Detection Bias in EHR-Based Research on Clinical Exposures and Dementia

Detection bias occurs when an exposure is associated with a systematic difference in outcome ascertainment or diagnosis. For dementia research, diagnosed health conditions that bring patients into frequent interaction with health care may increase the chance that an individual receives a dementia diagnosis.

To evaluate potential detection bias or misdiagnosis bias in evaluation of clinical factors associated with dementia using electronic health record (EHR) data.

This prospective cohort study used data from 2 population-based volunteer cohorts: UK Biobank (UKB) and All of Us (AOU). Participants were aged 55 years or older, were dementia-free at baseline, and had linked EHRs. Participants in UKB were followed up from baseline (2006-2010) until December 2022, and in AOU, from baseline (2017-2022) until July 2022. Data were analyzed from November 2023 through February 2025.

Diagnoses of type 2 diabetes, depression, hypertension, urinary tract infection, kidney stones, forearm fracture, and gastrointestinal (GI) bleeding.

Rate of incident all-cause dementia diagnosis from EHRs and associations between clinical exposures and incident dementia diagnosis, assessed using Cox proportional hazards regression models.

Among 228 392 participants from UKB (n = 137 374; mean [SD] age at baseline, 62.5 [4.1] years; 53.8% female) and AOU (n = 91 018; mean [SD] age at baseline, 66.9 [7.8] years; 57.1% female), those with a history of a clinical exposure at baseline had higher dementia incidence rates compared with those without such history. For example, among participants with a history of GI bleeding, the dementia incidence rates were 3.0 (UKB) and 7.7 (AOU) per 1000 person-years compared with 2.2 (UKB) and 2.4 (AOU) per 1000 person-years among those without a history of GI bleeding. All exposures were significantly associated with incident dementia, with hazard ratios (HRs) ranging from 1.18 (95% CI, 1.00-1.40) to 3.51 (95% CI, 3.08-4.01). Risk of incident dementia was typically highest in the first year following exposure diagnosis and attenuated thereafter. For example, in the first year after GI bleeding, there were larger elevations in risk of incident dementia (HR, 2.17 [95% CI, 1.46-3.22] in UKB; HR, 2.56 [95% CI, 1.62-4.04] in AOU) compared with 1 to 5 years after bleeding (HR, 1.46 [95% CI, 1.15-1.86] in UKB; HR, 2.14 [95% CI, 1.63-2.81] in AOU).

In this cohort study of 2 large datasets, diagnoses of several conditions associated with varying risks of dementia were associated with a higher short-term likelihood of dementia diagnosis. This finding suggests that diagnostic bias or misdiagnoses may lead to spurious associations between conditions requiring clinical care and subsequent dementia diagnoses.