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. 2020 Sep 18;15(9):e0237676. doi: 10.1371/journal.pone.0237676

Table 3. Sensitivity analysis: Adjusted hazard ratios of developing dementia for varying time points following PPI Index date compared to unexposed controls.

Whole cohort
Including all dementia cases (n = 37,148) Including dementia cases (n = 13,484) diagnosed 2 to 5 years post-index date Including dementia cases (n = 9,822) diagnosed 5–9 years post-index date Including dementia cases (n = 4,594) diagnosed 10 years or more post-index date
36% of all dementia cases 26.4% of all dementia cases 12.4% of all dementia cases
HR 95% CI HR 95% CI HR 95% CI HR 95% CI
PPI 0.67 0.65 to 0.69* 0.58 0.56 to 0.60* 0.46 0.46 to 0.48* 0.29 0.28 to 0.30*
Age 1.05 1.05 to 1.06* 1.05 1.05 to 1.06* 1.06 1.05 to 1.06* 1.06 1.06 to 1.06*
Drink alcohol 1.10 1.01 to 1.18* 1.20 1.13 to 1.28* 1.18 1.10 to 1.25* 1.15 1.07 to 1.24*
Smoker 0.89 0.85 to 0.92* 0.89 0.86 to 0.92* 0.90 0.87 to 0.94* 0.91 0.87 to 0.95*
BMI 0.95 0.95 to 0.95* 0.95 0.95 to 0.95* 0.95 0.95 to 0.95* 0.95 0.95 to 0.95*
Diabetes 1.18 1.14 to 1.22* 1.18 1.14 to 1.23* 1.18 1.14 to 1.22* 1.18 1.13 to 1.23*
Cardiovascular disease 0.93 0.90 to 0.97* 0.94 0.91 to 0.98* 0.95 0.92 to 0.98* 0.95 0.92 to 0.99*
Depression 1.19 1.16 to 1.23* 1.19 1.15 to 1.24* 1.20 1.15 to 1.24* 1.17 1.12 to 1.21*
Head injury 1.49 1.43 to 1.56* 1.50 1.43 to 1.57* 1.51 1.43 to 1.59* 1.53 1.44 to 1.62*
Vitamin-B12 Deficiency 1.37 1.21 to 1.56* 1.42 1.25 to 1.61* 1.41 1.23 to 1.62* 1.44 1.23 to 1.69*
Anxiolytics 1.62 1.57 to 1.67* 1.65 1.60 to 1.70* 1.69 1.63 to 1.74* 1.77 1.70 to 1.84*
Antidepressants 1.66 1.61 to 1.72* 1.68 1.62 to 1.74* 1.68 1.61 to 1.74* 1.70 1.63 to 1.78*
Anticoagulants 0.87 0.84 to 0.91* 0.88 0.85 to 0.92* 0.88 0.84 to 0.92* 0.89 0.84 to 0.93*
Antiplatelets 1.72 1.66 to 1.79* 1.72 1.66 to 1.79* 1.73 1.66 to 1.80* 1.70 1.63 to 1.78*
Statins 0.86 0.83 to 0.89* 0.86 0.83 to 0.94* 0.87 0.83 to 0.90* 0.85 0.82 to 0.89*
Hormone replacement therapy 0.89 0.83 to 0.89* 0.89 0.84 to 0.94* 0.91 0.86 to 0.96* 0.96 0.90 to 1.02
Vitamin-B12 Medication 1.37 1.34 to 1.48* 1.44 1.37 to 1.52* 1.44 1.36 to 1.53* 1.46 1.36 to 1.56*
Anaemia Medication 1.09 1.06 to 1.13* 1.10 1.07 to 1.14* 1.11 1.07 to 1.15* 1.12 1.07 to 1.16*
Antihypertensives 0.71 0.69 to 0.73* 0.71 0.69 to 0.74* 0.71 0.68 to 0.73* 0.69 0.66 to 0.72*
Histamine Receptor-2 Medication 0.91 0.88 to 0.95* 0.97 0.93 to 1.01 1.04 1.0 to 1.09* 1.01 1.03 to 1.06*

*P < 0.05.

9,248 (24.9%) dementia cases were removed from this analysis as they developed dementia within two years of the PPI date. Gender, Anaemia and alcohol use were included in the model, but removed as did not reach statistical significance.