Plasma homocysteine is directly correlated with white matter hyperintensity and lateral ventricular volume, and inversely correlated with regional brain volumes in folic acid fortified, cognitively intact older adults

Abstract

Folic acid (FA) fortification has reduced the prevalence of hyperhomocysteinemia (HHcy) in the United States, but plasma homocysteine (Hcy) remains a modifiable risk factor for cognitive impairment and dementia. We investigated associations between white matter hyperintensity (WMH) and regional brain volumes, determined by structural MRI scans, and Hcy in cognitively intact, community dwelling older adults exposed to FA fortification (N=191, age 72±6y, Mini Mental State Score >;25). Mean Hcy was 8.6±3.7 μmol/L and 8.3% had HHcy (>;13 μmol/L). Mean RBC folate was 544±150 ng/ml and none was folate deficient (<160 ng/ml). Determinants of Hcy were age, education, vitamin B12, and creatinine. Folate was not correlated with Hcy. When controlling for age, gender, education, intracranial volume, folate, B12, and creatinine, Hcy was directly correlated with WMH (p=0.03) and lateral ventricular volume (p≤0.02), and inversely correlated with hippocampus (p≤0.08), amygdala (p≤0.01), basal ganglia (p≤0.06), and medial temporal lobe (p≤0.04) volumes. These results indicate that in folate replete, cognitively intact older adults, HCY is associated with WMH and structural deficits in and around the medial temporal lobe. It remains to be determined if Hcy predicts loss of volume in these brain regions and associated cognitive functions over time. NIH AG023501, AG032289; Hillblom Foundation; Private Foundation