Subjective cognitive decline and anxious/depressive symptoms during the COVID-19 pandemic: what is the role of stress perception, stress resilience, and β-amyloid?
Authors: Akinci Muge , Sánchez-Benavides Gonzalo , Brugulat-Serrat Anna , Peña-Gómez Cleofé , Palpatzis Eleni , Shekari Mahnaz , Deulofeu Carme , Fuentes-Julian Sherezade , Salvadó Gemma , González-de-Echávarri José Maria , Suárez-Calvet Marc , Minguillón Carolina , Fauria Karine , Molinuevo José Luis , Gispert Juan Domingo , Grau-Rivera Oriol , Arenaza-Urquijo Eider M. ,   for the ALFA Study, Beteta Annabella , Cacciaglia Raffaele , Cañas Alba , Cumplido Irene , Dominguez Ruth , Emilio Maria , Falcon Carles , Hernandez Laura , Huesa Gema , Huguet Jordi , Marne Paula , Menchón Tania , Operto Grégory , Polo Albina , Rodríguez-Fernández Blanca , Pradas Sandra , Sadeghi Iman , Soteras Anna , Stankeviciute Laura , Vilanova Marc , Vilor-Tejedor Natalia 
Published: September 2022

Abstract
Background
The COVID-19 pandemic may worsen the mental health of people reporting subjective cognitive decline (SCD) and therefore their clinical prognosis. We aimed to investigate the association between the intensity of SCD and anxious/depressive symptoms during confinement and the underlying mechanisms.

Methods
Two hundred fifty cognitively unimpaired participants completed the Hospital Anxiety and Depression Scale (HADS) and SCD-Questionnaire (SCD-Q) and underwent amyloid-β positron emission tomography imaging with [18F] flutemetamol (N = 205) on average 2.4 (± 0.8) years before the COVID-19 confinement. During the confinement, participants completed the HADS, Perceived Stress Scale (PSS), Brief Resilience Scale (BRS), and an ad hoc questionnaire on worries (access to primary products, self-protection materials, economic situation) and lifestyle changes (sleep duration, sleep quality, eating habits). We investigated stress-related measurements, worries, and lifestyle changes in relation to SCD. We then conducted an analysis of covariance to investigate the association of SCD-Q with HADS scores during the confinement while controlling for pre-confinement anxiety/depression scores and demographics. Furthermore, we introduced amyloid-β positivity, PSS, and BRS in the models and performed mediation analyses to explore the mechanisms explaining the association between SCD and anxiety/depression.

Results
In the whole sample, the average SCD-Q score was 4.1 (± 4.4); 70 (28%) participants were classified as SCD, and 26 (12.7%) were amyloid-β-positive. During the confinement, participants reporting SCD showed higher PSS (p = 0.035) but not BRS scores (p = 0.65) than those that did not report SCD. No differences in worries or lifestyle changes were observed. Higher SCD-Q scores showed an association with greater anxiety/depression scores irrespective of pre-confinement anxiety/depression levels (p = 0.002). This association was not significant after introducing amyloid-β positivity and stress-related variables in the model (p = 0.069). Amyloid-β positivity and PSS were associated with greater HADS irrespective of pre-confinement anxiety/depression scores (p = 0.023; p < 0.001). The association of SCD-Q with HADS was mediated by PSS (p = 0.01).

Conclusions
Higher intensity of SCD, amyloid-β positivity, and stress perception showed independent associations with anxious/depressive symptoms during the COVID-19 confinement irrespective of pre-confinement anxiety/depression levels. The association of SCD intensity with anxiety/depression was mediated by stress perception, suggesting stress regulation as a potential intervention to reduce affective symptomatology in the SCD population in the face of stressors.