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Cited by 425Dementia and Cognitive Impairment ResearchCancer-related cognitive impairment studiesAlzheimer's disease research and treatments

Inverse association between cancer and Alzheimer's disease: results from the Framingham Heart Study

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Driver, J. A., Beiser, A., Au, R., Kreger, B. E., Splansky, G. L., Kurth, T., Kiel, D. P., Lu, K. P. +2 more·2012·BMJ
DOI 10.1136/bmj.e1442PMC PMC3647385
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Abstract

OBJECTIVES: To relate cancer since entry into the Framingham Heart Study with the risk of incident Alzheimer's disease and to estimate the risk of incident cancer among participants with and without Alzheimer's disease. DESIGN: Community based prospective cohort study; nested age and sex matched case-control study. SETTING: Framingham Heart Study, USA. PARTICIPANTS: 1278 participants with and without a history of cancer who were aged 65 or more and free of dementia at baseline (1986-90). MAIN OUTCOME MEASURES: Hazard ratios and 95% confidence intervals for the risks of Alzheimer's disease and cancer. RESULTS: Over a mean follow-up of 10 years, 221 cases of probable Alzheimer's disease were diagnosed. Cancer survivors had a lower risk of probable Alzheimer's disease (hazard ratio 0.67, 95% confidence interval 0.47 to 0.97), adjusted for age, sex, and smoking. The risk was lower among survivors of smoking related cancers (0.26, 0.08 to 0.82) than among survivors of non-smoking related cancers (0.82, 0.57 to 1.19). In contrast with their decreased risk of Alzheimer's disease, survivors of smoking related cancer had a substantially increased risk of stroke (2.18, 1.29 to 3.68). In the nested case-control analysis, participants with probable Alzheimer's disease had a lower risk of subsequent cancer (0.39, 0.26 to 0.58) than reference participants, as did participants with any Alzheimer's disease (0.38) and any dementia (0.44). CONCLUSIONS: Cancer survivors had a lower risk of Alzheimer's disease than those without cancer, and patients with Alzheimer's disease had a lower risk of incident cancer. The risk of Alzheimer's disease was lowest in survivors of smoking related cancers, and was not primarily explained by survival bias. This pattern for cancer is similar to that seen in Parkinson's disease and suggests an inverse association between cancer and neurodegeneration.

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  • AD patients have a decreased incidence of cancer, with up to a 50% decrease reported.

    “Alzheimer’s disease (AD) patients have a decreased incidence of cancer.”

    From Alzheimer's Disease–Associated Amyloid-β Precursor Protein Prevents Aging Stress–Induced Mitophagy and Fumarate Depletion to Improve Antitumor Immunity (2025) · cites this paper as [1]

    The Results (Incident Alzheimer’s disease and risk of cancer) report a lower risk of subsequent cancer among participants with probable Alzheimer’s disease, supporting the printed citing sentence. The added claim of a decrease of ‘up to 50%’ does not match the reported estimate: the risk ratio was 0.39, corresponding to a 61% decrease. (LLM, conf=0.85)

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  • Apparent protective associations with AD may in part reflect competing risks, recruiting bias, or survivor bias in populations with elevated vascular morbidity.

    “Apparent protective associations with AD may, in part, reflect competing risks, recruiting bias, or survivor bias in populations with elevated vascular morbidity [18,19].”

    From Clonal Hematopoiesis of Indeterminate Potential as an Emerging Interdisciplinary Risk Factor in Alzheimer’s Disease: Current Evidence and Future Directions (2026) · cites this paper as [18]

    The Discussion (Strengths and limitations; page unavailable) acknowledges that participants with long follow-up are a selected population and that survival bias cannot be fully excluded. But it says the observed inverse association was not primarily due to survival bias during follow-up. The paper does not specifically attribute the association to competing risks or recruitment bias in populations with elevated vascular morbidity. (LLM, conf=0.84)

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Authors
Driver, J. A., Beiser, A., Au, R., Kreger, B. E., Splansky, G. L., Kurth, T., Kiel, D. P., Lu, K. P., Seshadri, S., & Wolf, P. A.
Affiliations
  • Brigham and Women's Hospital (US)
  • Boston University (US)
  • National Heart, Lung, and Blood Institute (US)
  • Beth Israel Deaconess Medical Center (US)
Corresponding author
Driver, J. A.
ORCID
Venue
BMJ
Publisher
BMJ
Published
2012-03-12
Volume
344
Issue
mar12 1
Pages
e1442-e1442
ISSN
  • 0007-1447 (ISSN-L)
  • 0959-8138
  • 1468-5833
DOI
10.1136/bmj.e1442
PMC
PMC3647385
OpenAlex
W2106285225
Cited by
425
References
4
Citations by year
2026: 23 · 2025: 32 · 2024: 36 · 2023: 29 · 2022: 23 · 2021: 42 · 2020: 32 · 2019: 26 · 2018: 38 · 2017: 32 · 2016: 20 · 2015: 18 · 2014: 34 · 2013: 29 · 2012: 9
FWCI
20.56
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • BMJ (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
Funders
  • National Institutes of Health (n01hc25195-41-0-1)
  • National Institute on Aging (AG-16495, AG08122, R01AG016495, R01AG008122)
  • National Heart, Lung, and Blood Institute (N01‐HC25195, AG08122, N01-HC-025195, AG16495)
  • National Institute of Neurological Disorders and Stroke (NS17950, R01NS017950)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cancer-related cognitive impairment studies
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Keywords
Alzheimer's disease, cancer, cancer survivors, tobacco-related cancer, stroke risk, dementia, neurodegeneration, cancer incidence, survivorship bias, Parkinson's disease
MeSH terms
Age Factors, Aged, Aged, 80 and over, Alzheimer Disease, Female, Humans, Male, Neoplasms, Risk Factors, Sex Factors, Smoking, Cohort Studies, Incidence, Survival Rate, Confidence Intervals, Proportional Hazards Models, Case-Control Studies

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