Abstract

ABSTRACT Background Despite some reports of cardiometabolic disorders associated with the risk of Alzheimer's disease (AD), limited studies have been conducted to examine the association between excessive sugar intake (a risk factor for cardiometabolic disorders) and AD risk. Aim The purpose of our study was to evaluate if excessive sugar intake has a significant long-term effect on the risk of AD. Methods A population sample of 37,689 participants, who enrolled in the United States (US) Women's Health Initiative – Dietary Modification Trial (WHI-DM) in 1993–2005 and its extended observational follow-up study through 1 March 2019, were analyzed. Dietary sugar intake was measured using food frequency questionnaires. AD was classified by reports using a standard questionnaire. A dietary pattern that explained the maxima variations in sugar intake was constructed using reduced rank regression (RRR) technique. Associations of RRR dietary pattern scores and sugar intake (g/day) by quartiles (Q1 through Q4) with AD risk were examined using Cox proportional hazards regression analysis with adjusting for key covariates. Results During a mean follow-up of 18.7 years, 4586 participants reported having incident AD. The total incidence rate (95% confidence interval [CI]) of AD was 6.5 (6.3–6.7) per 1000 person-years (PYs). The incidence rates (95% CI) of AD by total sugar intake were 6.2 (5.8–6.6), 6.4 (6.0–6.8), 6.6 (6.3–7.0), and 6.9 (6.5–7.3) per 1000 PYs among those in quartiles (Q) 1 to Q4 (toward higher sugar consumption) of total sugar intake, respectively (test for trend of AD incident rates, p < 0.001). Individuals in Q4 of total sugar intake had a 1.19 higher risk of incident AD than those in Q1 (hazard ratio [HR] = 1.19, 95% CI: 1.05–1.34, p = 0.01). An estimated increase of 10 g/day in total sugar intake (about 2.4 teaspoons) was associated with an increased AD risk by 1.3–1.4%. Of six subtypes of sugar intake, lactose was significantly associated with AD risk. Conclusions Our study indicates that excessive total sugar intake was significantly associated with AD risk in women. Of six subtypes of sugar intake, lactose had a stronger impact on AD risk.

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