Serum Ethanolamine Plasmalogen and Urine Myo-Inositol as Cognitive Decline Markers.

Abstract

Recent studies have suggested that metabolic disorders, particularly type 2 diabetes mellitus (T2DM), and dementia, including Alzheimer's disease (AD), were linked at the clinical and molecular levels. Brain insulin deficiency and resistance may be key events in AD pathology mechanistically linking AD to T2DM. Ethanolamine plasmalogens (PlsEtns) are abundant in the brain and play essential roles in neuronal function and myelin formation. As such, PlsEtn deficiency may be pathologically relevant in some neurodegenerative disorders such as AD. Decreased brain PlsEtn associated with dementia may reflect serum PlsEtn deficiency. We hypothesized that myo-inositol plays a role in myelin formation through its facilitation of PlsEtn biosynthesis. Excessive urinary myo-inositol (UMI) loss would likely result in PlsEtn deficiency potentially leading to demyelinating diseases such as dementia. Accordingly, measurement of both serum PlsEtn and baseline UMI excretion could improve the detection of cognitive impairment (CI) in a more specific and reliable manner. To verify our hypothesis, we conducted a clinical observational study of memory clinic outpatients (MCO) and cognitively normal elderly (NE) for nearly 4.5years. We demonstrated that serum PlsEtn concentration associated with UMI excretion was useful for predicting advancing dementia in patients with mild CI. Because hyperglycemia and associated insulin resistance might be a leading cause of increased baseline UMI excretion, serum PlsEtn quantitation would be useful in detecting CI among the elderly with hyperglycemia. Our findings suggest that myo-inositol is a novel candidate molecule linking T2DM to AD.