Recently, we discovered that single nucleotide polymorphisms (SNPs) ARNTL rs900147 and PER1 rs2253820 were significantly associated with Parkinson's disease (PD). Both ARNTL and PER1 play essential roles in regulating the circadian rhythm, and disruption of the circadian system leads to an increased likelihood of developing both Alzheimer's disease (AD) and PD. Therefore, it is reasonable to speculate that these SNPs may also be of relevance to AD as well as to amnestic mild cognitive impairment (aMCI), the prodromal (predementia) phase of AD. To test this hypothesis, we genotyped rs900147 and rs2253820 in 136 AD patients, 151 aMCI patients, and 257 healthy controls from a Chinese population using direct sequencing. A significant difference was observed for rs900147 between AD and control subjects regarding the genotypic distribution (p = 0.001) and allele frequency (p = 0.001), as well as between aMCI and control subjects regarding the genotypic distribution (p = 0.046) and allele frequency (p = 0.020). Carriers of the G allele were shown to be significantly more prone to developing AD and aMCI than other carriers. No significant difference was observed for rs2253820. This study revealed that variations in ARNTL are associated with AD/aMCI, and may represent genetic risk factors for AD/aMCI.