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

Abstract

The associations between obesity and Alzheimer's disease (AD) at different ages have been debated. Recent evidence implied the protective effects of metabolically healthy obesity on AD. We hypothesized that obesity and lipids could mitigate the detrimental impacts of AD pathological changes among metabolically healthy individuals in late life. In this study, a total of 604 metabolically healthy participants with normal cognition were included from the Chinese Alzheimer's Biomarker and LifestylE (CABLE) database. Multiple linear regression models were used to test the associations of body mass index (BMI) or lipids with cerebrospinal fluid (CSF) biomarkers after adjustment for age, gender, education, and Apolipoprotein E-ɛ4 (APOE-ɛ4). The results showed the lower CSF levels of total tau protein (t-tau: p = .0048) and phosphorylated tau protein (p-tau: p = .0035) in obese participants than in non-obese participants, even after correcting for covariates. Moreover in late life, higher BMI was associated with decreased CSF t-tau (β: −0.15, p = .0145) and p-tau (β: −0.17, p = .0052). As for lipids, higher levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were associated with decreased CSF t-tau (TC: β: −0.16, p = .0115; LDL-C: β: −0.16, p = .0082) and p-tau (TC: β: −0.15, p = .0177; LDL-C: β: −0.14, p = .0225) in obese participants. Furthermore, these associations were only significant in participants with late-life obesity and APOE-ɛ4 non-carriers. Overall, in a cognitively normal population, we found metabolically healthy obesity and lipids in late life might be protective factors for neurodegenerative changes.

Blood-Based Biomarkers for Alzheimer’s Disease Diagnosis and Progression: An Overview

“…However, reproducibility issues remain, particularly concerning the criteria used for patient distribution into subgroups. For example, evidence from a cross-sectional study conducted on 1889 Chinese participants reported an inverse U-shaped association between total cholesterol levels and cognitive score only in the subgroup of patients characterized by normal levels of homocysteine [ 325 ], while Huang et al could reach statistical significance only in late-life obese APOE-ε 4 non-carriers [ 326 ]. Furthermore, similar to the U-shaped relationship observed for total cholesterol, higher plasma HDL levels have been found in AD patients versus controls in two prospective population-based investigations [ 327 ], while very low circulating HDL content was reported to be associated with cognitive decline [ 328 ].…”

Association between Life’s Simple 7 and cerebrospinal fluid biomarkers of Alzheimer’s disease pathology in cognitively intact adults: the CABLE study

“…Besides, the interaction between age and behavior metrics was found. In the mid-age, we found that both biological metrics and behavior metrics were relevant to CSF biomarkers, while in the late age, there was only biological metrics revealed significant association, which might be due to the complex effects of BMI on dementia attenuating the significance of behavior metrics in late life [ 38 , 39 ]. Also, the association of biological metrics was only found in males, which could be derived from the different distribution of LS7 scores between the genders (Additional file 1 : Fig.…”

Association between air pollution and CSF sTREM2 in cognitively normal older adults: The CABLE study

“…Comorbidities information was determined according to the diagnoses or medical history recorded in the electronic medical record (EMR) systems, including the history of stroke, diabetes, coronary heart disease, and hypertension. In subgroups analyses, a cut‐off of 65 years was set to define the mid‐ or late‐life stage, 27 and individuals with a BMI≥25 kg/m 2 were classified as obese 28…”

“…The epidemiological characteristics of included participants in CABLE were summarized in Table 1. A total of 1,131 normal cognitive individuals (CM-MMSE score median, 28; IQR, [27][28][29][30] were involved in the study, with a median educational year of 9 (IQR, 9-12). In brief, the mean age of the study population was 62.47 (SD, 10.34) years, the percentage of females was 41.1%, and the proportion of APOE-e4 carriers was 15.2%.…”