Homocysteine, vitamin B6, and vascular disease in AD patients

Background: Cerebrovascular disease is a cause of dementia and is associated with elevated plasma levels of homocysteine, Patients with AD tend to have unexplained elevations of homocysteine concentrations vs healthy control subjects. Vitamin B-6 status, a potential determinant of plasma homocysteine, has not been characterized in patients with AD. Objective: To investigate plasma homocysteine, vitamin B-6 status, and the occurrence of vascular disease in patients with AD. Methods: Forty-three patients with AD and 37 control subjects without AD were studied for homocysteine, B vitamin status (folate, vitamin B-12, pyridoxal-5'-phosphate [PLP]), kidney function (creatinine), and thyroid function (thyroid-stimulating hormone, thyroxin). In addition, the presence of vascular disease was assessed by reviewing both medical histories and brain imaging data provided by CT and MRI. Results: The OR for elevated plasma homocysteine (>12 mumol/L) was only 2.2 (not significant) for subjects with AD. In contrast, the OR was 10.0 (p = 0.03) for subjects with vascular disease (n = 26). The OR for low plasma PLP (<25 nmol/L) was 12.3 (p = 0.01) for patients with AD. No significant relationship was observed between vascular disease and PLP level or between plasma homocysteine and PLP concentrations. Conclusions: Elevated plasma homocysteine in patients with AD appears related to vascular disease and not AD pathology. In addition, low vitamin B-6 status is prevalent in patients with AD. It remains to be determined if elevated plasma homocysteine or low vitamin B-6 status directly influences AD pathogenesis or progression.