Cancer and risk of Alzheimer's disease: Small association in a nationwide cohort study

Ording, Anne Gulbech; Horváth‐Puhó, Erzsébet; Veres, Katalin; Glymour, M. Maria; Rørth, Mikael; Sørensen, Henrik Toft; Henderson, Victor W.

doi:10.1002/alz.12090

Cited by 33 publications

(41 citation statements)

References 36 publications

(75 reference statements)

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“…Our search returned 2764 unique records; 22 studies (19 cohort studies and 3 case-control studies) met the eligibility criteria and were included (eFigure 1 in the Supplement ). In total, 13 studies 10 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 investigated all cancer types (eTable 2 in the Supplement ); 5 studies 49 , 50 , 51 , 52 , 53 investigated prostate cancer; 3 studies 9 , 54 , 55 investigated NMSC; and 1 study 56 investigated breast cancer ( Table 1 ). Five studies that investigated all cancer types (5 of 13) additionally reported cancer type–specific subgroup analyses.…”

Section: Resultsmentioning

confidence: 99%

Association Between Alzheimer Disease and Cancer With Evaluation of Study Biases

et al. 2020

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Key Points Question Does an association exist between cancer and subsequent Alzheimer disease (AD), and how likely is it that such a finding is associated with methodological bias rather than with a true common etiology? Findings In this systematic review and meta-analysis of 22 cohort and case-control studies representing 9 630 435 individuals, cancer diagnosis was associated with 11% decreased incidence of AD. Bias-adjusted metaregressions suggested that competing risks and diagnostic bias were unlikely explanations for the observed association, whereas survival bias remains to be ruled out. Meaning The observed inverse association between cancer and AD does not seem to be a consequence of competing risks, known confounding, or diagnostic bias.

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Section: Resultsmentioning

confidence: 99%

Association Between Alzheimer Disease and Cancer With Evaluation of Study Biases

et al. 2020

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“…[1][2][3][4][5][6][7][8][9][10] Although some recent studies report smaller effect estimates, meta-analyses show that dementia incidence is 15% to 38% lower among those with history of cancer compared to those without. 1,[3][4][5][6][7]37 Some studies examining diverse site-specific cancers,…”

Section: Discussionmentioning

confidence: 99%

“…There is substantial literature on the inverse cancer‐dementia association 1–10 . Although some recent studies report smaller effect estimates, meta‐analyses show that dementia incidence is 15% to 38% lower among those with history of cancer compared to those without 1,3‐7,37 . Some studies examining diverse site‐specific cancers, including breast, colorectal, lung, and non‐melanoma skin cancers, show similar results 1,8,9,11,12 .…”

Section: Discussionmentioning

confidence: 99%

The competing risk of death and selective survival cannot fully explain the inverse cancer‐dementia association

Hayes‐Larson

Ackley

Zimmerman

et al. 2020

Alzheimer's & Dementia

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Introduction: We evaluated whether competing risk of death or selective survival could explain the reported inverse association between cancer history and dementia incidence (incidence rate ratio [IRR] ≈ 0.62-0.85). Methods: A multistate simulation model of a cancer-and dementia-free cohort of 65year-olds was parameterized with real-world data (cancer and dementia incidence, mortality), assuming no effect of cancer on dementia (true IRR = 1.00). To introduce competing risk of death, cancer history increased mortality. To introduce selective survival, we included a factor (prevalence ranging from 10% to 50%) that reduced cancer mortality and dementia incidence (IRRs ranged from 0.30 to 0.90). We calculated IRRs for cancer history on dementia incidence in the simulated cohorts. Results: Competing risk of death yielded unbiased cancer-dementia IRRs. With selective survival, bias was small (IRRs = 0.89 to 0.99), even under extreme scenarios. Discussion: The bias induced by selective survival in simulations was too small to explain the observed inverse cancer-dementia link, suggesting other mechanisms drive this association.

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“…However, contrary to general expectations, patients with cancer in some of these analyses demonstrated a decreased risk of dementia (summarized, e.g., in [ 4 ]). Other analyses reported that these inverse correlations between cancer and dementia might be restricted to specific etiologies such as Alzheimer’s disease and diminish over time, arguing that the association between cancer and general risk of dementia is limited [ 12 ]. Furthermore, other authors reported a positive association between tumor markers and dementia rates in cancer patients [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Cancer Patients Have an Increased Incidence of Dementia: A Retrospective Cohort Study of 185,736 Outpatients in Germany

Roderburg

Loosen

Kunstein

et al. 2021

Cancers

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Background: Cancer is the second leading cause of death worldwide and incidence rates for several tumor entities are rising. In addition to a high cancer-specific mortality rate, many cancer patients also suffer from additional comorbidities. Among these, several psychological morbidities have been extensively studied in the past, but findings on the association between cancer and dementia have remained conflicting. In the present study, we evaluated the possibility of an association between cancer and dementia. Methods: Based on data from the IQVIA Disease Analyzer database, a total of 92,868 cancer outpatients initially diagnosed between 2000 and 2018 were matched by age, gender, index year, and yearly consultation frequency to 92,868 individuals without cancer. Ten-year incidence rates of dementia were compared for the two cohorts. Results: The overall cumulative incidence of dementia was significantly higher in cancer patients (19.7%) than in non-cancer patients (16.7%, p < 0.001). Cox regression models confirmed that this association was significant for both male (HR: 1.35 [1.30–1.41], p < 0.001) and female (HR: 1.26 [1.21–1.31], p < 0.001) patients and was consistent among all age groups analyzed (65–70, 71–75, 76–80, 81–85, and >85 years). In addition, the association between cancer and dementia was significant for all cancer entities analyzed (skin, digestive organs, prostate, breast, urinary tract, lymphoid and hematopoietic tissue, and lung cancer) and most pronounced in patients with lung cancer (HR: 1.44 [1.28–1.62], p < 0.001). Conclusions: Our data provide strong evidence for an increased incidence of dementia in a large cohort of patients with different cancer entities, which should raise awareness of this important comorbidity in cancer patients.

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Cancer and risk of Alzheimer's disease: Small association in a nationwide cohort study

Cited by 33 publications

References 36 publications

Association Between Alzheimer Disease and Cancer With Evaluation of Study Biases

Association Between Alzheimer Disease and Cancer With Evaluation of Study Biases

The competing risk of death and selective survival cannot fully explain the inverse cancer‐dementia association

Cancer Patients Have an Increased Incidence of Dementia: A Retrospective Cohort Study of 185,736 Outpatients in Germany

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