvadó Gemma , Sala‐Vila Aleix , Grau‐Rivera Oriol , Suarez‐Calvet Marc , Cacciaglia Raffaele , Gramunt Nina , Molinuevo Jose , Navarro Arcadi , Minguillón Carolina , Fauria Karine , Gispert Juan Domingo , Arenaza‐Urquijo Eider M 
Published: December 2021

AbstractBackgroundAnxiety and depression are more prevalent in women and caregivers and are associated with increased Alzheimer’s disease (AD) risk. We investigated multimodal predictors of increased anxiety/depression during the Covid19‐related confinement in cognitively unimpaired (CU) older adults with an increased risk for AD with a special focus on sex/gender.MethodWe included 921 CU participants from the ALFA study (Table 1). Anxiety and depression (Hospital Depression and Anxiety Scale, HADS), perceived stress (Perceived Stress Scale, PSS) and stress resilience (Brief Resilience Scale, BRS) were measured during Covid19‐related confinement. A subgroup completed the HADS (n=767) and underwent [18F]flutemetamol‐PET imaging and sMRI (n=254) 2.4±0.8 years before confinement. Cross‐sectional anxiety/depression measurements and change in anxiety/depression (delta score) from baseline to confinement were our primary outcomes of interest. We considered amyloid status (+/‐) and cortical thickness (Cth) from the AD signature regions as imaging biomarkers. First, we investigated sex differences in the variables assessed during confinement. Second, we ran regression models to predict (i) cross‐sectional anxiety/depression scores during confinement and (ii) change in anxiety/depression from baseline to confinement. Age, sex, education, APOE‐ε4 status, caregiver status, stress related‐variables and imaging biomarkers were considered as predictors.ResultFifteen percent of the participants were caregivers, 69% of which were women. Women showed increased stress perception relative to men (p=<0.001) – notably, when they were caregivers (p=0.01). There were no sex‐differences in stress resilience (p=0.5). In cross‐sectional models, sex (women) and higher stress perception were independent predictors of greater anxiety/depression during confinement (Table 2a). Being a caregiver additionally predicted increase in anxiety/depressive symptomatology from baseline (Table 3a). Finally, in the subsample with biomarkers, amyloid positivity ‐ but not Cth in the AD signature ‐ contributed to predict anxiety/depression both cross‐sectionally (Table 2b) and longitudinally (Table 3b) along with sex (women), caregiver status and stress perception.ConclusionOur results showed sex differences in caregiver status and stress perception during the Covid19‐related confinement. Further, women, caregivers and those with higher self‐perceived stress showed an increase in anxiety/depressive symptomatology. Amyloid pathology prior to confinement was associated with greater levels of anxiety/depression suggesting a role of amyloid pathology in anxiety/depressive symptomatology.