Midlife lipid and glucose levels are associated with Alzheimer's disease

Abstract

Introduction: It is unknown whether vascular and metabolic diseases assessed in early adulthood are associated with Alzheimer's disease (AD) later in life.

Methods: Association of AD with lipid fractions, glucose, blood pressure, body mass index (BMI), and smoking obtained prospectively from 4932 Framingham Heart Study (FHS) participants across nine quadrennial examinations was evaluated using Cox proportional hazard and Kaplan-Meier models. Age-, sex-, and education-adjusted models were tested for each factor measured at each exam and within three adult age groups (early = 35-50, middle = 51-60, and late = 61-70).

Results: A 15 mg/dL increase in high density lipoprotein (HDL) cholesterol was associated with decreased AD risk during early (15.4%, P = 0.041) and middle (17.9%, P = 0.014) adulthood. A 15 mg/dL increase in glucose measured during middle adulthood was associated with 14.5% increased AD risk (P = 0.00029). These findings remained significant after adjusting for treatment.

Discussion: Our findings suggest that careful management of cholesterol and glucose beginning in early adulthood can lower AD risk.

Keywords: Alzheimer's disease; Midlife; cardiovascular risk factors; glucose; high-density lipoprotein cholesterol; lipids.

FIGURE 1

Study design

FIGURE 2

Cumulative probability of Alzheimer's disease (AD)–free survival among individuals stratified into three (left panel) or two (right panel) clinically defined cutoffs for blood glucose (BG) concentration who were followed starting in (A) early adulthood (ages 35‐50 years) (B) middle adulthood (ages 51‐60 years), and (C) late adulthood (ages 61‐70 years). The number of years of follow‐up and number of surviving individuals in each BG level group are shown below the x‐axis. Lighter shades of color indicate standard deviation of point estimates