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

Topic: Risk, prevention and care in population studies

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). Conclusions and Relevance: 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.

Key findings

• 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).

Why it matters

This study found that people with various clinical conditions had a higher short-term likelihood of being diagnosed with dementia, likely because they were more likely to be tested or seen by doctors. This detection bias means that studies using electronic health records may overestimate the link between certain exposures and dementia.

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Study details

• Study designcohort study
• Participants137
• Effect size53.8%; 57.1%
• Evidence strengthModerate

Read the original

• DOI: 10.1001/jamanetworkopen.2025.6637
• PubMed: 40266617
• Original source →
• Free full text: JAMA Network Open →

Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).

@article{wang2025-40266617,
  author  = {Wang, Jingxuan and Choi, Minhyuk and Buto, Peter T. and Kelly, John Daniel and La Joie, Renaud and Kornak, John and Zimmerman, Scott C. and Chen, Ruijia and others},
  title   = {{Detection Bias in EHR-Based Research on Clinical Exposures and Dementia}},
  journal = {JAMA Network Open},
  year    = {2025},
  doi     = {10.1001/jamanetworkopen.2025.6637},
  pmid    = {40266617},
  url     = {https://doi.org/10.1001/jamanetworkopen.2025.6637}
}

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• Association Between Age at Diabetes Onset and Subsequent Risk of Dementia JAMA · 2021-04-01 · usefulness score 77/100 · Risk factors
• Type 2 Diabetes as a Risk Factor for Dementia in Women Compared With Men: A Pooled Analysis of 2.3 Million People Comprising More Than 100,000 Cases of Dementia Diabetes Care · 2016-02 · usefulness score 76/100 · Prevention and risk
• Missed and delayed diagnosis of dementia in primary care: prevalence and contributing factors Alzheimer disease and associated disorders · 2009-10-01 · usefulness score 67/100 · Getting a diagnosis
• Associations between physical frailty and dementia incidence: a prospective study from UK Biobank The lancet. Healthy longevity · 2020-11-02 · usefulness score 58/100 · Prevention and risk
• A clinicopathological approach to the diagnosis of dementia Nature reviews. Neurology · 2017-07-14 · usefulness score 50/100 · Getting a diagnosis

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