Cardiovascular health, infection burden, and incident dementia in the UK Biobank

Abstract

Introduction: Among older adults, total and hospitalized infection may be associated with incidence of all-cause and Alzheimer's disease (AD) dementias, with variation by cardiovascular health (CVH).

Methods: We used Cox proportional hazards (PH) models to examine the relationships between International Classification of Diseases-10th revision (ICD-10)-specific viral and bacterial infectious agents and incident all-cause and AD dementia among 355,046 UK Biobank participants ≥50 years at baseline. Life's Essential 8 (LE8) index reflected CVH.

Results: In both sexes, total infection burden (yes vs. no) was associated with all-cause dementia, with significant interactions by LE8 tertiles, whereby this relationship was significant only in the lowest LE8 tertile. Hospital-treated infection burden (yes vs no) was significantly related to all-cause and AD dementia, with no significant interaction with LE8 tertile. Age group patterns were detected.

Discussion: AD and all-cause dementia were related to hospital-treated infections, while CVH modified the relationship of total infection burden with all-cause dementia. Highlights Secondary analysis on >355,000 UK Biobank participants ≥50 years at baseline. Alzheimer's disease and all-cause dementia are both related to hospital-treated infection. Cardiovascular health modifies association of infection burden with all-cause dementia.

Keywords: Alzheimer's disease; cardiovascular health; dementia; hospitalization; infection.

FIGURE 1.. Three-level infection burden vs. all-cause dementia, UK biobank 2006-2021

Abbreviations: chi2=chi-square test; CI=confidence interval; hosp=hospital-treated infection group; KM=Kaplan Meier; none=no infection group; nonhosp=non-hospital treated infection group; Pr=P-values; UK=United Kingdom. Note: Numbers at risk for each age interval is presented in the Table. Chi2 refers to a log-rank test. The original distribution of the three-level infection categorization was: 0: n=230,731 (no infections); 1: n=79,253 (non-hospital treated infections); 2: n=45,062 (hospital-treated infections) out of the total of 355,046. Details are provided on github: https://github.com/baydounm/UKB-paper3-supplementarydata.

FIGURE 2.. Volcano plot of odds of hospital-treated infections vs. non-hospital-treated infections by type of infection

Abbreviations: Ln=Log_e; OR=Odds Ratio. Note: Based on a series of age and sex-adjusted logistic regression models, with main predictor being the type of prevalent infection (1=yes, 0=no) and the outcome being hospital-treated vs. non-hospital-treated infection (1=yes, 0-no). The y-axis is the predictor’s associated p-value on a −Log10 scale and the X-axis is the Log_e(odds ratio) from the age and sex-adjusted logistic models for each predictor. A twofold increase or decreased odds of the infection being hospital-treated is marked by red and blue colors, respectively. Values of the odds ratio in between is marked by a black color. An estimate with an uncorrected p-value<0.05 is marked by the UKB field number (See UKB showcase URL: https://biobank.ndph.ox.ac.uk/showcase/ ), while a Bonferroni corrected p-value<0.00038 (132 estimates) is marked with a dashed line. All infections occurred prior to baseline assessment. Dot sizes are proportional to the largest of two prevalence proportions (hospitalized vs. non-hospitalized) for each infection type, using the formula dot size=1+log2(3*larger_of_two_means/avg_of_larger_than_two_means). Details are provided in supplementary datasheet 1 included on github: https://github.com/baydounm/UKB-paper3-supplementarydata.

FIGURE 3.. Graphical depiction of the study design