Blood Profile at Age 35 Linked to Subsequent Alzheimer’s Dementia

High-density lipoprotein (HDL) cholesterol and triglyceride levels in people as young as age 35 were linked with Alzheimer’s dementia decades later in life, longitudinal data from the Framingham Heart Study showed.

Risk of Alzheimer’s dementia fell by 15.4% during early adulthood (ages 35 to 50) and by 17.8% during middle adulthood (ages 51 to 60) for every 15 mg/dL increase in HDL cholesterol, reported Xiaoling Zhang, MD, PhD, of Boston University School of Medicine, and co-authors in Alzheimer’s & Dementia.

A 15 mg/dL increase in blood glucose measured during middle adulthood was associated with a 14.5% increased Alzheimer’s risk, they added. Triglyceride levels were associated with Alzheimer’s only in the early adulthood group. Findings remained significant after adjusting for treatment.

“These findings show for the first time that cardiovascular risk factors, including HDL, which has not been consistently reported as a strong risk factor for Alzheimer’s disease, contribute to future risk of Alzheimer’s disease starting as early as age 35,” Zhang said in a statement.

“While our findings confirm other studies that linked cholesterol and glucose levels measured in blood with future risk of Alzheimer’s disease, we have shown for the first time that these associations extend much earlier in life than previously thought,” added co-author Lindsay Farrer, PhD, also of Boston University.

The researchers looked at the influence of vascular risk factors on incident Alzheimer’s dementia over time among Framingham Heart Study Offspring participants, a group that’s been evaluated since 1971. Data on lipid fractions, glucose, blood pressure, BMI, and smoking were obtained prospectively from participants across nine quadrennial examinations.

Age-, sex-, and education-adjusted models were tested for each risk factor measured at each exam and within three adult age groups: early adults (ages 35 to 50, median 41), middle adults (ages 51 to 60, median 54), and late adults (ages 61 to 70, median 63.5).

A total of 271 participants (167 women, 104 men) diagnosed with Alzheimer’s dementia were included in the analysis as cases. Of these, 225 people were without stroke, 24 people had Alzheimer’s and stroke, and 24 people had mixed Alzheimer’s and vascular dementia. People with a diagnosis of non-Alzheimer’s dementia were excluded. Controls included 4,867 cognitively normal participants.

Mean follow-up periods for people in the early, middle, and late age groups were 35.2 years, 25.8 years, and 18.5 years, respectively. As participants grew older, they tended to have higher triglyceride and glucose levels, higher systolic and diastolic blood pressure, and lower HDL cholesterol levels. They also were more likely to be treated for diabetes, hypertension, and dyslipidemia.

Incident Alzheimer’s dementia was negatively associated with HDL cholesterol for every 15 mg/dL increase in early adulthood (HR 0.85, 95% CI 0.72-0.99, P=0.041) and in middle adulthood (HR 0.82, 95% CI 0.70-0.96, P=0.014). This association remained significant with a similar effect size in the middle adulthood group when adjusted for dyslipidemia treatment (P=0.022).

Analyses also showed:

• Triglyceride levels were associated with Alzheimer’s dementia only in the early adulthood group, before (HR 1.33, 95% CI 1.02-1.57, P=0.0013) and after (HR 1.30, 95% CI 1.10-1.54, P=0.0018) adjusting for dyslipidemia treatment
• Blood glucose in middle adulthood was associated with Alzheimer’s dementia per 15 mg/dL increase, before (HR 1.15, 95% CI 1.06-1.23, P=0.00029) and after (HR 1.18, 95% CI 1.08-1.29, P=0.00036) adjusting for diabetes treatment
• Diastolic blood pressure in late adulthood was associated with Alzheimer’s dementia per 10 mm increase, before (HR 1.14, 95% CI 1.01-1.29, P=0.041) and after (HR 1.14, 95% CI 1.00-1.29, P=0.044) adjusting for treatment
• Other vascular risk factors, including low-density lipoprotein (LDL) cholesterol, total cholesterol, BMI, smoking, and systolic blood pressure, were not associated with Alzheimer’s dementia in any stage of adulthood (P>0.05)

Future development of Alzheimer’s dementia was progressively higher and likely to occur earlier among people who had blood glucose in pre-diabetic (100 to 126 mg/dL) and diabetic (>126 mg/dL) ranges in early adulthood and middle adulthood.

“Intervention targeting cholesterol and glucose management starting in early adulthood can help maximize cognitive health in later life,” Farrer suggested.

That idea is supported by previous studies of Framingham Offspring participants showing that elevated coronary heart disease risk and metabolic syndrome were associated with lower cognitive performance at age 55, Zhang and co-authors noted.

“However, our results do not distinguish whether the influences of these risk factors on the development of Alzheimer’s disease may be particularly damaging during early adulthood and midlife or reflect longer accumulated risk exposure,” they wrote.

The study had several limitations, the researchers acknowledged. All participants were white, and some early measurements of lipids and glucose were not under fasting conditions. In addition, the findings were based on analyses of one-time measurements.