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. 2012 Dec;22(12):868-75.
doi: 10.1016/j.annepidem.2012.09.004. Epub 2012 Oct 24.

Relative contributions of biomarkers in Alzheimer's disease

Thaddeus J Haight  1 , William J Jagust; Alzheimer’s Disease Neuroimaging Initiative
Affiliations

Relative contributions of biomarkers in Alzheimer's disease

Thaddeus J Haight et al. Ann Epidemiol. 2012 Dec.

Abstract

Purpose: To assess relationships between biomarkers for Alzheimer's disease (AD) and their potential contributions to AD.

Methods: Biomarkers and cognitive evaluations were assessed longitudinally in 179 patients with mild cognitive impairment, from the Alzheimer's Disease Neuroimaging Initiative from 2003 to 2006, and were used to examine, at any given time, the joint contributions of hippocampal volume, whole brain volume, and brain glucose metabolism on clinical AD progression, using the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog). Marginal structural models were applied, and an inverse-probability of treatment weight estimation was used to account for time-dependent confounding between study variables.

Results: At any given time, population-level differences (e.g., 1-standard deviation [SD] increase) in brain glucose metabolism (-1.036; 95% confidence interval [95% CI], -1.608, -0.464) and hippocampal volume (-1.537; 95% CI, -2.399, -0.674) independently reduced mean (ADAS-Cog), whereas a 1-SD increase in whole brain volume did not (0.372; 95% CI, -0.283, 1.027). The effects of brain glucose metabolism differed in subgroups defined by baseline covariates (e.g., age), but no subgroup effects were observed for hippocampal volume and brain volume.

Conclusions: Brain glucose metabolism and hippocampal volume represent relevant biological markers in subjects at risk for AD.

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Figures

FIGURE 1
FIGURE 1
Brain volume and hippocampal volume can directly affect ADAS-Cog as well as through reduction in brain glucose metabolism, as measured by FDG-PET. These measures are affected also by reduction in glucose metabolism which is the result of reduced neuronal/synaptic activity. Marginal structural models were applied and estimated to assess the independent effects of the different biomarkers with respect to ADAS-Cog. Hypothetical pathways by which different biomarkers for Alzheimer’s Disease (AD) affect cognitive function (ADAS-Cog), a marker of AD progression, at any given time t.
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