A China-based study, which tracked over 1,000 Covid-19 recovered patients aged 60 years and above for a year, has found that their cognitive abilities have declined and pushed them towards dementia.
Looking at changes in these patients after their hospital discharge, it has reported that 21 per cent of those with severe cases in this cohort experienced progressive cognitive decline, suggesting that Covid-19 can cause long-lasting damage than previously thought. The study notes that its findings imply “that the pandemic may substantially contribute to the world dementia burden in the future.”
The study followed up recovered patients, who were discharged between February and April 2020 from three Covid-19 designated hospitals in China, and concluded that “severe Covid-19 was associated with a higher risk of cognitive impairment at 12 months.” The severe cases more frequently experienced early-onset cognitive decline, late-onset cognitive decline and progressive cognitive decline, compared to non-severe cases and control individuals.
How was cognitive decline measured?
With pre-infection cognitive status not available for the participants, researchers mapped each patient for the first six months after discharge, using family informants as a base. They circulated the Chinese version of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), which contains 16 items that rate changes in memory and other cognitive domains in a scale of five, with 1 indicating “much improved” and five indicating “much worse.” For the study, cognitive decline was defined as a mean item score of 3.5 or higher.
Cognitive changes over the second six-month period post-discharge were assessed by changes in TICS-40 scores between six and 12 months. A decrease of three or more points was defined as clinically meaningful cognitive decline. Telephone interviews were conducted to assess cognition by using the Chinese version of the Telephone Interview of Cognitive Status-40 (TICS-40), which comprises 10 questions with a maximum score totalling to 40.
Questions included as part of TICS-40 included counting backwards, word list learning, subtractions, delay in word recall, last name of president or vice-president and so on. A score of 20 or lower was considered indicative of mild cognitive impairment (MCI), and a score of 12 or lower was considered indicative of dementia.
Participants with stable cognition in both the first and second halves of follow-up were categorised as having stable cognitive function. Participants with cognitive decline in the first half of follow-up but stable cognition in the second half were categorised as having early-onset cognitive decline. Participants without cognitive decline in the first half of follow-up but with cognitive decline in the second half of follow-up were categorised as having late-onset cognitive decline. Participants with cognitive decline in both the first and second halves of follow-up were categorised as having progressive cognitive decline.
Interpreting the findings
The study, published in the March edition of JAMA Neurology, notes that Covid-19 survivors had lower TICS-40 scores than control individuals at both six and 12 months after patient discharge. Individuals with severe cases had lower TICS-40 scores, indicating worse cognition, than those with non-severe cases and control individuals at six months and individuals with severe cases also had lower TICS-40 scores than those with non-severe cases and control individuals at 12 months. Individuals with non-severe cases and control individuals differed in IQCODE scores but not in TICS-40 scores during follow-up.
The overall incidence of cognitive impairment in survivors 12 months after discharge was 12.45 per cent. Among individuals with severe cases, 26 (10 per cent) had dementia and 69 (26 per cent) had mild cognitive impairment at six months, with the numbers increasing to 39 (15 per cent) for dementia and remaining at 68 (26.15 per cent) for mild cognitive impairment at 12 months. The numbers were higher than in those with non-severe cases and control individuals, indicating that severe COVID-19 was associated with a higher risk of cognitive impairment at 12 months.
Survivors of non-severe Covid-19 and control individuals had comparable frequencies of dementia and mild cognitive impairment at both six and 12 months. The IQCODE score (higher score indicates larger longitudinal cognitive decline) at six months of the follow-up was higher in individuals with severe cases than in those with non-severe cases, which in turn was higher than the score in control individuals. Specifically, 158 people with severe cases, 340 individuals with non-severe cases and 92 control participants reported cognitive decline within the first six months.
In the second six months, individuals with severe cases had a higher proportion of participants with cognitive decline than individuals with non-severe cases and control individuals. Moreover, individuals with severe cases had a higher speed of cognitive decline than those with non-severe cases and control individuals. However, no difference in speed of cognitive decline was found between individuals with non-severe cases and control individuals.
Compared to individuals with non-severe cases and control individuals, individuals with severe cases more frequently experienced early-onset cognitive decline, late-onset cognitive decline and progressive cognitive decline, while individuals with non-severe cases more frequently experienced early-onset cognitive decline than control non-infected individuals.
Why is the study significant and what have earlier studies found?
Post-infection cognitive outcomes following Covid-19 have been reported but the long-term dynamic trajectory of cognitive changes in Covid-19 survivors remains unclear.
While several studies have found that Covid-19 is associated with an increase in risk of being diagnosed with dementia within six months after infection, most studies so far have been small-scale (such as a Denmark study of 29 patients in March 2021) and have not had a year-long follow-up period (A US-based retrospective study from November 2020 of 62,354 Covid-19 patients that looked at psychiatric disorders reported up to three months after contracting the infection) that can help us understand the long-term COVID-19 impact on cognitive decline and the resultant dementia burden. Most studies, including one UK-based study published in The Lancet in April 2021, had a six month follow-up period.
Moreover, the China-based study, by comparing across various time-periods, establishes the progressive cognitive changes seen in those who reported severe and non-severe Covid-19 infection. The latest study notes that “Covid-19, especially severe Covid-19, may be associated with long-term cognitive impairment.”
Studies on the impact of Covid-19 on brains continue across the world. These include a small-scale Amsterdam-based study of targeted 20 recovered individuals, which commenced in February this year. The study is looking at neuroinflammation through PET scans, brain MRI and psychiatric evaluation to look at cognitive conditions and better understand the pathophysiological mechanisms of the virus.
Who were the study participants and who were not?
A total of 1,438 Covid-19 survivors (691 males and 747 females) with a median age of 69 years and 438 uninfected control individuals, with a median age of 67 years, completed the six and 12-month visits.
Recovered patients or control participants were not included if they had self-reported or diagnosed cognitive impairment prior to Covid-19 infection, if they had a family history of dementia in first-degree relatives, if they had a concomitant neurological disorder potentially affecting cognitive function, or if they had severe cardiac, hepatic, kidney diseases or any kind of tumour.