Association between cancer and dementia risk in the UK Biobank: evidence of diagnostic bias

Wang, Jingxuan; Buto, Peter; Ackley, Sarah F.; Kobayashi, Lindsay C.; Graff, Rebecca E.; Zimmerman, Scott C.; Hayes-Larson, Eleanor; Mayeda, Elizabeth Rose; Asiimwe, Stephen B.; Calmasini, Camilla; Glymour, M. Maria

doi:10.1007/s10654-023-01036-x

Cited by 4 publications

(4 citation statements)

References 39 publications

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“…Although the inverse relationship between cancer and ADRD has been studied and reported in multiple epidemiological studies, 1 , 2 , 3 , 4 , 8 , 9 , 10 , 11 , 12 our results did not support an inverse link between cancer diagnosis and ADRD‐related neurodegeneration, except a small positive association between prostate cancer and total brain volume. Potential biases in observational studies may have yielded previously observed associations.…”

Section: Discussioncontrasting

confidence: 87%

“…ADRD cases were identified from linkage to hospital admission, primary care, and death records using a comprehensive list of ICD‐10 and ICD‐9 codes described elsewhere. 9 In brief, we included AD, vascular dementia, frontotemporal dementia, Lewy body dementia, alcohol‐related dementia, and Creutzfeldt‐Jakob disease. We defined ADRD onset as the first date of ADRD diagnosis.…”

Section: Methodsmentioning

confidence: 99%

“…Some studies have also found that individuals with a history of cancer had a lower neuropathologic burden of Alzheimer's disease (AD) compared to age‐matched decedents without a history of cancer 5–7 . Possible explanations for the observed inverse association include selective survival of healthier cancer survivors who are at lower risk of ADRD and shared biological or genetic mechanisms that elevate cancer risk but reduce ADRD risk 8–12 . The inverse association between cancer and ADRD has sparked substantial interest because biological explanations if validated, could offer important insights into the underlying biology of ADRD.…”

Section: Introductionmentioning

confidence: 99%

“… 5 , 6 , 7 Possible explanations for the observed inverse association include selective survival of healthier cancer survivors who are at lower risk of ADRD and shared biological or genetic mechanisms that elevate cancer risk but reduce ADRD risk. 8 , 9 , 10 , 11 , 12 The inverse association between cancer and ADRD has sparked substantial interest because biological explanations if validated, could offer important insights into the underlying biology of ADRD. While existing research has focused on incident ADRD or cognitive function as the outcome of interest, there is a lack of evidence on the relationship between cancer history and biomarkers of ADRD risk—although there is research on treatment‐induced structural and functional brain changes among breast cancer survivors, 13 , 14 , 15 only two prior studies have evaluated the association between cancer diagnosis and MRI markers of structural brain aging.…”

Section: Introductionmentioning

confidence: 99%

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Association of cancer history with structural brain aging markers of Alzheimer's disease and related dementias risk

Wang,

Sims,

Ackley

et al. 2023

Alzheimer's & Dementia

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INTRODUCTIONCancer survivors are less likely than comparably aged individuals without a cancer history to develop Alzheimer's disease and related dementias (ADRD).METHODSIn the UK Biobank, we investigated associations between cancer history and five structural magnetic resonance imaging (MRI) markers for ADRD risk, using linear mixed‐effects models to assess differences in mean values and quantile regression to examine whether associations varied across the distribution of MRI markers.RESULTSCancer history was associated with smaller mean hippocampal volume (b = ‐19 mm3, 95% CI = ‐36, ‐1) and lower mean cortical thickness in the Alzheimer's disease signature region (b = ‐0.004 mm, 95% CI = ‐0.007, ‐0.000). Quantile regressions indicated individuals most vulnerable to ADRD were more affected by cancer history.DISCUSSIONSome brain MRI markers associated with ADRD risk were elevated in adults with a history of cancer. The magnitude of the adverse associations varied across quantiles of neuroimaging markers, and the pattern suggests possible harmful associations for individuals already at high ADRD risk.HIGHLIGHTS We found no evidence of an inverse association between cancer history and ADRD‐related neurodegeneration. Cancer history was associated with smaller mean hippocampal volume and lower mean cortical thickness in the Alzheimer's disease signature region. Quantile regressions indicated individuals most vulnerable to ADRD were more affected by cancer history.

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Section: Discussioncontrasting

confidence: 87%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Association of cancer history with structural brain aging markers of Alzheimer's disease and related dementias risk

Wang,

Sims,

Ackley

et al. 2023

Alzheimer's & Dementia

Self Cite

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The inverse association between cancer history and incident cognitive impairment: Addressing attrition bias

Shardell,

Rathbun,

Gruber‐Baldini

et al. 2024

Alzheimer's & Dementia

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INTRODUCTIONCancer is inversely associated with cognitive impairment. Whether this is due to statistical handling of attrition (death and censoring) is unknown.METHODSWe quantified associations between cancer history and incident cognitive impairment among Health, Aging, and Body Composition Study participants without baseline cognitive impairment or stroke (n = 2604) using multiple competing‐risks models and their corresponding estimands: cause‐specific, subdistribution, and marginal hazards, plus composite‐outcome (cognitive impairment or all‐cause mortality) hazards. All‐cause mortality was also modeled.RESULTSAfter covariate adjustment (demographics, apolipoprotein E ε4, lifestyle, health conditions), cause‐specific and marginal hazard ratios (HRs) were similar to each other (≈ 0.84; P values < 0.05). The subdistribution HR was 0.764 (95% confidence interval [CI] = 0.645–0.906), and composite‐outcome Cox model HR was 1.149 (95% CI = 1.016–1.299). Cancer history was positively associated with all‐cause mortality (HR = 1.813; 95% CI = 1.525–2.156).DISCUSSIONCause‐specific, subdistribution, and marginal hazards models produced inverse associations between cancer and cognitive impairment. Competing risk models answer slightly different questions, and estimand choice influenced findings here.Highlights Cancer history is inversely associated with incident cognitive impairment. Findings were robust to handling of competing risks of death. All models also addressed possible informative censoring bias. Cancer history was associated with 16% lower hazard of cognitive impairment. Cancer history was associated with 81% higher all‐cause mortality hazard.

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Investigating the Role of Neighborhood Socioeconomic Status and Germline Genetics on Prostate Cancer Risk

Judd,

Spence,

Pritchard

et al. 2024

Preprint

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BackgroundGenetic factors play an important role in prostate cancer (PCa) development with polygenic risk scores (PRS) predicting disease risk across genetic ancestries. However, there are few convincing modifiable factors for PCa and little is known about their potential interaction with genetic risk. We analyzed incident PCa cases (n=6,155) and controls (n=98,257) of European and African ancestry from the UK Biobank (UKB) cohort to evaluate the role of neighborhood socioeconomic status (nSES)–and how it may interact with PRS–on PCa risk.MethodsWe evaluated a multi-ancestry PCa PRS containing 269 genetic variants to understand the association of germline genetics with PCa in UKB. Using the English Indices of Deprivation, a set of validated metrics that quantify lack of resources within geographical areas, we performed logistic regression to investigate the main effects and interactions between nSES deprivation, PCa PRS, and PCa.ResultsThe PCa PRS was strongly associated with PCa (OR=2.04; 95%CI=2.00-2.09; P<0.001). Additionally, nSES deprivation indices were inversely associated with PCa: employment (OR=0.91; 95%CI=0.86-0.96; P<0.001), education (OR=0.94; 95%CI=0.83-0.98; P<0.001), health (OR=0.91; 95%CI=0.86-0.96; P<0.001), and income (OR=0.91; 95%CI=0.86-0.96; P<0.001). The PRS effects showed little heterogeneity across nSES deprivation indices, except for the Townsend Index (P=0.03).ConclusionsWe reaffirmed genetics as a risk factor for PCa and identified nSES deprivation domains that influence PCa detection and are potentially correlated with environmental exposures that are a risk factor for PCa. These findings also suggest that nSES and genetic risk factors for PCa act independently.

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Association between cancer and dementia risk in the UK Biobank: evidence of diagnostic bias

Cited by 4 publications

References 39 publications

Association of cancer history with structural brain aging markers of Alzheimer's disease and related dementias risk

Association of cancer history with structural brain aging markers of Alzheimer's disease and related dementias risk

The inverse association between cancer history and incident cognitive impairment: Addressing attrition bias

Investigating the Role of Neighborhood Socioeconomic Status and Germline Genetics on Prostate Cancer Risk

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