Steeper memory decline after COVID-19 lockdown measures

Els D. Bakker, Stéphanie L. van der Pas, Marissa D. Zwan, Freek Gillissen, Femke H. Bouwman, Philip Scheltens, Wiesje M. van der Flier, Ingrid S. van Maurik

During COVID-19 lockdown measures, memory clinic patients reported worries for faster cognitive decline, due to loss of structure and feelings of loneliness and depression. We aimed to investigate the impact of the COVID-19 lockdown on rate of cognitive decline in a mixed memory clinic population, compared to matched historical controls. We included patients who visited Alzheimer Center Amsterdam 6 months to 1 week before the first Dutch COVID-19 lockdown, and had a second visit 1 year later, after this lockdown period (n = 113; 66 ± 7 years old; 30% female; n = 55 dementia, n = 31 mild cognitive impairment (MCI), n = 18 subjective cognitive decline (SCD), n = 9 postponed diagnosis). Historical controls (visit in 2016/2017 and second visit 1 year later (n = 640)) were matched 1:1 to lockdown patients by optimal Mahalanobis distance matching (both groups n = 113). Groups were well matched. Differences between lockdown patients and historical controls over time in Mini-Mental State Examination, Trail Making Test part A and B, Rey-Auditory Verbal Learning Test (RAVLT) immediate and delayed recall, and category fluency scores were analyzed using linear mixed effect models with random intercepts. We examined differences in rate of cognitive decline between whole groups, and after stratification in SCD, MCI, and dementia separately. Lockdown patients had a faster rate of memory decline compared to controls on both RAVLT immediate [B(SE) =  - 2.62 (1.07), p = 0.015] and delayed recall [B(SE) =  - 1.07 (0.34), p = 0.002]. Stratification by syndrome diagnosis showed that this effect was largely attributable to non-demented participants, as we observed faster memory decline during lockdown in SCD and MCI (RAVLT immediate [SCD: B(SE) =  - 6.85 (2.97), p = 0.027; MCI: B(SE) =  - 6.14 (1.78), p = 0.001] and delayed recall [SCD: B(SE) =  - 2.45 (1.11), p = 0.035; MCI: B(SE) =  - 1.50 (0.51), p = 0.005]), but not in dementia. Memory clinic patients, specifically in pre-dementia stages, showed faster memory decline during COVID-19 lockdown, providing evidence that lockdown regulations had a deleterious effect on brain health. In individuals that may have been able to deal with accumulating, subclinical neuropathology under normal and structured circumstances, the additional stress of lockdown regulations may have acted as a "second hit," resulting in less beneficial disease trajectory.