BACKGROUND: The prevalence of Alzheimer’s disease (AD) and other types of dementia is expected to drastically increase between now and midcentury because of the aging baby boomer population. It is projected that by 2030, 74 million people aged 65 and older will comprise nearly 20% of the population (United States Census Bureau, 2017). By 2060, it is estimated that about 13.8 million people will have AD. In 2020, the estimated total health care costs for treating individuals with AD in 2020 is $305 billion (Wong, 2020). As the population ages, the cost is expected to increase to more than $1 trillion. This significant economic and health care burden could be greatly alleviated by the development of a treatment that would delay the onset of the disease or prevent the disease altogether. Increasing evidence supports cardiovascular health being linked to the health of the brain. Diabetes is a particular risk factor that increases the likelihood of cardiovascular disease and is consequently associated with a higher risk of developing AD and other dementias.
AIM: The aim of this study was to determine the association between persistent high blood glucose during midlife to late life and the risk of incident dementia and AD.
METHODS: This study included 1287 Framingham Offspring participants (669 women, mean age 68.6 ± 5.7 years) who were free of dementia and attended 5 consecutive examinations at 4-year intervals starting at midlife (Exam 3: 1983–1987, mean age 54.6 ± 5.8 years) until late life (Exam 7: 1998–2001, mean age 68.6 ± 5.7 years). These participants were subsequently followed up for incident dementia after a period of time (mean 14 ± 4.5 years). Based on the resulting data, this study examined the effect of midlife diabetes (fasting blood glucose level ≥ 126 mg/dL), late-life diabetes, 10-mg/dL incremental increases in fasting blood glucose (FBG), persistence of diabetes during midlife to late life, and a steep increase in FBG from midlife to late life over an 18-year exposure period. Further stratified analysis was completed on a subgroup of participants with a steep incline in FBG to determine if there was an interaction effect with apolipoprotein E4 (APOE4) carrier status.
RESULTS: During the follow-up period, 172 participants developed dementia, and of these cases, 135 participants had AD. Multivariable Cox proportional hazards models showed that persistent high FBG was associated with greater than 2-fold increase in risk of both incident dementia (hazard ratio [HR] 2.13, 95% confidence interval [CI] 1.37-3.33) and AD ([HR] 2.18, 95% [CI] 1.33-3.57) after adjusting for age, sex, education, APOE4, prevalent cardiovascular disease (CVD), and midlife diabetes treatment. In addition, individuals who experienced a steep increase in their FBG from Exam 3 to Exam 7 were associated with an increased risk of developing AD (p value = 0.022). Further stratification by APOE4 carrier status with a steep increase in FBG revealed that APOE4 non-carriers were associated with an approximate 2-fold increased risk for developing incident dementia ([HR] 1.90, 95% [CI] 1.12-3.16; p value < 0.05) and AD ([HR] 2.30, 95% [CI] 1.28-4.06; p value < 0.05).
CONCLUSIONS: Persistent high blood glucose was associated with an increased risk for developing incident dementia and AD in a community-based cohort. A steep increase in FBG during midlife to late life also increased the risk for developing dementia and AD in this cohort. These data support the potential of sustained cognitive benefits from lower blood glucose levels in midlife but also suggest that sharp increases in blood glucose levels in older adults may be a risk marker for dementia and AD.
| Identifer | oai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/43375 |
| Date | 17 November 2021 |
| Creators | Goodfellow, Grace |
| Contributors | Au, Rhoda |
| Source Sets | Boston University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
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