Vitamin B12 May Reduce the Rate of Brain Volume Loss in Older People without Dementia

Background

Vitamin B₁₂, folate and sulfur amino acids have been associated with an array of disorders, including cerebrovascular changes in elderly people. It is important to understand the potential impact of the trio on structural brain changes, considering that all three are modifiable factors. Thus, vitamin B₁₂, folate and sulfur amino acids provide a potential target to chalk out novel prevention strategies.

Objective

To examine the association of levels of vitamin B₁₂, red blood cell (RBC) folate, and sulfur amino acids with changes in brain tissue volumes and total white matter hyperintensity (WMH) over six years in older people without dementia.

Study Population

• Elderly people (age; at least 60 years) without dementia (n=501)
• Mean age of the study population was 70.9 years and 59.9% of them were women

Method

Study Design

• Population-based longitudinal study

Assessments

• A structural magnetic resonance imaging (MRI) was performed at baseline and every 3 years thereafter for the older cohort (≥78 years at baseline) and every 6 years hereafter for the whole cohort.
• A total of 299 participants underwent repeated structural brain magnetic resonance imaging scans at follow-up.
• Total gray matter volume (GMV), white matter volume (WMV), and total white matter hyperintensity were measured using fluid-attenuated inversion recovery. Total brain tissue (TBT) volume was obtained by adding GMV and WMV. Total intracranial volume was then calculated by adding the volumes of TBT and cerebrospinal fluid (CSF).
• Biochemical analyses were performed to measure the levels of vitamin B₁₂, holotranscobalamin (holoTC), and sulfur amino acids (total homocysteine, methionine, cystathionine, cysteine, and glutathione).
• The association of the levels of vitamin B₁₂, holoTC, RBC folate, and sulfur amino acids with brain volumes and WMH over 6 years was performed using linear mixed models.

Results

Association of Concentrations of Vitamin B12, Folate, and Sulfur Amino Acids with Brain Atrophy

Vitamin B₁₂ and HoloTC

• No cross-sectional association was observed between values for vitamin B₁₂, holoTC, and brain volumes.
• In the longitudinal analysis over 6 years, higher levels of vitamin B₁₂ and holoTC were associated with decreased rate of total brain tissue volume (TBT) loss (p<0.001; p=0.002, respectively).
• Increased levels of vitamin B₁₂ and holoTC were also associated with less progression in CSF volume and tended to have an association with decreased loss of WMV.
• Besides increased levels of vitamin B₁₂, increasing age and history of cardiovascular conditions were associated with loss of TBT volume (p<0.001; p=0.02, respectively).

Total Homocysteine (tHcy)

• A significant cross-sectional association was observed between elevated levels of tHcy and TBT volume (p<0.001).
• In the longitudinal analysis over 6 years, increased levels of tHcy were associated with increased rate of loss of TBT volume (p=0.02).
• Also, higher tHcy levels were associated with higher CSF volume and increased rate of loss of GMV.

RBC Folate or Other Sulfur Amino Acids

• No significant cross-sectional or longitudinal associations were observed for RBC folate or other sulfur amino acid levels.

Association of Concentrations of Vitamin B12, Folate, and Sulfur Amino Acids with WMH Volume

• In all participants, no longitudinal association was found between vitamin B₁₂, RBC folate, or sulfur amino acid levels and the change in WMH volume over 6 years.
• Higher levels of tHcy were significantly associated with the progression of WMH volume (p=0.047) among individuals with systolic blood pressure higher than 140 mm Hg at baseline.

Conclusion

• Over a period of six years, a significant association was found between higher levels of vitamin B₁₂ or holotranscobalamin and decreased rate of brain volume loss in older adults without dementia. On the other hand, elevated levels of total homocysteine were associated with increased rate of brain volume loss.
• Vitamin B₁₂ and total homocysteine might thus be independent predictors of markers of brain aging in elderly people without dementia.
• Evidence from further trials is needed to validate that vitamin B₁₂ supplementation will reduce the rate of loss of total brain tissue volume in older adults with low-normal levels of vitamin B₁₂.

JAMA Psychiatry. 2016; 73 (6): 606-13.