Summary: A recent study indicates that even low levels of vitamin B12, while still considered normal, could lead to cognitive decline in older adults. Researchers discovered that seniors with diminished biologically active B12 experienced slower cognitive processing and an increased number of white matter lesions, despite meeting existing nutritional guidelines.

This research highlights a potential need to redefine B12 deficiency, suggesting a shift towards assessing functional biomarkers rather than sticking to rigid numerical thresholds. The authors advocate for additional investigations and consider the prospect of supplementation for older individuals to mitigate the risk of cognitive issues.

Key Findings

• Minor Cognitive Decline: Seniors with lower active B12 levels performed poorer in cognitive assessments focused on processing speed and reaction times.
• Brain Damage: MRI evaluations showed a higher prevalence of white matter lesions in those with reduced B12 levels, which may elevate the risk of dementia and stroke.
• Reevaluating B12 Recommendations: The study’s authors propose that current dietary guidelines for B12 could be inadequate for staving off neurological degeneration and may need to be reevaluated.

Source: UCSF

Merely meeting the basic requirement for vitamin B12, which is essential for DNA synthesis, red blood cell formation, and nerve health, may not suffice, particularly for older individuals. This inadequacy could expose them to cognitive impairments.

Conducted by researchers at UC San Francisco, the study found that older, healthy participants who had lower levels of B12, though still within the normal range, exhibited signs of neurological and cognitive decline.

Video Credit: Neuroscience News

This research established a connection between lower B12 levels and damage to white matter—the brain’s nerve fibers, which are critical for communication between brain regions. Participants with decreased B12 also displayed slower cognitive and visual processing speeds compared to those with higher levels.

Published in the Annals of Neurology on February 10, the study was led by Dr. Ari J. Green from UCSF’s Departments of Neurology and Ophthalmology, along with the Weill Institute for Neurosciences. The findings sparked discussions regarding the adequacy of current B12 standards and indicated a need for adjustment.

“Previous investigations defining healthy B12 levels might have overlooked subtle functional effects of varying B12 levels, which can influence individuals without obvious symptoms,” explained Dr. Green, who pointed out that well-established deficiencies typically relate to a type of anemia.

“By redefining B12 deficiency to consider functional biomarkers, we could facilitate earlier interventions and help prevent cognitive decline.”

Impact of Lower B12 on Cognitive Function

The study involved 231 healthy participants free from dementia or mild cognitive impairment, with an average age of 71. The participants were selected from the Brain Aging Network for Cognitive Health (BrANCH) study at UCSF.

Participants had a median B12 concentration of 414.8 pmol/L, significantly above the U.S. minimum threshold of 148 pmol/L. After adjusting for variables like age, sex, education, and cardiovascular risk factors, researchers focused on the biologically active form of B12, which more accurately reflects the vitamin’s availability for bodily use.

Cognitive testing revealed that those with lower active B12 levels exhibited slower processing speeds, signifying more subtle cognitive decline, particularly pronounced in older individuals. They also showed delays in visual response times, indicating a lag in visual processing and overall brain functionality.

MRI scans indicated a greater volume of lesions in the participants’ white matter, linked to risks of cognitive decline, dementia, or stroke.

Although the study’s participants were seniors with a specific vulnerability to low B12 levels, co-first author Alexandra Beaudry-Richard, MSc, noted that diminished B12 could “impact cognitive functions more significantly than previously assumed, affecting a broader segment of the population than recognized.”

Beaudry-Richard is pursuing her doctorate in research and medicine at UCSF’s Department of Neurology and University of Ottawa’s Department of Microbiology and Immunology.

“In addition to redefining B12 deficiency, healthcare providers should consider supplementation for older individuals presenting neurological symptoms, even if their B12 levels fall within normal parameters,” she emphasized.

“Ultimately, further research into the biological mechanisms of B12 insufficiency is vital, as it may serve as a preventable contributor to cognitive decline.”

Authors: Co-first author Ahmed Abdelhak, MD, PhD, is affiliated with the UCSF Department of Neurology and the Weill Institute for Neurosciences. For a complete list of authors, please refer to the study.

Funding and Disclosures: Supported by the Westridge Foundation and the Canadian Institutes of Health and Research. No conflicts of interest were disclosed.

About this Research on Cognitive Decline

Author: Suzanne Leigh
Source: UCSF
Contact: Suzanne Leigh – UCSF
Image: Credit to Neuroscience News

Original Research: Open access.
“Vitamin B12 Levels Association with Functional and Structural Biomarkers of Central Nervous System Injury in Older Adults” by Ari J. Green et al. Annals of Neurology

Abstract

Vitamin B12 Levels Association with Functional and Structural Biomarkers of Central Nervous System Injury in Older Adults

Objective

Vitamin B12 (B12) is essential for metabolizing fatty and amino acids as well as nucleotide synthesis. While the connection between B12 deficiency and neurological dysfunction is well established, the precise threshold for adequacy remains unclear concerning functional impairment and indications of injury. This research aims to evaluate whether B12 levels within the current normal range among healthy older adults are associated with measurable neurological injury or dysfunction.

Methods

In this study, we enrolled 231 healthy older volunteers (median age 71.2 years) with a median B12 blood concentration of 414.8 pmol/L, as determined by automated chemiluminescence assays. We conducted multifocal visual evoked potential testing, processing speed assessments, and magnetic resonance imaging to evaluate neurological status. Furthermore, we measured serum biomarkers indicative of neuroaxonal injury, astrocytic involvement, and amyloid pathology.

Results

Lower levels of B12 (log-transformed), especially reduced holo-transcobalamin, correlated with delays in visual evoked potential latency (estimate = −0.04; p = 0.023), processing speed deficits (in an age-dependent manner; standardized β = −2.39; p = 0.006), and larger white matter hyperintensities on MRI (β = −0.21; p = 0.039). Interestingly, elevated holo-haptocorrin (the biologically inactive B12 form) was associated with serum Tau levels, a neurodegeneration biomarker (β = 0.22, p = 0.015).

Interpretation

Findings highlight that healthy older adults may manifest neurological changes at both low and high extremes of the “normal” B12 range. This research challenges our conventional understanding of optimal serum B12 levels and suggests a need for reevaluation of nutritional guidelines.