Changes in alkaline phosphate and calcium levels during early mild cognitive impairment, indicating a role for bone in the progression of Alzheimer’s disease

Abstract

AbstractBackgroundOver 50 million people worldwide have dementia, one of its most common form being Alzheimer’s disease. It’s one of the top ten leading causes of death attributing to the extraneuronal effects in the bone, skeletal muscle, liver, kidney, and heart. Falls and fractures are one of the predominant causes of mortality in AD patients, indicating the cross talk between the bone and brain during AD. Women with lower femoral BMD were two times more risk‐prone to develop AD than women with higher BMD and this was found to be independent of other risk factors of AD. In this study, we are investigating the changes in the bone markers during early stages of the AD.MethodThe Alzheimer’s Disease Neuroimaging Initiative(ADNI) is a multisite, longitudinal study of normal cognitive aging, early Mild cognitive impairment(EMCI), late MCI and AD individuals, wherein specific recruitment methods are used to recruit participants. We analyzed data from the ADNI‐1, ADNIGO and ADNI‐1 focusing on the relationships between the severity of dementia (mini‐mental state scores), the clinical musculoskeletal findings, and the laboratory data from these participants, which included fluid biomarkers. A total of 1765 patients were included, 57% male and 43% female.ResultWe observed in females that there was robust decrease in the alkaline phosphate levels in EMCI group compared to normal cognitive group, whereas a significant increase in alkaline phosphate levels between EMCI and AD groups. The higher alkaline phosphate levels at EMCI indicates the activity of bone cells and thus bone remodeling. In males, there was a significant reduction in the alkaline phosphate levels during EMCI when compared to cognitive normal groups; however, alkaline phosphate levels were significantly increased both in LMCI and AD groups when compared to EMCI group. Also, in males, there was significant decrease in the calcium levels from cognitive normal group to EMCI group, which was further significantly reduced in the AD groups. However, there was no change in calcium across the groups in the females.ConclusionDetecting changes in the bone biomarkers early on, will help in better management of AD, thereby improving the quality of life in these patients.