Overweight in midlife and risk of dementia: a 40-year follow-up study

Abstract

Objective: This study examines whether overweight in midlife increases dementia risk later in life. Methods: In 1963 body mass index was assessed in 1152 participants of The Swedish Twin Registry, at the age of 45-65 years. These participants were later screened for dementia in a prospective study with up to 40 years follow-up. A total of 312 participants were diagnosed with dementia. Results: Logistic regression analyses adjusted for demographic factors, smoking and alcohol habits, indicated that men and women categorized as overweight in their midlife had an elevated risk of dementia (OR ¼ 1.59; 95% CI: 1.21-2.07, P ¼ 0.002), Alzheimer's disease (OR ¼ 1.71; 95% CI: 1.24-2.35, P ¼ 0.003), and vascular dementia (OR ¼ 1.55; 95% CI: 0.98-2.47, P ¼ 0.059). Further adjustments for diabetes and vascular diseases did not substantially affect the associations, except for vascular dementia (OR ¼ 1.36; 95% CI: 0.82-2.56, P ¼ 0.116), reflecting the significance of diabetes and vascular diseases in the etiology of vascular dementia. There was no significant interaction between overweight and APOE e4 status, indicating that having both risk factors does not have a multiplicative effect with regard to dementia risk. Conclusions: This study gives further support to the notion that overweight in midlife increases later risk of dementia. The risk is increased for both Alzheimer's disease and vascular dementia, and follows the same pattern for men and women.

Midlife overweight and obesity increase late-life dementia risk

“…A growing body of evidence suggests that a high level of adiposity is associated with cognitive decline and dementia 10,26,27 ; however, the relation between BMI and dementia among people aged over 65 is controversial. [28][29][30] Several population-based studies have reported an effect of obesity at middle age on dementia risk.…”

“…2 In the last decade, many population-based longitudinal studies have evaluated the relationship between adiposity and dementia. Several reports have shown that midlife obesity increases the risk of dementia in late life [3][4][5][6][7][8][9][10] ; however, the effect of midlife overweight on dementia is controversial. 3,5,7,9 Currently, the prevalence of overweight and obesity is over 50% among adults in the United States and Europe.…”

Gene-Environment Interactions Controlling Energy and Glucose Homeostasis and the Developmental Origins of Obesity

“…However, as with other diseases, the relationship between BMI and T2DM risk also varies by ethnicity (314,499). Other diseases associated with obesity include various types of cancer (70,112,201,433), ischemic stroke (358,501,579), heart failure (245), dementia (202), venous thrombosis (7), gallstones (489), gastroesophageal reflux disease (386), renal disease (145), sleep apnea (570), and osteoarthritis (83). Particularly pertinent to this review, maternal obesity is associated with gestational complications and adverse fetal and neonatal health outcomes (348,513).…”

Inflammation, Defective Insulin Signaling, and Mitochondrial Dysfunction as Common Molecular Denominators Connecting Type 2 Diabetes to Alzheimer Disease

“…A recent study showed that the hypothalamus of obese humans and of experimental models of obesity presents signs of inflammation and dysfunction that precede the installation of increased adiposity and T2D (15). Obesity, often associated with consumption of diets that are high in fat, has also been proposed to increase the risk of dementia and AD later in life (16)(17)(18). Epidemiologic studies further suggest that diets high in saturated fats during midlife are a risk factor for development of AD later in life (19,20).…”