Ferguson, Keelin. Hyperhomocysteinemia as an early modifiable biomarker of age-related cognitive decline and risk of Alzheimer disease. Retrieved from https://doi.org/doi:10.7282/t3-6aaa-de09
DescriptionStatement of Problem: Studies have demonstrated associations between elevated plasma homocysteine and cognitive impairment, Alzheimer’s disease, and dementia. This study sought to explore the relationship between elevated plasma homocysteine, regional brain volumes, and cognitive function in older adults with no overt cognitive impairment and the potential of elevated homocysteine to serve as an early modifiable biomarker for age-related neurodegeneration and cognitive decline. Objective: We evaluated the relationship between plasma homocysteine, regional brain volumes, and cognitive function in older adults with no cognitive impairment (age 69-90 y; N=243, 129 women, 114 men).
Methods: Blood samples were collected to determine concentration of plasma total homocysteine, RBC folate, serum vitamin B12 and serum creatinine. Cognitive function tests included assessment of global cognitive function, processing speed, verbal memory, and executive function. Regional brain volume scans were conducted using MRI imaging analyzed by Freesurfer. Associations between plasma homocysteine, cognitive function and regional brain volumes were assessed using multiple regression analysis with control for age, sex, education, RBC folate, vitamin B12 and serum creatinine.
Results: Homocysteine was inversely correlated with 12 of 15 regional brain volumes (P<0.05) after adjusting for demographic and biochemical variables. Homocysteine was inversely correlated with 3 of the 12 cognitive function tests (P<0.05) after adjusting for demographic and biochemical variables. The three cognitive function tests that were significantly associated with homocysteine were tests of executive functions.
Conclusions: Elevated homocysteine can serve as an early modifiable risk factor for impaired cognitive function and neurodegeneration in healthy adults without overt clinical cognitive impairment. Further research is needed to confirm if lowering homocysteine with B vitamin supplements will slow the progression of neurodegeneration and cognitive decline in older adults.