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Multicenter Study
. 2012 Aug;33(8):1599-608.
doi: 10.1016/j.neurobiolaging.2011.05.005. Epub 2011 Jun 17.

Body mass index is associated with biological CSF markers of core brain pathology of Alzheimer's disease

Michael Ewers  1 , Susanne Schmitz, Oskar Hansson, Cathal Walsh, Annette Fitzpatrick, David Bennett, Lennart Minthon, John Q Trojanowski, Leslie M Shaw, Yetunde O Faluyi, Bruno Vellas, Bruno Dubois, Kaj Blennow, Katharina Buerger, Stefan J Teipel, Michael Weiner, Harald Hampel; Alzheimer's Disease Neuroimaging Initiative
Collaborators, Affiliations
Multicenter Study

Body mass index is associated with biological CSF markers of core brain pathology of Alzheimer's disease

Michael Ewers et al. Neurobiol Aging. 2012 Aug.

Abstract

Weight changes are common in aging and Alzheimer's disease (AD) and postmortem findings suggest a relation between lower body mass index (BMI) and increased AD brain pathology. In the current multicenter study, we tested whether lower BMI is associated with higher core AD brain pathology as assessed by cerebrospinal fluid (CSF)-based biological markers of AD in 751 living subjects: 308 patients with AD, 296 subjects with amnestic mild cognitive impairment (MCI), and 147 elderly healthy controls (HC). Based upon a priori cutoff values on CSF concentration of total tau and beta-amyloid (Aβ(1-42)), subjects were binarized into a group with abnormal CSF biomarker signature (CSF+) and those without (CSF-). Results showed that BMI was significantly lower in the CSF+ when compared with the CSF- group (F = 27.7, df = 746, p < 0.001). There was no interaction between CSF signature and diagnosis or apolipoprotein E (ApoE) genotype. In conclusion, lower BMI is indicative of AD pathology as assessed with CSF-based biomarkers in demented and nondemented elderly subjects.

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Conflict of interest statement

Conflict of interest: Dr. Weiner has been on advisory boards for Lilly, Araclon and Institut Catala de Neurociencies Aplicades, Gulf War Veterans Illnesses Advisory Committee, VACO, Biogen Idec, Elan/Wyeth Alzheimer’s Immunotherapy Program North American Advisory Board, Novartis Misfolded Protein Scientific Advisory Board Meeting, Banner Alzheimer’s Institute Alzheimer’s Prevention Initiative Advisory Board Meeting, and the Research Advisory Committee on Gulf War Veterans’ Illnesses. He has been a consultant for Elan/Wyeth, Novartis, Forest, Ipsen, Daiichi Sankyo, Inc., Astra Zeneca, Araclon, Medivation/Pfizer, TauRx Therapeutics LTD, Bayer Healthcare, Biogen Idec, Exonhit Therapeutics, SA, Servier, and Synarc. He serves on the Alzheimer’s & Dementia Editorial Board. Dr. Weiner has received research support from Merck, Avid, the NIH, the DOD, and the VA, and holds stock options with Synarc and Elan. All other authors report no conflict of interest.

Figures

Figure 1
Figure 1
The box plot of the difference in BMI (log transformed) between CSF+ and CSF− signatures as a function of the different diagnostic groups as well as for the total sample is displayed. Subjects with a CSF+ had on average a smaller BMI than subjects with a CSF− signature across the different diagnostic groups.
Figure 2
Figure 2
The istribution of Bayesian estimate of probability distribution the regression coefficient of the difference between CSF+ and CSF− in BMI (log) based upon increasing amount of data is shown. The estimate of the regression coefficient is improved at different stages of successive entereing of data, starting with no data (empty circles), data from the ADNI study (black), Malmoe (red), and finally the combination of all 3 data sets (yellow). It becomes apparent that the mean difference between CSF signatures becomes more and more settled around the value of −0.06 (see results) and the distribution variance is decreased as the model “learns”, i.e. is successively informed by more data.
Figure 3
Figure 3
The scatter plots show BMI as a function of the standardized CSF concentration of total tau (A), p-tau181 (B), or Aβ1-42 (C). The data points are labelled according to diagnostic group. The regression line and associated 95% CI (curved lines) are displayed. The CSF concentration normalized to a standard normal distribution with a mean of 0 and SD of 1 is displayed for each CSF biomarker.
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Comment in

References

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