In a recent study published in Scientific Reports, researchers used the Australian Imaging Biomarkers and Lifestyle (AIBL) study data to investigate the risk of mild cognitive impairment (MCI) and Alzheimer's disease (AD) among cancer patients.
They also evaluated the cancer-related risk of cognition decay [i.e., cognitively unimpaired (CU) to mild cognitive impairment or Alzheimer's disease, and MCI to Alzheimer's disease].
Study: Exploring the association between cancer and cognitive impairment in the Australian Imaging Biomarkers and Lifestyle (AIBL) study. Image Credit: Orawan Pattarawimonchai/Shutterstock.com
Background
The relationship between cancer and AD is uncertain despite the well-established association between cancer and cognitive impairment. There is extensive research on the link between comorbidities and AD among AD patients.
However, most epidemiological research has focused on cancer risk after AD diagnosis or in cancer patients, with some showing cancer decreases AD incidence rates. Understanding these gaps will help develop innovative ways to address the cognitive decline in AD.
About the study
In the current study, researchers investigated the link between cancer and MCI/AD in AIBL patients.
The team used multivariate logistic regression modeling to determine the odds ratios (ORs) and risk ratios (RRs) for MCI/AD and cognitive decline between participants with and without cancer (C+ and C− participants, respectively), adjusting for potential confounders such as sex, education, apolipoprotein E (APOEε4) status, smoking habits, and alcohol intake.
They obtained blood samples from all subjects for apolipoprotein (APOE) testing and classified alcohol use as low (less than three days per week), moderate (three to six days per week), and excessive (daily).
All study participants had prior cancer diagnoses and self-reported their cancer history at recruitment and cancer occurrences during follow-up. From the 2,854 AIBL participants [1,187 (56%) females], the team excluded 718 from the present study due to unclear cancer or cognitive conditions at enrolment.
They categorized the remaining individuals into the cognitively unimpaired, mild cognitive impairment, Alzheimer’s disease, and cognition category progressing (PRO) groups.
The team allocated individuals classified as cognitively unimpaired or those with mild cognitive impairment undergoing cognition category changes at follow-up (cognitively unimpaired to mild cognitive impairment or Alzheimer’s disease, or mild cognitive impairment to Alzheimer’s disease) to the cognition category progression group.
The researchers compared the change in Clinical Dementia Rating Scale Sum of Boxes scores with time (ΔCDR-SOB, a proxy for cognitive loss) among C+ and C- individuals.
Neurologists and neuropsychologists evaluated cognition using amyloid positron emission tomography (PET) and neuropsychology evaluations.
Results
The study included 2,136 participants: 61% (n=1,297) CU, 10% (n=217) MCI, 17% (n=369) AD, and 12% (n=253) PRO. Among the participants, 74% were C- and 26% were C+.
The C+ group had a 37% lower chance of Alzheimer's disease (AD), a 27% and 31% lower overall risk of MCI and AD, and a 59% lower rate of cognition deterioration from MCI to AD.
Of 217 individuals with mild cognitive impairment, 47 (22%) had cancer. The crude logistic regressions showed that C+ individuals had 0.7-fold lower chances of MCI than C- participants.
Even after controlling for sex, APOE ε4, and smoking, the relationship between cancer prevalence and mild cognitive impairment remained strong. However, after accounting for all variables, the correlation became statistically insignificant.
After confounder adjustment, the team found no statistically significant inverse correlations between cancer prevalence and mild cognitive impairment. Among 369 AD patients, 73 (20%) had cancer.
The crude regressions showed cancer-related to a 40% decreased risk of Alzheimer's disease (OR, 0.6). Controlling for all variables, C+ individuals had a 0.6-fold lower risk of developing Alzheimer's disease than C- participants.
C+ individuals had significantly lower MCI (risk ratio, 0.7) and Alzheimer’s disease risks (RR, 0.7) than C- groups. Male C+ individuals showed a significant risk decrease for MCI (OR, 0.6) and AD (OR, 0.7) than male C− ones.
However, only AD but not MCI risk significantly reduced among female C+ individuals than their C- counterparts.
C+ individuals with APOE ε4 alleles had statistically significant risk decreases for AD (OR, 0.7) but not for MCI than C- participants. Neither crude nor adjusted models revealed a significant correlation between cancers and cognitive decay among PRO individuals. Among the participants, 88 cognitively unimpaired individuals progressed to the MCI group, with 25% scoring C+.
The unadjusted and adjusted logistic regressions found no statistically significant association between cancer diagnosis and MCI development. In the same analysis, 15 (16%) individuals who advanced from mild cognitive impairment to Alzheimer’s disease (n=95) scored C+.
The risk decreases of cognition deterioration in C+ subjects were non-significant; however, the relationship between cancer history and mild cognitive impairment to Alzheimer’s disease progression.
A higher score indicated more severe cognitive impairment. The ΔCDR-SOB score was 0.3 and 0.6 units/year for C+ and C- participants, respectively.
Conclusion
Overall, the study findings showed inverse relationships between cancer, Alzheimer's disease, and cognitive impairment in AIBL patients.
Cognition deterioration was slower in C+ individuals. Future research should examine MCI to reduce disease heterogeneity, evaluating brain levels of amyloid-beta.
Pathobiological mechanisms, including p53 gene alterations, Aβ buildup, tau hyperphosphorylation, oncogenic molecules, and P-glycoprotein at the blood-brain barrier, may explain the inverse relationship between cancer history and Alzheimer's disease.
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