(PTFS10-02-26) Association of Nutrient Intake and Complete Blood Count With Brain Iron Levels by Alzheimer’s Disease Status Among Community-Dwelling Older Adults

Objectives: Iron is an essential metal for brain health, but excess may regulate cell death program, ferroptosis by promoting lipid peroxidation. We earlier reported that higher brain iron levels are associated with increased cognitive decline and Alzheimer’s Disease (AD) pathology. The cause of iron accumulation is unknown. This study investigates dietary factors, and blood-count measures associated with brain iron levels, and if these associations vary by AD status.

Methods: The study included 503 autopsied participants (age-at-death:91.2±7.2years; education:14.6±3years;70% females) of the Rush Memory and Aging Project. Calorie-adjusted nutrient intake (derived from validated food frequency questionnaire) and complete blood count was averaged from the years of follow-up before death (6.7 ± 3.8 years). Structured clinical neurological examination (using battery of 19 cognitive tests) and standardized diagnostic criteria defined dementia and AD pathology. Brain iron was evaluated in four brain regions (inferior temporal, midfrontal, and anterior cingulate cortices, and cerebellum) using ICP-MS, a composite score was generated. Linear regression models were used, and interactions were tested by AD diagnosis group a) no dementia or AD pathology (n=155), b) no dementia but presence of AD pathology (n=169), c) dementia with AD pathology (n=179).

Results: In separate models when controlling for age at death, sex, education and APOE-ε 4 status, higher vitamin B12 (β=-0.0001,p=0.039) and omega-3 (β=-0.014,p=0.010), not dietary iron ((β=-0.0002,p=0.477) were associated with lower brain iron levels. These associations were retained after controlling for AD pathology. Overall higher mean corpuscular volume (β=0.0025,p=0.003) was associated with elevated brain iron levels. However, hematocrit association with brain iron differed by diagnosis group (p-for-interaction < 0.05).

Conclusions: Dietary iron does not relate to brain iron, however, higher vitamin B12 and omega-3 intake may lower brain iron accumulation in older adults. Although the blood-brain barrier is relatively impermeable to fluctuations in blood, it is damaged in AD and may contribute to our findings. Further research is needed on dietary factors for its role in maintaining essential nutrients and lipids in the aging brain.

Funding Sources: NIH/NIA