Significance testing for high-dimensional generalized linear models (GLMs) has been increasingly needed in various applications, however, existing methods are mainly based on a sum of squares of the score vector and only powerful under certain alternative hypotheses. In practice, depending on whether the true association pattern under an alternative hypothesis is sparse or dense or between, the existing tests may or may not be powerful. In this paper, we propose an adaptive test on a high-dimensional parameter of a GLM (in the presence of a low-dimensional nuisance parameter), which can maintain high power across a wide range of scenarios. To evaluate its p-value, its asymptotic null distribution is derived. We conduct simulations to demonstrate the superior performance of the proposed test. In addition, we apply it and other existing tests to an Alzheimer's Disease Neuroimaging Initiative (ADNI) * Correspondence: wuxx0845@umn.edu (C.W.), weip@biostat.umn.edu (W.P.) † Data used in preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: