More evidence is needed. Iron, incident cognitive decline and dementia: a systematic review

Background: Our aim was to systematically review the relationship between iron and incident cognitive decline or dementia from midlife onwards. Methods: Systematic review of eligible studies using Medline, Embase and PsycINFO^® for the period from 1 January 1986 to 2 December 2016 (CRD42016023800), where study populations had a mean age of over 50 years and were free of cognitive impairment or dementia at baseline. Two authors independently extracted data according to eligibility criteria and assessed study characteristics, quality and outcomes. Disagreement was resolved by discussion. Results: A total of 1185 relevant records were identified with 12 full-text articles eligible for review. Six studies were excluded, leaving six texts to be included. Sample size ranged from 90 to 7173, with an average follow up of approximately 11.5 years. Baseline iron measures included brain iron (n = 2), iron-related biomarkers in blood and plasma (n = 2), and iron intake estimates from dietary records (n = 2). Outcomes were dementia incidence (n = 2) and longitudinal outcomes on neuropsychological tests (n = 4). Bias was evident across studies in one or more of the following: recruitment, iron exposure, outcome assessments, potential confounders, missing data or attrition. Conclusions: Diversity across the small number of identified studies precludes conclusions regarding the role of iron in cognitive decline or dementia. Our review highlights substantial gaps in the evidence base and the need for more comprehensive, higher quality studies in this area.