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This study assessed whether the effect of vascular risk on cerebral blood flow (CBF) varies by gene dose of apolipoprotein (APOE) ε4 alleles. 144 older adults without dementia from the Alzheimers Disease Neuroimaging Initiative underwent arterial spin labeling and T1-weighted MRI, APOE genotyping, fluorodeoxyglucose positron emission tomography (FDG-PET), lumbar puncture, and blood pressure (BP) assessment. Vascular risk was assessed using pulse pressure (systolic BP - diastolic BP). CBF was examined in six AD-vulnerable regions: entorhinal cortex, hippocampus, inferior temporal cortex, inferior parietal cortex, rostral middle frontal gyrus, and medial orbitofrontal cortex. Linear regressions tested the interaction between APOE ε4 dose and pulse pressure on CBF in each region, adjusting for age, sex, cognitive classification, antihypertensive medication use, FDG-PET, reference CBF region, and AD biomarker positivity. There was a significant interaction between pulse pressure and APOE ɛ4 dose on CBF in the entorhinal cortex, hippocampus, and inferior parietal cortex, such that higher pulse pressure was associated with lower CBF only among ε4 homozygous participants. These findings demonstrate that the association between pulse pressure and regional CBF differs by APOE ε4 dose, suggesting that targeting modifiable vascular risk factors may be particularly important for those genetically at risk for AD.

IntroductionOlder adults living with Alzheimer's disease and related dementias (ADRD) who are then diagnosed with cancer are an understudied population. While the role of cognitive impairment during and after cancer treatment have been well-studied, less is understood about patients who are living with ADRD and then develop cancer. The purpose of this study is to contribute evidence about our understanding of this vulnerable population.Materials and methodsThis was a retrospective cohort study of a linked, representative family of databases of cancer registries and Medicare administrative claims that make up the SEER-Medicare database. Older adults ages 68 and older with a first primary cancer type: breast, cervical, colorectal, lung, oral, or prostate were eligible for inclusion (N = 337,932). Prevalence estimates of ADRD across cancer types and a 5% non-cancer comparison sample were compared by patient factors.ResultsThe overall prevalence of patients who had an ADRD diagnosis anytime in the three years prior to their cancer diagnosis was 5.6%. Patients with ADRD were more likely to be female, older (over age 75), a racial/ethnic minority, single, with multiple chronic conditions, and a tumor diagnosed early (stage I) or were unstaged. Black patients with colorectal and oral cancer had the highest and second highest prevalence of ADRD compared to White patients (13.46% vs 7.95% and 12.64% vs 7.82% respectively, p  .0001).DiscussionThe higher prevalence of ADRD among Black and Latine older adults with cancer not only aligns with the trend observed in our non-cancer comparison sample, but also, these findings demonstrate the compounded risk experienced by minoritized older adults over the life course. The greater than expected prevalence of patients with ADRD who go on to develop cancer demonstrates better assessment of cognition is urgently needed. Accurate identification of these vulnerable populations is critical to improve assessment, care coordination, and address inequities in screening and treatment planning.