HDL-C & Glucose Levels Measured in Early to Mid-Adulthood Associated with Alzheimer Occurrence Decades Later

by | Jun 10, 2022 | 2022, Alzheimer's Disease, Blood Lipids, Blood Sugar, Brain Health

Written by Taylor Woosley, Staff Writer. Study findings show that elevated glucose levels (15 mg/dL increase) in middle adulthood was associated with a 14.5% increased risk of AD while increased high density lipoprotein cholesterol (15 mg/dL increase) was associated with a 15.4% decreased risk of AD in early adulthood and a 17.9% decreased risk in middle adulthood. 

Alzheimer's - Brain healthAccording to the World Health Organization, over 55 million people globally suffer from some form of dementia 1. Alzheimer’s disease (AD) is the most common type of dementia, accounting for 60-70% of the cases 2. AD is a chronic progressive neurodegenerative disorder and the presence of β-amyloid (Aβ) plaques, tau tangles, and oxidative stress are hallmark characteristics of the disease 3. Progression of AD leads to a decrease in neuronal activity, causing difficulties with cognition, loss of memory, and reasoning 4.

There is no current proven treatment to slow or reverse AD, making prevention and early detection an important step to lower the risk of AD-related complications and mortality. The pathogenesis of inflammatory disorders caused by oxidative stress is further worsened by excess levels of glucose or lipids 5. One neurodegenerative biomarker that has been studied for its potential influence on AD is abnormal glucose regulation 6. Elevated BMI and uncontrolled glucose levels are common metabolic dysfunctions noted in AD 7. Additionally, aberrant lipid metabolism is reported to be closely related to the development of neurodegenerative diseases 8.

Zhang et al. conducted a study to observe the influence of modifiable vascular risk factors using data from the Framingham Heart Study (FHS) Offspring Cohort, a longitudinal study focused on evaluating vascular health and cognitive decline. Participants (n=5124, mean age of 36 years) were examined on average every 4 years, including blood lipid fractions, total cholesterol, triglycerides, blood glucose, BMI, blood pressure, and smoking activity. At the second health examination (participant’s mean age of 44 years) subjects were assessed for cognitive impairment and incident dementia. At the fifth health examination, The Mini-Mental State Examination (MMSE) was administered to monitor changes in cognitive ability.

To evaluate the associations of vascular risk factors with incident AD, the Cox proportional hazards regression models were used to asses each risk factor measurement with AD occurrence. Additionally, Cox analyses further evaluated the association of risk factors with AD occurrence within three age ranges: early adulthood (ages 35-50), middle adulthood (ages 51-60), and late adulthood (ages 61-70). Significant findings of the FHS Offspring Cohort analysis are as follows:

  • Risk of AD incidence was inversely associated with HDL-C level measured at the first ([HR] = 0.87 [0.76-1.00] P = 0.045), second (HR = 0.83 [0.72-0.97], P = 0.016), sixth (HR = 0.82 [0.72-0.93], P = 0.0021), and seventh (HR = 0.79 [0.68-0.92], P = 0.0024) examinations.
  • Additionally, risk of AD incidence was associated with triglyceride levels measured at the first (HR = 1.34 [1.12-1.59] P = .0010), second (HR = 1.27 [1.10-1.47], P = 0.0014), fifth (HR = 1.19 [1.23-1.39], P = 0.024), sixth (HR = 1.20 [1.03-1.40], P = 0.022) and seventh (HR = 1.33 [1.10-1.59], P = 0.0027) examinations.
  • Blood glucose was significantly associated with AD occurrence at every exam (Exam1: HR = 1.12 [1.01–1.26], P = 0.041; Exam2: HR = 1.12 [1.04–1.20], P = 0.0020; Exam3: HR = 1.09 [1.01–1.16], P = 0.022; Exam4: HR = 1.11 [1.05–1.17], P = 0.00040; Exam5: HR = 1.07 [1.01–1.13], P = 0.020; Exam6: HR = 1.09 [1.03–1.15], P = 0.0041; Exam7: HR = 1.13 [1.05–1.12], P = 0.00060; Exam8: HR = 1.14 [1.04–1.26], P = 0.0058; Exam9: HR = 1.39 [1.06–1.82], P = 0.017).
  • Analysis by age group shows that a 15 mg/dL increase in HDL-C is associated with a 15.4% reduction in AD risk in early adulthood and a 17.9% reduction in AD risk in middle adulthood groups.
  • Analysis by age group shows that for every 15 mg/dL increase in blood glucose, risk of AD incidence increases by 14.5%.

In conclusion, vascular risk factor data and cognitive assessments provided from the FHS Offspring Cohort confirm the association of poor vascular health, particularly HDL and blood glucose levels, and increased risk of AD development. Limitations of the study include lack of racial diversity in subjects which limits the generalizability to other populations and the lack of lipid and glucose blood level data at the first two examinations.

Source:  Zhang, Xiaoling, Tong Tong, Andrew Chang, Ting Fang Alvin Ang, Qiushan Tao, Sanford Auerbach, Sherral Devine et al. “Midlife lipid and glucose levels are associated with Alzheimer’s disease.” Alzheimer’s & Dementia (2022).

© 2022 The Authors. Alzheimer’s & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer’s Association

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Taylor Woosley studied biology at Purdue University before becoming a 2016 graduate of Columbia College Chicago with a major in Writing. She currently resides in Glen Ellyn, IL.

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