title: Extended Maternal and Paternal Hereditary Risk for Alzheimer’s Disease Examined by Sex in a Sample of Community Dwelling Older Adults in Cache County, Utah
Creators: name: Vernon, Elizabeth K.
Publisher: name: Utah State University
Year: 2021

description: More than 6 million Americans are living with Alzheimer’s Disease (AD) and this number is expected to rise and surpass 12.7million individuals by the year 2050. Currently there is no cure for the disease and prior research has focused on prevention by identifying risk factors. Known risk factors associated with AD include older age, female sex, genetics, family history of AD, genotype of the apolipoprotein E (APOE) gene, and vascular risk factors (e.g., cholesterol, hypertension) and conditions or events (e.g., CHF, stroke). The effects of many of the above risk factors have differed in men and women, but few studies have examined how family history of AD, direct maternal or paternal lineage of AD, parental longevity, and cardiovascular risk factors and conditions might influence risk for AD differently for men and women. This project analyzed existing data from a population-based longitudinal study, the Cache County Study on Memory in Aging (CCSMA), that included permanent residents of Cache County, Utah who were aged 65 years or older in 1995. The study’s data were enriched through additional data obtained for extended family history and Medicare claims and death certificates that were made available through data linkage with the Utah Population Database. The original study ran from 1995-2007, but with the additional Medicare claims and death certificates, identification of AD related outcomes and risk factors were extended to 2019. The aim of this current study was to examine whether the risk for AD differed between men and women with regards to family history of AD, maternal and paternal lineage of AD, longer-lived parents, and whether vascular health conditions affected these risks.
Results from this dissertation showed that having a first-degree relative (parents, siblings, or offspring) with AD increased the risk for AD in men by 58%, Odds Ratio (OR)= 1.58, p= .003, and women by 66%, OR= 1.66, p=< .001. Among women, direct maternal but not paternal lineage of AD was associated with a 56% increased risk for AD, OR= 1.56, p=.005, whereas in men, history of maternal or paternal lineage of AD(above age 87) did not affect their risk of developing AD. Having a longer-lived mother or longer-lived father was not associated with AD risk in women. However, men with a history of a longer-lived mother and who had an APOE Ɛ4 positive genotype had three times the risk of AD, OR= 3.15, p= .020. Men who had both a longer-lived mother and a longer-lived father compared to men without had an 11% reduction in risk for AD, OR= 0.89, p=.041. In relation to cardiovascular conditions and risk in women, those with a history of congestive heart failure (CHF) and a direct paternal lineage of AD had double the risk of AD compared to those without, though those women with no paternal lineage of AD were at an 11 times greater risk, OR= 11.15, p=< 0.001. For men there were no associations between family history of AD and cardiovascular conditions. Among both men and women, several cardiovascular risk factors increased risk for AD. For instance, men and women with a history of stroke or CHF had an increased risk for AD. Men with a history of hypertension and high cholesterol/triglycerides/atherosclerosis were also at increased risk of developing AD. Notably, women with a history of myocardial infarction had a reduction in risk.
Although this study is observational in nature and thus does not prove a direct causal relationship between familial history and AD, it does support previous research that found having a first-degree relative with AD regardless of sex increased the risk for AD. The study also highlighted the importance of studying risk factors like family history, separately for men and women. Thus, women with a maternal history of AD were at greater risk than those with a paternal history of AD, but no such association was found in men. Men were at slightly reduced risk for AD when having both longer-lived parents and there were slight differences by sex in cardiovascular risk factors that predicted risk for AD. The different results obtained for men and women have clinical implications in monitoring for AD risk in older adults and suggest aggressive treatment for vascular risk factors and conditions amongst women in particular, with CHF and family history. Further research is needed to understand the underlying mechanisms with how these risks vary in males and females.