Blood D-Amino Acid Oxidase Levels Increased With Cognitive Decline Among People With Mild Cognitive Impairment: A Two-Year Prospective Study

Background: Dysregulation of N-methyl-D-aspartate receptor (NMDAR) neurotransmission has been reported to be implicated in the pathogenesis of Alzheimer's disease (AD). D-amino acid oxidase (DAO), responsible for degradation of NMDAR-related D-amino acids such as D-serine, regulates NMDAR function. A cross-section study found that serum DAO levels were positively related with the severity of cognitive aging among elderly individuals. This 2-year prospective study aimed to explore the role of DAO levels in predicting the outcome of patients with very early-phase AD, such as mild cognitive impairment (MCI).

Methods: Fifty-one patients with MCI and 21 healthy individuals were recruited. Serum DAO levels and cognitive function, measured by the AD assessment scale-cognitive subscale and the Mini-Mental Status Examination, were monitored every 6 months. We employed multiple regressions to examine the role of DAO concentration in cognitive decline in the 2-year period.

Results: From baseline to endpoint (24 months), serum DAO levels increased significantly, and cognitive ability declined according to both cognitive tests in the MCI patients. Among the healthy individuals, DAO concentrations also increased and Mini-Mental Status Examination scores declined; however, AD assessment scale-cognitive subscale scores did not significantly change. Further, DAO levels at both months 12 and 18 were predictive of cognitive impairment at month 24 among the MCI patients.

Conclusions: To our knowledge, this is the first study to demonstrate that blood DAO levels increased with cognitive deterioration among the MCI patients in a prospective manner. If replicated by future studies, blood DAO concentration may be regarded as a biomarker for monitoring cognitive change in the patients with MCI.