To Örebro University

BACKGROUND: In 2022, the rapid spread of the highly transmissible Omicron variant precipitated a dramatic surge in infections and a subsequent societal shutdown in Shanghai. It offers the opportunity to examine the impact of COVID-19 pandemic on cognitive decline among community-dwelling older adults.

METHODS: The Shanghai Aging Study enrolled 3792 community residents aged ≥ 50 from 2010 to 2012 in central Shanghai. Demographics, medical history, ApoE genotyping, and plasma phosphorylated tau 217 (p-tau217), phosphorylated tau 181 (p-tau181), and neurofilament light chain (NfL) were collected at baseline. Cognitive function assessment and MRI scans were conducted at baseline and follow-up visits from 2014 to 2024. Study periods were defined as Wave 1 (Jan.2010-Dec.2012, baseline, pre-pandemic), Wave 2 (Jan.2014-Mar.2022, pre-pandemic), and Wave 3 (Jun.2022-Dec.2024, post-pandemic). Event study, difference-in-differences (DID), and linear mixed-effects models were employed to evaluate the pandemic's impact on cognitive trajectories and brain structural changes.

FINDINGS: We observed steeper age-related declines of the Mini-Mental State Examination (MMSE) during Wave 3. The event study model adjusting for age, sex, and education, showed significant MMSE decline in Wave 3, but not in Wave 2. Declines were more pronounced in individuals with high baseline plasma p-tau217, p-tau181, and NfL, ApoE-ε4 carriers, those with multi-comorbidities, or long-term medication use. The DID and linear mixed-effects models with individual-specific follow-up data revealed accelerated declines in global cognition, executive and language function, and structural brain atrophy from Wave 2-3, compared with Wave 1-2.

INTERPRETATION: The COVID-19 pandemic significantly accelerated cognitive and brain structural changes in community-dwelling older adults, particularly among those with pre-existing AD pathology or health vulnerabilities. These findings provide evidence of COVID-19 pandemic-related cognitive decline and highlight the need for mechanistic research into how direct and indirect stressors converge to drive cognitive impairment.