Studies demonstrate 'clear connections' between COVID-19, cognitive issues
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Forgetfulness continued in more than half of older adults studied between 3 to 6 months after COVID-19, while one in four experienced added issues with cognition, including language and executive dysfunction.
These problems correlated with persistent issues related to smell function, but not with the severity of the original COVID-19 infection, according to the findings presented during the Alzheimer’s Association International Conference.
A second study on COVID-19 presented during the meeting showed that biological markers of brain injury, neuroinflammation and Alzheimer’s disease were “strongly” associated with neurological symptoms in patients with COVID-19. Further, a third study demonstrated that individuals with cognitive decline following COVID-19 infection were more likely to experience low blood oxygen levels after limited physical exertion and poor overall physical condition.
“We’re starting to see clear connections between COVID-19 and problems with cognition months after infection,” Gabriel de Erausquin, MD, PhD, MSc, a specialist in neurology and psychiatry at The University of Texas Health Science Center at San Antonio Long School of Medicine, said in a press release. “It’s imperative we continue to study this population, and others around the world, for a longer period of time to further understand the long-term neurological impacts of COVID-19.”
Cognitive impairment persists after COVID-19
In the first study, de Erausquin and colleagues examined cognition and olfactory senses in adults aged 60 years and older from Argentina who had COVID-19 infection. The researchers performed interviews using the Schedules for Clinical Assessment in Neuropsychiatry (SCAN) and Clinical Dementia Rating scale; a neurocognitive assessment; an assessment on an emotional reactivity scale; and a neurological assessment that involved a semiquantitative olfactory function test and tests of motor function, coordination and gait.
The researchers examined 233 patients with COVID-19 and 64 control participants; mean age of the study population was 66.7 years. The reported average duration for formal learning among the study cohort was 9.35 years. Normative data for the local population were available for Word list, Corsi Blocks, Oral Trails and Five Digit Tests, according to the study results. De Erausquin and colleagues used this information to normalize z scores and classify the sample into three groups: normal cognition (44.6%), memory-only impairment (21%) and multiple domain impairment (34.4%).
Individuals with multiple domain impairment experienced “severe alterations” in short-term memory, semantic memory, naming, executive function and attention compared with those who had normal cognition or memory-only impairment. The researchers found that severity of cognitive impairment was significantly associated with severity of olfactory dysfunction (P = .003), but not severity of acute COVID-19 infection.
“Older adults frequently suffer persistent cognitive impairment after recovery from [COVID-19] infection,” the researchers wrote. “Cognitive impairment is correlated with persistent anosmia.”
COVID-19 may accelerate AD-related symptoms, pathology
In another study presented during the Alzheimer’s Association International Conference, researchers found that serum biomarkers of neuronal injury, neuroinflammation and Alzheimer’s disease such as neurofilament light (NfL), total tau (t-tau), ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1), glial fibrillary acid protein (GFAP) and phosphorylated tau (pTau-181) correlate strongly with the presence of neurological symptoms among patients with COVID-19. These results showed that patients who had COVID-19 may have an acceleration of AD/AD-related dementias symptoms and pathology, according to the study results from Thomas M. Wisniewski, MD, Gerald J. and Dorothy R. Friedman Professor at New York University Alzheimer’s Disease Center and professor of neurology, pathology and psychiatry at New York University Grossman School of Medicine, and colleagues.
The researchers examined patients admitted to three sites within the New York University Langone Health system. They analyzed plasma from 310 patients, including 158 with a positive COVID-19 test and neurological symptoms and 152 with a positive COVID-19 test without neurologic symptoms, performing plasma biomarker assays for t-tau, NfL, GFAP, UCH-L1, amyloid beta 40, amyloid beta 42 and pTau-181.
Plasma biomarker assays for t-tau, NfL, GFAP and UCH-L1 demonstrated “a significant elevation” in patients with COVID-19 who had neurological symptoms compared with those with COVID-19 and no neurological symptoms: NfL (two-tailed t-test, P = .0003), GFAP (two-tailed t-test, P = .0098), UCH-L1 (two-tailed t-test, P = .0138) and t-tau (two-tailed t-test, P = .04). Study results demonstrated that pTau-181 was also increased among patients with COVID-19 who had neurological symptoms (two-tailed t-test, P = .0141).
Wisniewski and colleagues observed no significant differences with amyloid beta 1-40. However, both amyloid beta 1-42 and the pTau/amyloid beta 42 ratio demonstrated significant differences among patients with neurological symptoms (two-tailed t-test, P = .049 and P = .0017, respectively).
“These findings suggest that patients who had COVID-19 may have an acceleration of Alzheimer’s-related symptoms and pathology,” Wisniewski said. “However, more longitudinal research is needed to study how these biomarkers impact cognition in individuals who had COVID-19 in the long term.”
Oxygen deprivation may contribute to cognitive issues
A third study on COVID-19 presented at the Alzheimer’s Association International Conference examined cognitive impairment and related health measures among 32 patients who had been hospitalized with mild to moderate COVID-19. The researchers examined these patients two months after discharge.
George Vavougios, MD, PhD, a postdoctoral researcher at the University of Thessaly in Greece, and colleagues found that 56.2% of these patients presented with cognitive decline. They also observed that short-term memory impairment and multi-domain impairment with no short-term memory deficits represented “the predominant patters of cognitive impairment,” according to the press release. Scores on the Montreal Cognitive Assessment correlated with age (P = .003), waist circumference (P = .028) waist-to-hip ratio (P = .042) and oxygen saturation during the 6-minute walk test (1st, 4th and 6th minute; P < .05). Multiple linear regression models demonstrated that, after adjustments for age and sex, oxygen saturation at the 6th minute of the 6-minute walk test correlated independently with scores on the Montreal Cognitive Assessment (beta = 0.579; P = .001).
“A brain deprived of oxygen is not healthy, and persistent deprivation may very well contribute to cognitive difficulties,” Vavougios said in the press release. “These data suggest some common biological mechanisms between COVID-19’s dyscognitive spectrum and post-COVID-19 fatigue that have been anecdotally reported over the last several months.”
Reference:
Alzheimer’s Association. COVID-19 associated with long-term cognitive dysfunction, accelerations of Alzheimer’s symptoms. Available at: https://www.alz.org/aaic/releases_2021/covid-19-cognitive-impact.asp. Accessed July 29, 2021.
Perspective
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Heather M. Snyder, PhD
While we work to understand the lasting impact that COVID-19 may have on our brains, there is a message for all of us: Do not get COVID-19. Get vaccinated. Follow guidelines from the CDC or your local health department.
It’s important to note that, even if you get COVID-19, you are not definitively going to experience brain changes. Some individuals who have had COVID-19 do experience brain changes. New research that is being presented at the Alzheimer’s Association International Conference suggests that some individuals may continue to have memory changes for a longer period. Other studies are suggesting that there are changes in the brain that are associated with underlying AD pathology. What this means for long-term risk, whether this is reversible or will continue, is an unanswered question.
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