Post-COVID Cognitive and Functional Impairments Predicted by Anosmia, Not Infection Severity

Data presented at the 2022 Alzheimer’s Association International Conference, held July 31 to August 4, in San Diego, California, revealed that olfactory dysfunction, not COVID-19 infection severity, predicts persistent cognitive and functional impairments following SARS-CoV-2 infection.¹

A cohort of 766 Amerindian participants aged 60 years or older recruited from a provincial health registry were included in an analysis, 88.4% of whom were infected with COVID-19 and 11.6% who were not. None of the controls had olfactory dysfunction. Using a logistic regression model, lead investigator Gabriela Gonzalez-Aleman, LCP, PhD, Pontificia Universidad Catolica Argentina, and colleagues, found that severity of anosmia, not clinical status, significantly predicted cognitive impairment.

Patients included in the study underwent Schedules for Clinical Assessment in Neuropsychiatry (SCAN) and Clinical Dementia Rating scale (CDR) testing, along with neurocognitive assessments and emotional reactivity scale. Neurological assessments that included semiquantitative olfactory function test, motor function, coordination, and gait were also conducted. The mean age of the cohort was 66.9 years (±6.14), with mean education time of 10.36 years (±5.6).

Among both controls and infect patients, normalized z-scores showed that 11.7% of patients had memory only impairment (single-domain), 8.3% had impairments in attention and executive function without memory impairment (multiple domain), and 11.6% of individuals had multiple domain impairments relative to normal cognition. In the multidomain group, z-scores below –2, defined as cognitive impairment, were found in each task except for word list-long term memory (–1.59), 5-digit test-inhibition (–0.5) and 5-digit test-flexibility (–1.14).

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For the multiple domain group, only 2 tasks reached the criteria for cognitive impairment: oral trails-mental (–2.25) and oral trails-switching. None of the z-scores in the single domain group reached scores considered cognitive impairment. Functional memory impairment—defined as CDR scores of at least 1—were reported in two-third of infected patients, and the impairment was severe in half of them. Phone-based follow-up at 1 year revealed high adherence, as only 4 participants declined. Of the 1.5% of patients who did not receive at least 1 vaccine dose, 12.5% became reinfected. Rates of reinfection (range, 10% to 23%) were not affected by the vaccination schedule.

Smell alteration and cognitive impairment have been commonly reported as features of long-COVID syndrome. Recently, a multicenter, cross-sectional study found that smell alterations persisting over 6 months, cognitive impairment, and headache, were associated with more severe olfactory loss, consistent with neuroinflammatory mechanisms mediating a variety of long-COVID symptoms. Those who were affected by both mental clouding and headache showed increased risk of presenting with anosmia (odds ratio [OR], 41.0; P = .01), hyposmia and parosmia (OR, 13; P = .08), or hyposmia alone (OR, 9; P = .1), and moderate risk of parosmia (OR, 5; P = .3); however, statistically significant P values were identified for anosmia only.²

Additional research has suggested that olfactory impairment is associated with other markers that signal the emergence of prodromal AD. Auditory impairment has been associated with dementia in epidemiological studies and visual system deficits have been reported in AD; however, the emergence of these deficits in prodromal AD is unclear, with further research needed.

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REFERENCES
1. Gonzalez-Aleman G, et al. Olfactory dysfunction but not COVID-19 severity predicts severity of cognitive sequelae following SARS-CoV-2 infection in Amerindian older adults. Presented at: 2022 Alzheimer’s Association International Conference; July 31 to Aug 4; San Diego, CA; Abstract ID 66868.
2. Di Stadio A, Brenner MJ, De Luca P, et al. Olfactory dysfunction, headache, and mental clouding in adults with long-COVID-19: what is the link between cognition and olfaction? A cross-sectional study. Brain Sci. 2022;12(2):154. doi:10.3390/brainsci12020154.