Late-life obesity is a protective factor for prodromal Alzheimer's disease: a longitudinal study - PubMed (original) (raw)

Late-life obesity is a protective factor for prodromal Alzheimer's disease: a longitudinal study

Zhen Sun et al. Aging (Albany NY). 2020.

Abstract

Higher body mass index (BMI) in late-life has recently been considered as a possible protective factor for Alzheimer's disease (AD), which yet remains conflicting. To test this hypothesis, we have evaluated the cross-sectional and longitudinal associations of BMI categories with CSF biomarkers, brain β-amyloid (Aβ) load, brain structure, and cognition and have assessed the effect of late-life BMI on AD risk in a large sample (n = 1,212) of non-demented elderly from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. At baseline, higher late-life BMI categories were associated with higher levels of CSF Aβ42 (p=0.037), lower levels of CSF total-tau (t-tau, p=0.026) and CSF t-tau/Aβ42 (p=0.008), lower load of Aβ in the right hippocampus (p=0.030), as well as larger volumes of hippocampus (p<0.0001), entorhinal cortex (p=0.009) and middle temporal lobe (p=0.040). But no association was found with CSF phosphorylated-tau (p-tau) or CSF p-tau/Aβ42. Longitudinal studies showed that higher BMI individuals experienced a slower decline in cognitive function. In addition, Kaplan-Meier survival analysis revealed that higher late-life BMI had a reduced risk of progression to AD over time (p = 0.009). Higher BMI in late-life decreased the risk of AD, and this process may be driven by AD-related biomarkers.

Keywords: Alzheimer’s disease; biomarker; body mass index; brain volume; cognition.

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Conflict of interest statement

CONFLICTS OF INTEREST: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1

Figure 1

The cross-sectional associations of BMI categories with CSF biomarker levels in the whole population and the subgroups stratified by cognitive diagnosis. (A) Higher late-life BMI categories were associated with a higher level of CSF Aβ42 and lower levels of CSF t-tau (B) and CSF t-tau/Aβ42 (C). All analyses were adjusted for age, sex, education, cognitive diagnosis, ApoE ε4 status, CSF volume and prevalent comorbidities (i.e., hypertension, hyperlipemia, DM2, depression and CVD). Abbreviations: BMI = body mass index; MCI = mild cognitive impairment; NC = normal cognition; Aβ42 =β-amyloid42; t-tau = total-tau.

Figure 2

Figure 2

The cross-sectional associations of BMI categories with brain volumes in the whole population. Higher BMI categories were associated with larger volumes of hippocampus (A), entorhinal cortex (B) and middle temporal lobe (C). All analyses were adjusted for adjusting for age, sex, education, cognitive diagnosis, ApoE ε4 status, prevalent comorbidities (i.e., hypertension, hyperlipemia, DM2, depression and CVD) and total intracranial volumes. Abbreviations: BMI = body mass index;CVD = Cardiovascular Diseases;DM2 = Diabetes Mellitus Type 2.

Figure 3

Figure 3

The longitudinal associations of BMI categories with cognitive performance in the entire sample. Higher BMI categories were associated with slower rates of cognitive decline on ADAS-Cog11 (A), ADAS-Cog13 (B), MMSE (C), ADNI-EF (D) and ADNI-MEM (E) over the following ten years. All analyses were adjusted for age, sex, education, cognitive diagnosis, ApoE ε4 status, as well as prevalent comorbidities (i.e., hypertension, hyperlipemia, DM2, depression and CVD). Abbreviations: BMI = body mass index; ADAS-Cog = Alzheimer Disease Assessment Scale-cognitive subscale; MMSE = Mini-Mental State Examination.

Figure 4

Figure 4

Kaplan-Meier curves comparing survival free from progression to AD according to baseline body mass index (BMI) categories. Individuals with higher BMI categories had a lower risk of progression to AD over the following six years. Abbreviations: BMI = body mass index.

Figure 5

Figure 5

Flowchart showing the samples used in this work and the subsets utilized for analyses. Abbreviations: AD = Alzheimer's disease; CSF =Cerebrospinal Fluid.

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