COVID-19 Pandemic-Related Exposures and Cognitive Function in Middle-Aged Women

Abstract

Importance: The COVID-19 pandemic has been associated with risk factors for cognitive decline, such as bereavement and SARS-CoV-2 infection.

Objective: To examine whether the COVID-19 pandemic and pandemic-related exposures are associated with cognitive function among middle-aged women.

Design, setting, and participants: This cohort study analyzed data from the Nurses' Health Study II, an ongoing study of registered nurses in the US. The present study focused on women aged 51 to 76 years who completed 2 to 8 objective cognitive assessments both prior to (October 1, 2014, to February 29, 2020) and during the COVID-19 pandemic (March 1, 2020, to September 30, 2022). Statistical analyses were performed from January 2023 to January 2025.

Exposure: COVID-19 pandemic.

Main outcomes and measures: Two standardized (ie, z-scored) composite cognitive scores (psychomotor speed and attention, learning and working memory) and a global score constituted the primary outcomes. Higher scores indicated better cognitive function. Cognitive function was assessed using the Cogstate Brief Battery, a computer-administered cognitive test battery. Participants completed cognitive assessments every 6 to 12 months.

Results: A total of 5191 women (mean [SD] age at first cognitive assessment, 63.0 [4.8] years) completed both prepandemic and during-pandemic measures, contributing 23 678 cognitive assessments. After adjustment for age at cognitive assessment, educational level for both participants and their parents, cognitive test practice effects, and comorbidities (eg, diabetes, hypertension), no difference in cognitive function was observed between assessments taken during vs before the pandemic (psychomotor speed and attention: β = -0.01 SD [95% CI, -0.05 to 0.02 SD]; learning and working memory: β = 0.00 SD [95% CI, -0.03 to 0.03 SD]; global score: β = 0.00 SD [95% CI, -0.03 to 0.02 SD]). Among 4456 participants who responded to the COVID-19 substudy (ie, surveys about pandemic-related events), those with a history of SARS-CoV-2 infection (164 [3.7%]) or post-COVID-19 conditions (PCC; 62 [1.4%]), at a median (IQR) 20.0 (18.5-22.1) months after initial infection, had reduced cognitive function compared with women without infection or PCC; however, these differences did not reach statistical significance, and the wide CIs suggested considerable uncertainty.

Conclusions and relevance: This cohort study of middle-aged women found that the COVID-19 pandemic and pandemic-related events were not associated with cognitive decline up to 2.5 years after the onset of the pandemic. Future studies are needed to examine the long-term implications of SARS-CoV-2 infection and PCC for cognitive function.

Figure 1.. Flowchart of Study Design

Figure 2.. Cogstate Cognitive Composite Scores During vs Before the COVID-19 Pandemic

The association of the pandemic with cognitive function was examined using linear mixed-effects models with normal distribution and identity link, unstructured covariance structure, and random intercept for each participant (number of assessments per person: 2-8 for prepandemic and during-pandemic assessments; 1-3 for wave 2 assessments). Pandemic as the independent variable was coded 1 if assessment was on or after or 0 if assessment was before March 1, 2020. The model was adjusted for various factors, including age at baseline; age-squared; time since first test; practice effects (number of tests taken × time since last test); wave; test platform; racial identity; parental educational level; participant educational level; time-varying body mass index; smoking status; and history of diabetes, hypertension, stroke, depression, and cancer. Wave 2 assessments were administered 2 years before and 2 years after the pandemic.