Not peer reviewed.
The risk of cognitive decline and dementia in older adults diagnosed with COVID-19: A systematic review and meta-analysis.
Highlights
- COVID-19 linked to 65% of new-onset cognitive impairment
- Time since infection may impact cognitive outcomes
- Cognitive impairment is an important sequela of COVID-19
Abstract
Background
Cognitive impairment can be caused by infections with various pathogens, including SARS-CoV-2. Research has yet to determine the true incidence and course of cognitive impairment in older adults following COVID-19. Furthermore, research has theorised that COVID-19 is associated with dementia progression and diagnosis but this association has yet to be fully described.
Methods
A systematic review was registered in Prospero and conducted on the databases PubMed, Embase, Ovid, CENTRAL and Cochrane Library. Studies reporting cognitive impairment and dementia outcomes in post-acute and post-COVID-19 patients aged ≥65 years, and which included control data, were included in this review.
Results
15,124 articles were identified by the search strategy. After eliminating duplicate titles and completing title, abstracts and full-text review, 18 studies were included comprising of 412,957 patients with COVID-19 (46.63% male) and 411,929 patients without COVID-19 (46.59% male). The overall mean Montreal Cognitive Assessment (MoCA) score in COVID-19 patients was 23.34 out of 30 (95% CI [22.24, 24.43]). indicating cognitive impairment. The overall proportion of patients identified as having new onset cognitive impairment was 65% (95% CI [44, 81]). Subgroup analyses indicated that time since infection significantly improves overall MoCA score and reduces proportion of patients with cognitive impairment.
Conclusion
This study indicates that cognitive impairment may be an important sequela of COVID-19. Further research with adequate sample sizes is warranted regarding COVID-19’s association with new-onset dementia and dementia progression, and the effect of repeat infections. There is a need for development of diagnostic and management protocols for COVID-19 patients with cognitive impairment.
Introduction
As the population of older adults (aged ≥65 years) increases worldwide, the prevalence of dementia is expected to increase with significant implications for both health and social well-being (Lambert et al., 2014, Wolters and Ikram, 2018). Dementia is a progressive neurocognitive disorder, impacting memory, language, behavior, and daily activities, and is a major cause of disability, severely affecting the quality of life and the ability to live independently (Kivimäki and Singh-Manoux, 2018). Compounding these challenges is the coronavirus disease 2019 (COVID-19), which was declared a pandemic by the World Health Organization (WHO) in March 2020, and has profoundly impacted health, social dynamics, and economic conditions globally (Cucinotta and Vanelli, 2020). With limited research on the adverse impact of COVID-19 on cognition, no study has conclusively demonstrated the link between COVID-19 and the onset or progression of dementia (Hariyanto et al., 2021, Liu et al., 2020, Pyne and Brickman, 2021). Nevertheless, the intersection of dementia and the COVID-19 pandemic heightens morbidity and mortality in the aging population, exposing individuals to significant risks.
Multiple studies have shown that dementia is associated with increased risk of morbidity and mortality from COVID-19 infection, especially among older adults who live in residential care and/or have other comorbid medical conditions (Hariyanto et al., 2021, Liu et al., 2020, the Management Group of the EAN Dementia and Cognitive Disorders Scientific Panel, 2021, Saragih et al., 2021). Recent evidence shows a high prevalence of dementia among COVID-19 patients (Soto-Añari et al., 2021, Canevelli et al., 2020, Wang et al., 2023, Azarpazhooh et al., 2020). Concurrently, COVID-19 case fatality rate is significantly higher in older adults with dementia (McMichael et al., 2020, Hsu et al.,.). However, the association between COVID-19 and dementia has not yet been clearly evaluated from a global perspective. The highlights the vulnerability of individuals with dementia and underscores the importance of investigating all potential impacts of COVID-19 including cognitive impairment.
COVID-19 and dementia share several risk factors, including age, obesity, cerebrovascular disease, and diabetes (NCIRD, 2023, Chen et al., 2009). COVID-19 can cause direct acute neurological effects, such as viral encephalitis, indicating that the SARS-CoV-2 virus can target the central nervous system (CNS) and exacerbate immune and inflammatory reactions, leading to direct brain effects (Wood, 2020, Iadecola et al., 2020). COVID-19 may also affect the brain indirectly, through long-term effects such as prolonged inflammation and cerebrovascular sequelae, such as stroke, both of which are risk factors for dementia onset and cognitive impairment (The Lancet, 2021, Maiese et al., 2021). COVID-19 also has been shown to result in altered amyloid processing in the brain, with pathological changes similar to Alzheimer’s disease (Ziff et al., 2022, Furman et al., 2023). However, only a few studies have explored the impacts of COVID-19 on dementia outcomes, such as the risk of new-onset dementia or the deterioration of cognitive function in patients with or without pre-existing dementia. Among those studies that have delved into these aspects, the findings indicate an association between COVID-19 and elevated risk of long-term cognitive decline, affecting individuals both with and without dementia (Wang et al., 2021). A recent systematic review conducted by Rahmati et al. (2023) revealed an increased risk of new-onset dementia (HR 1.66, 95% CI [1.42–1.94]) among survivors of COVID-19 (Rahmati et al., 2023). The available evidence emphasizes the significant implications of COVID-19 on long-term cognitive outcomes, prompting continued efforts to deepen our understanding of the complex interplay between these two health challenges.
Identifying the link between COVID-19 and dementia onset or progression is crucial for understanding the impact of the pandemic on an existing high burden of disease caused by dementia. This knowledge is essential for tailoring effective healthcare strategies, optimizing diagnostic approaches, and developing targeted interventions to mitigate the impact of COVID-19 on cognitive health. The aim of this paper is to describe the impact of COVID-19 on cognition in COVID-19 patients with and without pre-existing dementia or cognitive impairment.
Section snippets
Study protocol
This review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines (PRISMA-P Group et al., 2015). The protocol for this review was recorded on the international prospective register of systematic reviews (PROSPERO) with the registration ID
CRD42023393486.
Search Strategy
The following databases were searched for articles pertaining to dementia/cognitive impairment and neuropsychological outcomes in COVID-19 patients: The Cochrane Central
Results
The sensitivity and specificity of each of the search strategies was found to be >75% when using relative recall. In total, 15,124 articles were identified by the search strategy. After eliminating duplicate titles and completing a review of article titles, abstracts and full-texts, 18 studies were included in the analysis (Fig. 1.). The demographics of the included studies are described in Table 1. The final pool of studies included 412,957 patients with COVID-19 (46.63% male) and 411,929
Discussion
We found that subacute and post-acute COVID-19 patients aged ≥65 years, most of whom were hospitalised for COVID-19, had evidence of cognitive impairment, with new-onset cognitive impairment accounting for more than 50%. These findings held true even when patients presenting with neurological symptoms in the acute phase of COVID-19 were excluded. In comparison, large population-based studies conducted before the COVID-19 pandemic in older adults without pre-existing cognitive impairment or
Conclusions
This study indicates an association between severe COVID-19 and cognitive impairment beyond the acute illness. Further research is necessary to elucidate the characteristics and pathogenesis of COVID-19 related cognitive impairment, the role of vaccination in preventing this and potential recovery over time. Vaccination reduces the risk of hospitalisation and of post-acute complications, and may be the major factor explaining the difference in risk of cognitive impairment in the early phase of
Declaration of interest
None
Funding
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors
Declaration of Competing Interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
