Cognitive impairment was more common among COVID-19 patients 60 years and older—particularly those with severe illness—released from hospitals in Wuhan, China, than among their uninfected peers, according to a 1-year follow-up study yesterday in JAMA Neurology.
A team led by researchers at Daping Hospital in Chongqing, China, followed 1,438 COVID-19 survivors aged 60 and older released from one of three dedicated COVID-19 hospitals in Wuhan from Feb 10 to Apr 10, 2020, and compared them with 438 of their uninfected spouses.
Because pre-COVID cognitive status wasn't available, family members provided their perceptions of cognitive changes using the Chinese version of the short form of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). The questionnaire contains 16 items that rate changes in memory and other domains, with decline defined as an item score of 3.5 or higher.
Trained raters interviewed COVID-19 patients at 12 months over the phone to evaluate cognition using the Chinese version of Telephone Interview of Cognitive Status-40 (TICS-40), which includes 10 variables and has a maximum of 40 points. A score of 20 or lower was considered indicative of mild cognitive impairment (MCI), while a score of 12 or lower indicated dementia, and a decrease of 3 points or more was considered clinically meaningful cognitive decline.
Of the COVID-19 patients. 48.1% were men, median age was 69 years, and none had a history of dementia. The control group was 50.7% men, and the median age was 67 years.
Severe COVID tied to higher risk
The incidence of impaired cognition among COVID-19 survivors was 12.5% 12 months after hospital release. COVID-19 survivors had lower TICS-40 scores than controls at both 6 months (median, 29 vs 30 points) and 12 months (29 vs 31).
Severely ill patients had lower TICS-40 scores than those with milder illness and controls (median score, 24 vs 30 vs 31) at 6 months; at 12 months, they had lower scores than controls (22.5 vs 31). Patients with mild or moderate illness and controls differed in IQCODE scores but not TICS-40 over follow-up.
Among severely ill COVID-19 patients, 10.0% had dementia and 26.5% had MCI at 6 months. At 12 months, 15.0% had dementia and 26.2% had MCI, much higher than in those with milder illness (dementia, 0.8%; MCI, 5.4%) and controls (dementia, 0.7%; MCI, 5.0%). Survivors of mild or moderate COVID-19 and controls had similar incidences of dementia and MCI at both 6 and 12 months.
Severe illness was tied to a higher risk of early-onset cognitive decline (odds ratio [OR], 4.9; 95% confidence interval [CI], 3.3 to 7.2), late-onset cognitive decline (OR, 7.6; 95% CI, 3.6 to 16.0), and progressive cognitive decline (OR, 19.0; 95% CI, 9.1 to 39.5), while milder COVID-19 was associated with a higher risk of early-onset cognitive decline (OR, 1.7; 95% CI, 1.3 to 2.3) after adjusting for age, sex, educational attainment, body mass index (BMI), and underlying illnesses.
The prevalence of progressive decline was 21.2% with severe COVID-19, 1.2% with non-severe COVID-19, and 2.3% in controls.
Severe COVID-19 was linked to a higher risk of cognitive impairment at 12 months (OR, 9.1; 95% CI, 5.6 to 14.8), but milder illness was not (OR, 1.1; 95% CI, 0.7 to 1.8), after adjusting for age, sex, educational attainment, BMI, and underlying illnesses.
Among a subset of 438 patients and their spouses, COVID-19 survivors were older (median age, 68 vs 67 years) and had a higher incidence of hypertension (47.0% vs 34.5%). Both nonsevere (OR, 1.8; 95% CI, 1.1 to 3.0) and severe COVID-19 (OR, 5.9; 95% CI, 3.6 to 9.8) in this group were tied to a higher risk of cognitive impairment at 12 months, after adjustment for risk factors.
Potential contributor to dementia burden
The study authors noted that impaired cognition is common in the months after COVID-19 infection, especially among older patients. "It is worth noting that 21% of individuals with severe cases in this cohort experienced progressive cognitive decline, suggesting that COVID-19 may cause long-lasting damage to cognition," they wrote.
"These findings imply that the pandemic may substantially contribute to the world dementia burden in the future."
Potential factors in post-COVID cognitive decline, the authors said, include long-term low oxygen levels, chronic systemic inflammation, and direct viral invasion of the brain and resultant neuronal damage.
"In this cohort study of COVID-19 survivors 60 years and older who were discharged from COVID-19–designated hospitals in Wuhan, China, SARS-CoV-2 infection, especially severe infection, was associated with an increase in risk of longitudinal cognitive decline," the researchers concluded. "The findings highlight the importance of immediate measures to deal with this challenge."
