Thirty-five cohort studies (14,325 participants, range 24 to 1,405) were included in the review. Follow-up ranged from 0.5 to 35 years. Twenty-one studies were considered to be of positive quality, 10 neutral quality, and four negative quality.
Of the 21 positive-quality studies, seven reported positive associations between vitamin B12 status and cognitive decline, dementia or Alzheimer's disease, and 14 studies did not. Nineteen of the 21 positive-studies used serum vitamin B12, of which three studies reported significant associations with cognitive decline. All four studies with positive-quality that used the methylmalonic acid markers and holotranscobalamin markers reported significant associations with cognitive decline, dementia or Alzheimer's disease.
Cognitive decline and vitamin B12 status in non-demented participants: Four of six studies reported no association between cognitive decline and serum vitamin B12 after a mean follow-up of 5.1 years.
Cognitive decline and vitamin B12 status in participants with unspecified cognition: Four of 11 studies reported an association between vitamin B12 status and at least one test of cognition. Seven studies found no association between 2.3 and 6.0 years follow-up.
Cognitive decline in participants with existing dementia: All five studies reported no association between vitamin B12 and cognition.
Development of dementia in participants with no dementia at baseline: Five of eight studies reported no association between serum vitamin B12 and the development of dementia. Five of eight studies reported no association between holotranscobalamin or serum vitamin B12 alone or in combination with low serum folate concentrations and the development of Alzheimer's disease.