Metabolically healthy obesity reduces the risk of Alzheimer’s disease in elders: a longitudinal study

Abstract

A subgroup of overweight/obese individuals, who had favorable metabolic profiles, was termed as metabolically healthy overweight/obese (MHO). Several studies suggested that MHO individuals were not at increased risk of cardiovascular disease and all-course mortality. However, whether MHO is associated with excess risk of Alzheimer’s disease (AD) in elders remains unclear. To explore the risk of AD among MHO phenotype and investigate whether MHO associates with neurodegenerative biomarkers of AD, we assessed body mass index-metabolic status phenotypes of 1199 longitudinal elders from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort using the Adult Treatment Panel-III (ATP- III) criteria. MHO subjects were at a significantly decreased risk for AD (adjusted HR=0.73, 95% CI: 0.54-0.97) compared with metabolically healthy normal weight (MHNW) subjects. In multivariable linear regression models, the cross-sectional associations of MHO with cerebrospinal fluid (CSF) biomarkers, brain Aβ load, and cortical structure were explored. MHO was positively correlated with CSF-Aβ (β=0.746, P=0.015), hippocampal volume (β=0.181, P=0.011), and whole brain volume (β=0.133, P=0.004). The MHO phenotype of the elder conferred a decreased risk of AD and its role may be driven by Aβ.

The risk of Alzheimer’s disease according to dynamic changes in metabolic health and obesity: a nationwide population-based cohort study

“…In this nationwide population-based cohort study, we showed that the risk of AD was significantly reduced among MHO individuals, which was in line with the results of previous studies [ 2 , 19 ]. Additionally, we analyzed the risk of AD according to phenotypic transitions observed during subsequent biannual examinations.…”

“…Recently, two cohort studies investigated the implications of obesity without metabolic unhealthiness on AD incidence [ 2 , 19 ]. A Korean study using a nationwide cohort reported that the MHO group was at the lowest risk of AD (HR 0.87; 95% CI, 0.86–0.88) relative to the MHNO group [ 19 ].…”

“…The estimated number of patients with dementia is projected to reach 106 million worldwide by 2050 [ 1 ]. Alzheimer’s disease (AD) is the most common type of dementia, with an incidence of 60% to 80% [ 2 ], but no preventive or disease-modifying therapies are currently available [ 1 ]. Hence, the detection of modifiable risk factors is of critical importance.…”

“…Several studies have reported that MHO people are neither at increased risk of cardiometabolic disease nor mortality compared with normal-weight controls [ 17 , 18 ]. The prognostic value of MHO, however, could be largely dependent on health outcomes; indeed, a few recent studies have reported that MHO individuals are at even lower risk of AD than previously thought [ 2 , 19 ].…”

Metabolically healthy obesity and lipids may be protective factors for pathological changes of alzheimer’s disease in cognitively normal adults

“…Neuroimaging Initiative (ADNI) database also got similar results and found that metabolically healthy obesity in late life was associated with mild pathological changes in CSF AD biomarkers as well as in the whole brain volume or hippocampal volume (Ma et al, 2019).…”