What is the relationship between Vitamin B12 (Cobalamin) deficiency and dementia?

From the Guidelines

Vitamin B12 supplementation should not be offered to persons with dementia unless there is an indication of deficiency, as it does not appear to prevent or treat dementia in those with normal B12 levels. According to the most recent and highest quality study 1, persons with dementia should not be offered micronutrient supplements, including vitamin B12, unless there is an indication of deficiency. This recommendation is based on the lack of evidence demonstrating a cognitive benefit from supplementing a single nutrient, including vitamin B12, in persons with dementia.

Key Points to Consider

• Vitamin B12 deficiency can contribute to cognitive decline and dementia-like symptoms, which may be reversible with proper treatment 1.
• Normal B12 levels range from 200-900 pg/mL, with levels below 200 pg/mL indicating deficiency.
• Treatment of vitamin B12 deficiency typically involves supplementation, with dosages varying based on severity, such as oral supplements of 1,000-2,000 mcg daily for mild deficiency or B12 injections for severe deficiency 1.
• Elderly individuals, strict vegetarians/vegans, and those with absorption issues are at higher risk of vitamin B12 deficiency.
• Maintaining adequate B12 levels through diet or supplements is an important preventive measure for brain health, but supplementation should only be considered in cases of deficiency, as recommended by the most recent guidelines 1.

Recommendations for Practice

• Check B12 levels in persons with dementia if deficiency is suspected.
• Treat vitamin B12 deficiency according to established guidelines, such as those provided by NICE 1.
• Do not offer vitamin B12 supplementation to persons with dementia without an indication of deficiency, based on the recommendation from the most recent ESPEN guideline update 1.

From the Research

Relationship Between B12 and Dementia

• The relationship between vitamin B12 deficiency and dementia is complex, with some studies suggesting a link between the two 2, 3.
• Evidence is convincing that hyperhomocysteinemia, with or without hypovitaminosis B12, is a risk factor for dementia 2.
• However, in the absence of hyperhomocysteinemia, evidence is less convincing that hypovitaminosis B12 is a risk factor for dementia 2.

Diagnosis and Treatment of B12 Deficiency

• Assessing serum B12 and treatment of B12 deficiency is crucial for those cases in which pernicious anemia is suspected and may be useful for mild cognitive impairment and mild to moderate dementia 2.
• The serum B12 level is the standard initial test, with 200 picograms per milliliter or less considered low, and 201 to 350 picograms per milliliter considered borderline low 2.
• Other tests may be indicated, including plasma homocysteine, serum methylmalonic acid, antiparietal cell and anti-intrinsic factor antibodies, and serum gastrin level 2.
• Oral cyanocobalamin is generally favored over intramuscular cyanocobalamin 2, 4.

Effects of B12 Treatment on Dementia

• Some patients without pernicious anemia, but with B12 deficiency and either mild cognitive impairment or mild to moderate dementia, might show some degree of cognitive improvement with supplemental B12 treatment 2, 3.
• However, evidence that supplemental B12 treatment is beneficial for patients without pernicious anemia, but with B12 deficiency and moderately-severe to severe dementia is scarce 2, 3.
• Vitamin B12 treatment may improve frontal lobe and language function in patients with cognitive impairment, but rarely reverses dementia 3.

Prevention of Dementia and Stroke

• Metabolic vitamin B12 deficiency is common, being present in 10%-40% of the population, and contributes importantly to cognitive decline and stroke in older people 5.
• Measuring serum B12 alone is not sufficient for diagnosis; it is necessary to measure holotranscobalamin or functional markers of B12 adequacy such as methylmalonic acid or plasma total homocysteine 5.
• B-vitamin therapy with cyanocobalamin reduces the risk of stroke in patients with normal renal function, but is harmful in patients with renal impairment 5.
• Methylcobalamin may be preferable in renal impairment, and future research is needed to distinguish the effects of thiocyanate from cyanocobalamin on hydrogen sulfide, and effects of treatment with methylcobalamin on cognitive function and stroke 5.