Temporal Association Between COVID-19 Infection and Subsequent New-Onset Dementia in Older Adults: A Systematic Review and Meta-Analysis

Background: The relationship between COVID-19 infection and the increased likelihood of older adults developing new-onset dementia (NOD) remains elusive. This review primarily aimed to investigate the potential role of COVID-19 in leading to NOD among older adults aged 60 years and older over various time intervals.Methods: A thorough search was performed across several databases including MEDLINE/PubMed, PsycINFO, Scopus, medRxiv, and PQDT Global for studies published in English from January 2020 to December 2023. We assessed the risk of developing NOD, using Risk Ratio (RR) for measurement. The control groups were categorized as: (i) a non-COVID cohort with other respiratory infections [control group (C1)]; and (ii) a non-COVID cohort with otherwise unspecified health statuses [control group (C2)]. Follow-up periods were divided into intervals of 3, 6, 12, and 24 months post-COVID. The study protocol was registered with PROSPERO (CRD42023491714).Results: Our review incorporated 11 studies, encompassing 939,824 post-COVID-19 cases and 6,765,117 controls. The overall pooled analysis revealed a significant link between COVID-19 infection and an increased risk of NOD (RR = 1.58, 95% CI 1.21–2.08). In subgroup analyses, NOD risk was significantly higher in the COVID-19 group compared to C2 at 12 months post-COVID (RR = 1.84, 95% CI 1.41–2.38), but not at 3 (RR = 0.87, 95% CI 0.46–1.65) or 6 months (RR = 1.73, 95% CI 0.72–4.14). Compared to C1, the risk increase was not significantly remarkable at 3 (RR = 0.94, 95% CI 0.35–2.57), 6 (RR = 1.13, 95% CI 1.07–1.20), and 12 months (RR = 1.12, 95% CI 0.91–1.38), and overall (RR = 1.13, 95% CI 0.92–1.38). Female had a significantly higher risk of developing NOD in the COVID-positive group (RR = 1.65, 95% CI 1.53–1.78) and C2 group (RR = 1.33, 95% CI 1.22–1.44). Patients with severe COVID-19, as classified by the American Thoracic Society guidelines, were significantly much more prone to developing NOD than those with non-severe infections (RR = 17.58, 95% CI 10.48–29.49). Cognitive impairment was nearly twice as likely in COVID-19 survivors compared to those uninfected (RR = 1.93, 95% CI 1.52–2.43).Discussion: COVID-19 infection may be linked to a higher risk of NOD in recovered old adults at the subacute and chronic stages following COVID-19 diagnosis. This risk appears to be on par with that associated with other respiratory infections.Funding: None.Declaration of Interest: All authors declare no financial or non-financial conflicts of interest.