Olfactory dysfunction and chronic cognitive impairment following SARS-CoV-2 infection in a sample of older adults from the Andes mountains of Argentina

Abstract: Background: COVID-19 has affected more than 150 million people. The causal coronavirus, SARS-CoV-2 has infected twice as many individuals who have remained asymptomatic. COVID-19 includes central nervous system (CNS) manifestations and may result in chronic neuropsychiatric sequelae. Risk factors for COVID-19 sequelae overlap with those for Alzheimer’s disease (AD), particularly older age and ApoE4 status. The Alzheimer’s Association Consortium on Chronic Neuropsychiatric Sequelae of SARS-CoV-2 infection (CNS SC2) established harmonized definitions, ascertainment and assessment methodologies to evaluate and longitudinally follow up cohorts of older adults with variable exposure to COVID-19. We present preliminary data from CNS SC2 in a prospective cohort of 234 older adult Amerindians from Argentina. Method: Participants are ≥ 60 years recruited from the health registry of the Province of Jujuy containing all SARS-CoV-2 testing data (regardless of clinical status and of the result of the testing). We randomly invite older adults stratified by testing status regardless of symptom severity, a minimum of 3 months after clinical recovery (maximum 6 months); refusal to participate is <45%. Assessment includes interview with the Schedules for Clinical Assessment in Neuropsychiatry (SCAN) and Clinical Dementia Rating scale; neurocognitive assessment; emotional reactivity scale; and neurological assessment including semiquantitative olfactory function test, motor function, coordination and gait. We present here the results of olfactory testing and cognitive assessments. Result: We assessed 233 infected participants and 64 controls. Average duration of formal learning is 9.35 ± 2.6 years and mean age is 66.7 ± 5.13 years. Normative data for the local population were available for Word list, Corsi Blocks, Oral Trails and Five Digit Tests and were used to normalize Z-scores and categorize the sample in 3 groups: normal cognition (NC,44.6%); memory only impairment (MOI,21%); and multiple domain impairment (MDI,34.4%). Individuals with MDI presented severe alterations in short-term memory; semantic memory; naming; executive function and attention compared to NC or MO groups (Table 1). Severity of cognitive impairment was significantly correlated with severity of olfactory dysfunction (χ2 = 13.82; p= 0.003) but not severity of acute COVID-19. Conclusion: Older adults frequently suffer persistent cognitive impairment after recovery from SARS-CoV-2 infection; cognitive impairment is correlated with persistent anosmia

Olfactory dysfunction but not COVID-19 severity predicts severity of cognitive sequelae following SARS-CoV-2 infection in Amerindian older adults

Abstract Background: COVID-19 has affected more than 380 million people. Infections may result in long term sequelae, including neuropsychiatric symptoms. In older adults COVID-19 sequelae resemble early Alzheimer’s disease, and may share risk factors and blood biomarkers with it. The Alzheimer’s Association Consortium on Chronic Neuropsychiatric Sequelae of SARS-CoV-2 infection (CNS SC2) established harmonized definitions, ascertainment and assessment methodologies to evaluate and longitudinally follow up cohorts of older adults with exposure to COVID-19. We present one year data in a prospective cohort from Argentina. Method: Participants (n = 766) are older adults (≥60 years) recruited from the provincial health registry containing all SARS-CoV-2 testing data. We randomly invite older adults stratified by PCR COVID-19 testing status regardless of symptom severity, between 3 and 6 months after recovery. Assessment includes interview with the Schedules for Clinical Assessment in Neuropsychiatry (SCAN) and Clinical Dementia Rating scale (CDR); neurocognitive assessment; emotional reactivity scale; and neurological assessment including semiquantitative olfactory function test, motor function, coordination and gait. Result: We assessed 88.4% infected participants and 11.6 % controls. Education is 10.36 ± 5.6 years and age is 66.9 ± 6.14 years. Level of care during COVID-19 is described in Figure 1. Normalized cognitive Z-scores categorize the cohort in 3 groups with decreased performance compared to normal cognition: memory only impairment (Single-domain,11.7%); impairment in attention+executive function without memory impairment (Two-domain, 8.3%); and multiple domain impairment (Multiple domain,11.6%). Logistic regression showed that severity of anosmia, but not clinical status, significantly predicts cognitive impairment. No controls had olfactory dysfunction. Cognitive impairment is defined as Z-scores below (- 2) (Table 1). Clinical assessment with SCAN revealed functional memory impairment in two thirds of infected patients (CDR ≥ 1), which was severe in half of them. Phone-based follow up at 1 year revealed high adherence (4 participants declined). Five were deceased at follow up. Rates of re-infection (between 10 and 23%) were not affected by the vaccination schedule (Table 2). Conclusion: The longitudinal cohort had very high adherence. Persistent cognitive and functional impairment after SARS-CoV-2 infection is predicted by persistent anosmia but not by the severity of the initial COVID-19 disease