Late-life Obesity Is A Protective Factor For Prodromal Alzheimer’s Disease:A Longitudinal Study

Background: Higher body mass index(BMI)and Alzheimer’s disease(AD)are increasingly important public health issues and the role of higher BMI on AD may change during life.Higher BMI in late-life has recently been considered as a possible protective factor for AD,which yet remains conflicting.Objective: We detected the impact of late-life BMI on Alzheimer’s disease,particularly in the early disease stages.Methods: We evaluated the cross-sectional and longitudinal associations of BMI categories with CSF biomarkers,brain structure,brain Aβload,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.Furthermore,we analysed their association in normal cognition(NC)and mild cognitive impairment(MCI)subgroup.Results: At baseline,higher late-life BMI categories were associated with higher levels of CSF β-amyloid42(Aβ42,β= 0.335,p=0.037),lower levels of CSF total-tau(t-tau,β=-0.023,p=0.026)and CSF t-tau/Aβ42(β=-0.093,p=0.008),as well as larger volumes of hippocampus(β= 129.579,p<0.0001),entorhinal cortex(β=74.083,p=0.009)and middle temporal lobe(β=204.24,p=0.040).But no association was found with CSF phosphorylated-tau(p-tau,p=0.550)or CSF p-tau/Aβ42(p = 0.180).Higher baseline BMI categories was associated with lower load of Aβ in the right hippocampus(β =-0.010,p=0.030).Furthermore,longitudinal studies showed that higher BMI individuals experienced a slower decline in cognitive function(ADAS-Cog11,β=-0.351,p=7.52e-05;ADAS-Cog13,β=-0.491,p =3.47e-06;MMSE,β= 1.56e-01,p = 0.001;ADNI-EF,β= 3.15e-02,p = 2.87e-05;ADNI-MEM,β= 2.60e-02,p = 4.07e-05).Finally,Kaplan–Meier survival analysis revealed that late-life BMI was inversely associated with AD risk(p = 0.009).However,further adjustment for confounding variables made little difference to this inverse association between BMI and AD risk(p=0.160).Conclusions: Our results suggest that higher BMI in late life plays a protective role against AD,which may be driven by AD-related biomarkers.