Boosting brain health with iron and manganese: A dietary defense against cognitive decline

By Hugo Francisco de SouzaReviewed by Susha Cheriyedath, M.Sc.Oct 25 2023

In a recent study published in the journal Nutrients, researchers investigated the association between dietary mineral consumption and cognitive impairment (CI) risk in elderly Spanish individuals. CI classification was carried out using the Montreal Cognitive Assessment (MoCA) test, a highly sensitive and specific yet rarely used methodology. Study findings revealed that 54.2% of the 201 participants presented CI (MoCA < 26). Increased iron and manganese intake in women reduced CI risk in women. However, no association between mineral intake and CI could be established in men.

Study: Association between Mineral Intake and Cognition Evaluated by Montreal Cognitive Assessment (MoCA): A Cross-Sectional Study. Image Credit: Created with the assistance of DALL·E 3

Can we use diet to combat neurodegeneration?

Modern medicine has lengthened human life expectancy, increasing the manifestation of age-associated chronic conditions, including cancers, cardiovascular disorders, and neurodegenerative diseases. Dementia, a group of neurological conditions characterized by memory loss and other severe thinking disorders, is one of the most common ailments in older adults. It is estimated to affect 50 million individuals globally, with an additional 10 million patients yearly.

The role of MCI in dementia

Dementia pathology often begins as mild cognitive impairment (MCI), identified by subjective expert observation and objective comparisons with a patient’s prior level of functioning. While MCI may be delayed by behavioral and lifestyle changes (diet, hypertension therapy, cognitive stimulation), no pharmacologically approved ‘cures’ for the condition exist. MCI patients over 65 years of age are at a 5-fold greater risk of developing dementia (especially Alzheimer’s disease [AD]) compared to adults without MCI.

Lifestyle interventions: A glimmer of hope

Studies report that over 50% of patients with MCI progress to dementia within five years of MCI development, leading experts to consider MCI the critical stage for modifiable lifestyle interventions, which may delay or even reverse MCI before the onset of AD. Physical activity, cessation of smoking/alcohol consumption, and dietary interventions remain the best studied of these interventions.

Neurological benefits of diet

Dietary patterns with beneficial neurological associations have been identified, including the Mediterranean diet, the Dietary Approach to Stop Hypertension (DASH), and the Mediterranean–DASH Diet Intervention for Neurodegenerative Delay (MIND). Research on the link between neurology and diet has focused on clinical outcomes, with limited evidence for the mechanistic influences of biomolecules and individual dietary components such as vitamins, minerals, and fatty acids.

Minerals, including iron, copper, zinc, magnesium, manganese, and selenium, have been suggested to have associations with cognitive functioning, given their role in DNA repair and their antioxidative properties. However, this hypothesis has not been formally tested within a structured scientific framework.

Study design and methods

In the present study, researchers tested the associations between dietary mineral intake and cognitive impairment. Participants for the study were recruited from the “Cognitive and neurophysiological characteristics of people at high risk for the development of dementia: a multidimensional approach” (COGDEM) cohort. The cross-sectional study initially comprised 262 Spanish individuals, of which 201 met the inclusion criteria. Inclusion criteria included baseline Mini-Mental State Examination (MMSE) scores ≥ 24 and a Geriatric Depression Scale (GDS) Short-Form score ≤ 5.

Data collection and evaluation

Data collected from the study cohort included health and socio-demographic data, three-day food consumption records (diet), anthropometric data, physical activity measurements, genotyping, and neuropsychological evaluations.

Health and socio-demographic data were collected via a questionnaire that recorded employment status, education level, and chronic medical conditions (especially depression, hypertension, and diabetes). Food record data was collected using the DIAL nutritional analysis software. Nutrients of interest included energy (kcal/day), magnesium (mg/day), iron (mg/day), copper (µg/day), selenium (µg/day), manganese (mg/day), and zinc (mg/day). Minerals were standardized to calorific intake using the Willett residual model. Dietary reference intakes (DRIs) were used to compute relative mineral contributions.

Anthropometric data comprised weight, height, and body mass index (BMI) collected per The International Society for the Advancement of Kinanthropometry (ISAK) guidelines. Physical activity data was collected using a right-hip-attached accelerometer over seven days.

Genotyping was performed to identify and investigate the Apolipoprotein E (APOE) allele in participants (i.e., rs7412 and rs429358 polymorphisms). Based on genotyping results, individuals were categorized as carriers (APOE ε4+) or non-carriers (APOE ε4−) of the ε4 allele. This allele is strongly associated with AD.

Neuropsychological tests comprised the GDS test for depression, the MMSE to evaluate immediate memory, attention, calculation ability, and language, and the Montreal Cognitive Assessment (MoCA).

“The MoCA is a cognitive screening tool to assist in detection of mild cognitive impairment (MCI) [37]. This test has been validated for the Spanish population. This test studies different abilities such as attention, concentration, memory, language and executive functioning.”

 MoCA is a 30-point test with scores < 26 suggesting MCI. Since no clinical evaluation of MCI was included in this study, MoCA < 26 was taken as the MCI classification criteria.

Key study findings

Of the 201 participants included in the study, 63.2% were female, with a mean age of 59.8 years. MoCA evaluations identified 54.3% of participants as having MCI (34.3% females and 19.9% males). Education status was the only non-dietary variable observed to play a role in CI – the higher the education status, the lower the probability of MCI. Other anthropometric, exercise, and genotyping results did not depict statistically significant associations with CI risk.

The most significant dietary associations were the daily recommended intake (DRI) contributions of iron and manganese in women – higher intakes of these minerals were associated with lower CI prevalence. Copper DRI contributions in women were also positively correlated with beneficial CI outcomes, though this interaction was not as significant as those for iron and manganese.

Gender-specific results

Surprisingly, no associations could be made between any dietary minerals and positive CI outcomes in male participants.

Concluding remarks and future directions

The present study investigates the association between common dietary minerals and cognitive impairment as measured by the MoCA test. Results highlight the importance of high iron and manganese consumption, especially in women. These minerals, and to a lesser extent, copper, confer a protective effect against MCI progression and AD onset. No associations between mineral intake and cognition could be found in men.

“Intervention and follow-up studies monitoring dietary intake and nutritional status (including biochemical parameters) are needed to confirm the possible protective effect of iron and manganese intake on cognitive impairment and to take a deeper look at the differences found in these associations between mineral intake and cognitive function according to sex.”