Iron intake, brain iron, and Alzheimer's disease among community‐dwelling older adults. (31st December 2021)

• Record Type: Journal Article
• Authors: Agarwal, Puja; Ayton, Scott; Wang, Yamin; Agrawal, Sonal; Bennett, David A; Barnes, Lisa L; Leurgans, Sue E; Bush, Ashley I; Schneider, Julie A
• Is Part Of: Alzheimer's & dementia. Volume 17(2021)Supplement 10
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-12-31
• Subjects: Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1002/alz.055855
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: Background: Iron is an essential trace metal for brain health but maybe damaging when in excess, for example, through the regulated cell death program, ferroptosis. We earlier reported that higher brain iron levels are associated with faster cognitive decline and more neurofibrillary tangles, but the cause of iron elevation is unknown. This study investigates dietary and demographic factors associated with brain iron levels, Alzheimer's Disease (AD) pathology, and cognitive decline. Method: The study was conducted in 614 decedents (age‐at‐death:91.2±7.2years; education:14.6±3years;70% females) of the Rush Memory and Aging Project. AD pathology was assessed using standard criteria. Brain iron levels were evaluated in four brain regions (inferior temporal, mid frontal, and anterior cingulate cortices, and cerebellum) using Inductively Coupled Plasma Mass Spectrophotometry, and a composite mean z‐score was generated. Cognitive performance measured with 19 tests examined annually until death. Mean annual dietary iron intake was obtained from a validated food frequency questionnaire. Linear and logistic regression models with stepwise selection were used to investigate associations. Result: The mean dietary iron intake (up to>10 years of follow‐up before death) was not associated with postmortem brain iron levels, cognitive decline, or global AD pathology. Age‐at‐death (β=‐0.01, p=0.001), sex (β=0.30, p<0.0001), smoking (β=‐0.20, p=0.0008), and APOE‐ε 4 status (β=1.65, p=0.01) were each associated with higher brain iron levels. Except for APOE‐ε 4 status, these associations were retained when further controlled for AD pathology. Among dietary factors, in the age‐adjusted model, total fat (β=0.007, p=0.04) was positively, and omega‐3 fat (β=‐0.18, p=0.001) was negatively associated with higher brain iron levels. However, with further adjustment for age, sex, smoking, and APO‐ε 4 status, only the omega‐3 association, was retained. Conclusion: Unlike brain iron, dietary iron intake does not relate to AD pathology or cognitive decline. This may not be surprising since the blood‐brain barrier is relatively impermeable to fluctuations in blood iron levels. Brain iron accumulation in older adults relates to demographic factors independent of AD pathology. Overall, brain iron was not associated with dietary iron but was inversely associated with omega‐3 fats. Further studies on fat intake, dietary fat and iron interaction, and its relationship with brain measures are warranted.