38 Dementia, Apoe and COVID-19 Severity

Introduction During the COVID-19 pandemic, pre-existing dementia was associated with a 3x increase in risk of hospitalisation and (25 6%) of COVID-19 related deaths had dementia However, it is unclear whether people living with dementia are at higher risk of COVID-19 due to dementia or whether there may be a biologically plausible link between dementia and COVID-19 The ApoE e4 allele is highly associated with dementia We aimed to test the COVID-19 risk associated with dementia and the association between ApoE e4e4 allele and COVID-19 with the aim of clarifying biological vulnerability Methods UK Biobank (England) participants baseline (2006 to 2010), plus secondary care data to 2017 Separate analysis tested dementia and ApoE genotype association with COVID-19 status (16th March-31st May 2020) or mortality (to March 31, 2020, plus incomplete deaths from April, 2020) in logistic models, adjusted for demographics and technical covariates Results In 269,070 participants aged 65+, including 507(0 2%) hospitalized COVID-19 patients, those with pre-existing dementia were at increased risk of being hospitalized for COVID-19 (OR = 3 50 95% CI 1 93 to 6 34) and also for COVID-19 and death (OR = 7 30 95% CI 3 28–16 21) In 375,689 European-ancestry UKB participants, ApoE e4e4 homozygotes were more likely to be COVID-19 test positives (reaching genome-wide significance: OR = 2 24, 95% CI:1 72–2 93, p = 3 24 × 10–9) and of mortality with test-confirmed COVID-19 (OR = 4 29, 95% CI: 2 38–7 72, p = 1 22 × 10–6), compared to e3e3s homozygotes The associations were little changed in subsets of participants who were free of diseases associated with ApoE e4 and COVID-19 severity Conclusion Dementia was found to be disproportionally common in older adults who develop severe COVID-19 We have shown a plausible genetic pathway of increased COVID-19 risk with dementia, therefore suggesting that the positive association between dementia and COVID-19 is not just the result of high cases of COVID-19 in care homes