Body Mass Index and Polygenic Risk for Alzheimer’s Disease Predict Conversion to Alzheimer’s Disease

Abstract

Body mass index (BMI) is a risk factor for Alzheimer’s disease (AD) although the relationship is complex. Obesity in midlife is associated with increased risk for AD, whereas evidence supports both higher and lower BMI increasing risk for AD in late life. This study examined the influence of individual differences in genetic risk for AD to further clarify the relationship between late-life BMI and conversion to AD. Participants included 52 individuals diagnosed as having mild cognitive impairment (MCI) at baseline who converted to AD within 24 months and 52 matched MCI participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort. BMI was measured at baseline. Genetic risk for AD was assessed via genome-wide polygenic risk scores. Conditional logistic regression models were run to determine if BMI and polygenic risk predicted conversion to AD. Results showed an interaction between BMI and genetic risk, such that individuals with lower BMI and higher polygenic risk were more likely to convert to AD relative to individuals with higher BMI. These results remained significant after adjusting for cerebrospinal fluid biomarkers of AD. Exploratory sex-stratified analyses revealed this relationship only remained significant in males. These results show that higher genetic risk in the context of lower BMI predicts conversion to AD in the next 24 months, particularly among males. These findings suggest that genetic risk for AD in the context of lower BMI may serve as a prodromal risk factor for future conversion to AD.

Total and regional fat‐to‐muscle mass ratio and risks of incident all‐cause dementia, Alzheimer's disease, and vascular dementia

“…Sex hormone and inflammation seemed to be involved. For example, among people genetically susceptible to AD, a stronger risk of AD was observed in men with lower BMI compared with women, possibly due to the identification of testosterone as a risk factor for AD in the preclinical phase and its association with adipogenesis inhibition in men 22 . In addition, findings point to that obesity in women leads to a greater increase in inflammatory responses than in men, and there is a greater association between inflammation and AD risk in women 23 .…”

Exact Statistical Distribution and Correlation of Human Height and Weight: Analysis and Experimental Confirmation

“…For further confirmation, consider again the information in Table 1. In the first section of the table, empirical values of the mean, standard deviation, skewness, and kurtosis of ANSUR heights H and weights W are compared with corresponding values predicted by lognormal expressions (7) to (10), based on the parameters in the second section of the table, derived from the variates of lnH and lnW. Agreement of experiment and theory is seen to be within 1 standard error (se) in most cases.…”

“…Although more refined studies have revealed that anthropometric data can show deviations from normality, attempts to find relationships between human height and weight remained uncertain, controversial and based on approximate or indirect methods such as data fitting [5], mechanical modeling [6], and gene identification [7]. Height and weight are of particular importance since they directly relate to the body mass index (BMI) [8], which is a measure of obesity and a risk factor for metabolic disease [9] and Alzheimer's Disease [10]. A previous paper by Silverman and Lipscombe [11], to be referred to as Part I, determined the mathematically exact statistical distribution of BMI.…”

Can T1-Weighted Magnetic Resonance Imaging Significantly Improve Mini-Mental State Examination-Based Distinguishing Between Mild Cognitive Impairment and Early-Stage Alzheimer’s Disease?

“…People suffering from MCI have a high rate of progression to dementia over a relatively short period, but not everyone will develop AD [ 3 ]. Within a 3-year follow-up period, about 35% of patients with MCI status progress to AD or dementia [ 4 ]. A yearly conversion rate equals 5% –10% [ 4 ].…”