Title : The impact of covid-19-associated Anosmia on cognitive trajectory in an aging population
Abstract:
Introduction: The COVID-19 pandemic brought renewed attention to the relationship between sensory function and brain health, most notably with the emergence of long-term anosmia among a significant portion of patients. Beyond its impact on quality of life, olfactory dysfunction has been increasingly linked to cognitive impairment and neurodegenerative risk, especially among older adults. This study investigates the relationship between post-COVID anosmia and cognitive trajectory, aiming to improve post-COVID management strategies in an aging population.
Methods: A retrospective cohort analysis was conducted using the TriNetX Research Network, a federated,
multi-institutional database comprising deidentified electronic medical records (EMRs) from 109 healthcare organizations. Adult patients (≥18 years) with a documented diagnosis of COVID-19 between January 1, 2016 and January 1, 2023 were identified. Patients were stratified into two cohorts: those with anosmia and without anosmia. Individuals with a prior diagnosis of the outcomes of interest were excluded.
The primary outcomes included incident dementia, Alzheimer’s disease, Parkinson’s disease, and mild cognitive degeneration. Outcomes were assessed at 1-, 3-, and 5-year intervals following the index event.
Propensity score matching (1:1) resulted in two matched groups of 29,268 patients each. Risk ratios (RR), risk differences (RD), odds ratios (OR), 95% confidence intervals (CI), and p-values were calculated. Kaplan–Meier survival analyses with log-rank tests and hazard ratios were also performed. Statistical significance was defined as p < 0.05.
Results: At 1-year and 5-year follow-up, no significant associations were observed between post-COVID anosmia and risk of dementia, Alzheimer’s disease, Parkinson’s disease (all p > 0.05), though there was significant association with mild cognitive degeneration at 1 year [RR = 2.601, 95% CI (1.798, 3.762); RD = 0.002, p < 0.001] and 5 years [RR = 1.694, 95% CI (1.397, 2.055); RD = 0.004, p < 0.001. At 3 years, however, post-COVID anosmia was significantly associated with increased risk of Parkinson’s disease [RR = 1.820, 95% CI (1.260, 2.629); RD = 0.001, p = 0.001] and mild cognitive impairment [RR = 1.768, 95% CI (1.436, 2.178); RD = 0.004, p < 0.001]. No significant associations were observed for dementia [RR = 1.138, 95% CI (0.908, 1.427); RD = 0.001, p = 0.262] or Alzheimer’s disease [RR = 1.179, 95% CI (0.839, 1.658); RD = 0.000, p = 0.343] at 3 years.
Discussions: Post-COVID anosmia was not linked to elevated risk of dementia or Alzheimer’s disease across 1-, 3-,
or 5-year follow-up. However, significant associations emerged at 3 years, with anosmia predicting higher incidence of Parkinson’s disease and mild cognitive impairment. The absence of findings at 5 years could reflect a dilution of effect because of attrition and competing risks, or that anosmia confers a temporally specific vulnerability window for neurodegenerative emergence. Clinically, these findings underscore the importance of long-term neurological surveillance among patients with post-COVID anosmia, particularly for signs of parkinsonism or early cognitive impairment. Early identification of at-risk individuals may open opportunities for timely interventions, lifestyle modifications, and enrollment in neuroprotective trials.
