Alzheimer’s Associated With Reduced Cancer Risk; AD Risk Less in Some Cancer Patients

Pam Harrison

September 18, 2010

December 23, 2009 — Patients with Alzheimer’s disease (AD) are significantly less likely to develop cancer over time, whereas white patients with cancer have a lower risk of developing AD, according to a large, prospective cohort study. The study's findings, however, apply only to AD and not vascular dementia (VaD).

The study was published online December 23 and will appear in the January 12 issue of Neurology.

Cathy Roe, PhD, from the Washington University School of Medicine, St. Louis, Missouri, and multicenter colleagues found that the presence of any AD — either pure or mixed AD/VaD — was associated with an almost 60% reduction in future cancer hospitalization after adjusting for all relevant covariates. Prevalent cancer in the same cohort was associated with a 28% reduced risk of any AD and a 43% reduced risk of pure AD among white subjects, again after adjusting for all relevant confounders.

Interestingly, the opposite association between cancer and reduced risk of AD was observed in minority subjects, although the sample sizes were too small for stable estimates, the authors note.

"With both AD and cancer you have abnormal cell growth — one resulting in excessive cell death and the other out-of-control cell growth — and basic science suggests that the same molecular pathways may be involved in both," Dr. Roe told Medscape Neurology. "If one pathway is out of whack in one direction it leads to AD, and if it is out of whack in another direction, it gives you cancer. This is one possible explanation for this association."

Cognition Substudy of the CHS

For their analyses, study authors used data from the Cognition Substudy of the Cardiovascular Health Study (CHS) to investigate associations between cancer and 2 types of dementia with different origins — AD, which is related to neurodegenerative processes, and VaD, which is related to cerebrovascular insults. Participants were 65 years and older and had undergone magnetic resonance imaging and annual brief cognitive testing for up to 5 years. The cohort was followed up for a mean of 5.4 years for dementia and a mean of 8.3 years for cancer. At the study outset, 5.4% of the cohort had been diagnosed as having AD and 17.3% had been diagnosed as having cancer.

"In 3020 eligible participants, there were 478 new dementia diagnoses and 376 hospitalizations for invasive cancer over the follow-up period," investigators report. For participants with AD at study onset, the risk of future cancer hospitalization was reduced by 69% compared with those who did not have AD when the study started, after adjustment for sex, race, education, age, smoking, and weight.

For white patients who had cancer at the study outset, the risk of developing AD during follow-up was reduced by 43% compared with those who did not have cancer at baseline. "The effect was in the opposite direction for minorities, but the number of minority participants with a history of cancer was small (n = 29)," the authors observe.

Cancer history was also not associated with time to diagnosis of any VaD, pure VaD, or mixed dementia.

Table. Time to First Cancer Hospitalization by Dementia Diagnosis vs No Dementia at Baseline

Predictor No Dementia,
No.
Dementia Diagnosis,
No.
HR (95% CI) P Value
Pure AD 2107 71 0.31 (0.12 – 0.86) .237
Any AD (pure AD
and mixed AD/VaD)
2107 118 0.41 (0.20 – 0.84) .0145
Mixed AD/VaD 2107 47 0.58 (0.21 – 1.56) .2765
Any VaD (pure VaD
and mixed AD/VaD)
2107 76 0.89 (0.45 – 1.77) .7441
Pure VaD 2107 29 1.64 (0.66 – 4.11) .2885
Any dementia diagnosis 2107 165 0.70 (0.42 – 1.17) .1730

AD = Alzheimer's disease; CI = confidence interval; HR = hazard ratio; VaD = vascular dementia

VaD at Baseline

As the authors discuss, inclusion of participants with VaD at baseline allowed them to investigate whether those with AD had a reduced rate of incident cancer because they died earlier during the follow-up period than those without dementia. Previous research in the CHS sample indicated that patients with VaD have a shorter interval between disease onset and death than those with AD.

"Likewise, we found that the time between baseline assessment and death was faster for those with VaD compared to those with AD, with both dementia groups dying at a faster rate than participants without dementia in this study," the authors write.

However, as they point out, had the association of baseline AD and incident cancer been due to an earlier rate of death for the AD group vs those without dementia, "then a similar effect should have been found for the VaD group," they note. Similarly, no association between cancer history and the development of VaD was found.

"These results suggest that the development of many cancers may be inversely associated with the development of neurodegenerative disorder," Dr. Roe adds, "and ultimately, if these findings are replicated, it'll tell us more about the causes of these diseases and point out novel mechanisms to look at and new avenues of treatment."

Study Limitations

In an accompanying editorial, David Bennett, MD, and Sue Leurgans, PhD, Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois, thought that the study had a number of limitations, including the fact that investigators used hospital records to identify incident cancer cases. As they write, "patients with dementia tend to be diagnosed with cancer at a later stage, have significantly higher cancer mortality rates, and may not be hospitalized as frequently for cancer relative to those without dementia." All of these factors could lead to the appearance of a reduced incidence of cancer among those with dementia, they add.

They also suggest that treating cancer-free mortality among participants with dementia and dementia-free mortality among those with cancer as censoring events in a conventional Cox proportional hazards model has the potential to "markedly underestimate" the association between these conditions, giving the appearance of protective effects.

Still, they acknowledge that the study has many strengths and associations worthy of exploration in other cohorts and that the identification of molecular mechanisms linking cancer and AD "may lead to novel therapeutic targets and interventions."

The study was supported by the National Institutes of Health, the National Heart, Lung, and Blood Institute, the National Institute of Neurological Disorders and Stroke, the National Institute on Aging, the National Center for Research Resources, and the Washington University Alzheimer's Disease Research Center. Dr. Bennett serves on the editorial board of Neurology and has served or serves as a consultant to Abbott, Krog and Partners, Navigant Consulting Inc, Partner Fund Management LP, MFS Investment Management, UBS Global Asset Management, Schering Plough Corp, Double Helix Development, Medivation Inc, and Olson Research Group. He has also received research support from Danone Inc and the National Institutes of Health.

Neurology. Published online December 23, 2009.

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