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.

Does covid-19 impair endogenous neurogenesis?

“…Impairments in neurogenesis, which have been demonstrated in several neurodegenerative disorders, could contribute to hyposmia and neurodegeneration (Figure 1). Consistent with this notion, chronic cognitive impairment has been shown to correlate with olfactory dysfunction due to COVID-19 [10]. Hyposmia during acute COVID-19 was linked with increased vulnerability in memory functions in several studies [82][83][84].…”

“…The same study reported an incidence of anosmia in 18% of participants. An association exists between severity of cognitive impairment and severity of olfactory symptoms in older people recovering from COVID-19 [10].…”

Olfactory loss is a predisposing factor for depression, while olfactory enrichment is an effective treatment for depression

“…But given the very large number of very different neurological disorders with very different etiologies, that possibility seems unlikely. Another possibility is that the olfactory loss precedes the neurological symptoms, which is the case for Alzheimer’s disease, Parkinson’s disease, the cognitive loss that can accompany long COVID, and depression ( Walker et al, 2021 ; Zamponi et al, 2021 ). Similarly, olfactory loss may precede all the disorders listed above and if olfactory loss precedes the cognitive, emotional, and motor symptoms, perhaps the olfactory loss plays a role in increasing the risk of developing these functional problems.…”

Demand Coupling Drives Neurodegeneration: A Model of Age-Related Cognitive Decline and Dementia

“…Increased risk of cognitive decline with loss of sense of smell—COVID as a recent example [ 135 , 136 ].…”