Relative contributions of biomarkers in Alzheimer’s disease

PurposeTo assess relationships between biomarkers for Alzheimer’s disease (AD) and their potential contributions to AD.MethodsBiomarkers 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.ResultsAt 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.ConclusionsBrain glucose metabolism and hippocampal volume represent relevant biological markers in subjects at risk for AD.