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Brain health deteriorated more rapidly for people 50 and older during the COVID-19 pandemic, data from the PROTECT study in England suggested.

Across the entire cohort of 3,100 people, both executive function (effect size 0.15) and working memory (effect size 0.51) worsened during the first year of the pandemic, according to Anne Corbett, PhD, of the University of Exeter in England, and colleagues.

These trends were echoed in people with mild cognitive impairment (effect sizes 0.13 and 0.40, respectively) and in people who had COVID-19 (effect sizes 0.24 and 0.46), the researchers reported in .

In the second year of the pandemic, worsening working memory was sustained across the entire cohort (effect size 0.47). Changes were associated with known dementia risk factors, including increased alcohol use and reduced exercise.

"Our findings suggest that lockdowns and other restrictions we experienced during the pandemic have had a real lasting impact on brain health in people aged 50 or over, even after the lockdowns ended," Corbett said in a statement.

"This raises the important question of whether people are at a potentially higher risk of cognitive decline which can lead to dementia," she noted.

"Our findings also highlight the need for policymakers to consider the wider health impacts of restrictions like lockdowns when planning for a future pandemic response," Corbett added.

Despite much progress in understanding the virology, transmission, and pathogenesis of SARS-CoV-2, the long-term consequences of COVID-19 and pandemic restrictions are largely unknown, observed Dorina Cadar, PhD, of Brighton and Sussex Medical School in Brighton, England, in an .

"Although initially thought to cause acute respiratory symptoms, the effects of SARS-CoV-2 on other systems -- including the central and peripheral nervous system -- is becoming increasingly clear," Cadar wrote.

Evidence for pandemic-associated effects of isolation, loneliness, post-traumatic stress, depression, fear, anger, and confusion is "overwhelming," she added.

Corbett and colleagues assessed neuropsychology test data from 3,142 participants ages 50 and older in the U.K. study. About half of the cohort (54%) were women, mean age was 67.5, and 98% were white. A total of 752 participants had SARS-CoV-2 infection during the course of the study and 147 had mild cognitive impairment.

Data were collected from the same people at three time points: before the pandemic (March 2019 through February 2020), and during its first (March 2020 through February 2021) and second (March 2021 through February 2022) years. Evaluations included logical reasoning and problem-solving tests to assess executive function and three working memory tests. Participants also reported lifestyle factors and underwent depression assessments annually.

Cognitive decline was significantly associated with reduced exercise (P=0.0049 for executive function) and increased alcohol use (P=0.049 for working memory) across the whole cohort. Declines in working memory were linked with depression (P=0.011) in those with a history of COVID-19, and with loneliness (P=0.0038) in those with mild cognitive impairment.

In the second year of the pandemic, reduced exercise continued to be linked with lower executive function across the whole cohort. Relationships were sustained between worsening working memory and reduced exercise, loneliness, and depression in those who had COVID, and increased alcohol use, loneliness, and depression in those with mild cognitive impairment.

"The sustained decline in cognition highlights the need for public health interventions to mitigate the risk of dementia -- particularly in people with mild cognitive impairment, in whom conversion to dementia within 5 years is a substantial risk," Corbett and colleagues noted. "Long-term intervention for people with a history of COVID-19 should be considered to support cognitive health."

The study has limitations, the researchers acknowledged. The PROTECT cohort is self-selected and is biased toward people with higher education levels, they noted. Subgroup analyses were exploratory and the number of people in the mild cognitive impairment group was relatively small. Importantly, causality cannot be assumed, they cautioned, and other confounding factors may have influenced results.

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