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Magnesium Emerges as a Powerful Brain Protector With Larger Brain Volumes and Lower Dementia Risk

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From Brain Shrinkage to Prevention: Why Magnesium Matters for Dementia Risk

Dementia has emerged as one of the most pressing global health challenges, affecting an estimated 55 million people worldwide and imposing substantial personal, social, and economic burdens on aging societies. As disease-modifying pharmacotherapies for Alzheimer’s disease and related dementias continue to show modest and context-dependent benefits in real-world practice, strategic emphasis is shifting toward prevention, early risk stratification, and aggressive modification of vascular and metabolic drivers across the life course.

Within this preventive framework, micronutrient status has gained attention as a potentially modifiable determinant of brain resilience with magnesium standing out due to its central role in over 300 enzymatic reactions, ATP metabolism, membrane stability, and the regulation of neuronal excitability, synaptic plasticity, vascular tone, and inflammatory pathways. Converging line of evidence from epidemiological cohorts, neuroimaging analyses, and early interventional studies now suggest that higher magnesium exposure within physiological ranges, primarily from diet, and in some cases supported by supplementation may be associated with preserved brain volume healthier white matter and a lower risk of cognitive and dementia.

Dementia as a Metabolic-Neuroinflammatory Disease, Not Just “Memory Loss”

Dementia is now widely framed as the clinical end-stage of decades of interacting metabolic vascular, and neuroinflammatory insults layered onto genetic susceptibility and normal aging processes. Rather than a purely “neurodegenerative” phenomenon occurring in isolation, converging data from imaging, fluid biomarkers, and neuropathology support a model in which impaired brain energy metabolism, small-vessel disease, and chronic glial activation progressively erode synaptic integrity and network connectivity [1,2,3,4,5].

Within this framework, insulin resistance, endothelial dysfunction, oxidative stress, and low-grade systemic inflammation are key upstream processes that converge on hippocampal and association cortices, promoting synaptic loss, white-matter damage, accelerated brain atrophy, and cognitive decline. Mixed Alzheimer, vascular pathology is common in older adults, underscoring how metabolic and vascular injury amplify amyloid and tau-related neurotoxicity and help drive the transition from preclinical disease to overt dementia [4,5,6].

Epidemiologic syntheses, including the Lancet Commission reports and subsequent and subsequent updates, consistently identify a cluster of modifiable risk factors such as hypertension, type 2 diabetes, dyslipidemia, obesity, physical inactivity, poor diet quality, smoking, depression, hearing loss, ad low social contact that together account for a substantial proportion of dementia cases at the population level. These risk factors often co-occur along social gradients and across the life course emphasizing the need for integrated cardiometabolic, mental health, sensory and lifestyle interventions in dementia prevention [7,8,9,10,11,12].

Against this complex pathophysiologic background, micronutrient adequacy has emerged as a potentially modifiable layer influencing neurovascular resilience and inflammatory tone, with magnesium receiving particular attention. Experimental and translational studies indicate that magnesium supports mitochondrial function, stabilizes neuronal and endothelial membranes, antagonizes excessive calcium influx, and attenuates NF-kB – mediated pro-inflammatory signalling, thereby offering a biologically plausible means of modulating neurodegeneration and dementia trajectories within broader multimodal prevention strategies [13,14,15,16].

Magnesium: The Under-Recognized Mineral Powering Neurons and Synapses

The recent review by Patil and colleagues synthesizes observational and neuroimaging findings linking high dietary magnesium intake to slower brain aging and reduced dementia risk, with particularly pronounced effects in postmenopausal women. Drawing primarily on UK Biobank data from 6,001 cognitively healthy adults aged 40-73 years, the authors report that individuals consuming more than 550 mg/day of magnesium exhibited brain volumes approximately one year younger by age 55 compared with those consuming the population average of 350 mg/day. This association was most evident in gray matter and hippocampal regions, structures central to memory encoding and executive function, and was robust to adjustment for education, physical activity, and cardiometabolic comorbidities [16,17,18,19].

The magnesium-dementia relationship appears to follow a U-shaped pattern at the serum level, in which both low (<0.79mmol/L) and high (³ 0.90 mmol/L) concentrations are associated with elevated risk, with the lowest hazard observed around 0.83 mmol/L. A large Dutch prospective cohort found that individuals at the extremes of serum magnesium faced a 28-30% increased dementia risk over nearly eight years of follow-up, underscoring the importance of distinguishing physiological sufficiency from deficiency or pharmacologic excess. These findings suggest that targeting mid-rage magnesium status, achievable through whole-food dietary sources rather than aggressive supplementation may confer the greatest cognitive protection [16,20,21,22,23].

Particularly striking are the sex-specific and menopause-related effects documented in the UK Biobank cohort. Postmenopausal women consuming higher baseline magnesium (every 1 mg above 350 mg/day) showed 0.4% larger gray matter, 1.09% larger white matter, and 1.5% larger hippocampal volumes relative to premenopausal women, alongside significantly lower white‑matter lesion burden. Latent trajectory analyses revealed that women following a “high‑decreasing” magnesium intake pattern over time maintained larger white‑matter volumes and fewer lesions than their premenopausal counterparts, whereas those on a “low‑increasing” trajectory accumulated more white‑matter lesions after menopause. The authors hypothesize that magnesium’s anti‑inflammatory and vasodilatory properties may partially compensate for the loss of estrogen’s neuroprotective and endothelial effects during the menopausal transition, when neuroinflammatory markers and vascular risk factors typically rise [16,17,24,25,26].

Mechanistically, Patil and colleagues emphasize magnesium’s multifaceted neuroprotective roles: voltage‑dependent blockade of NMDA receptors to prevent calcium‑mediated excitotoxicity; suppression of pro‑inflammatory cytokines (IL‑6, TNF‑α, CRP) and microglial over‑activation; stabilization of blood–brain barrier integrity; natural calcium‑channel antagonism to promote cerebral vasodilation and perfusion; enhancement of antioxidant enzyme activity (superoxide dismutase, glutathione peroxidase); mitochondrial membrane stabilization; and support for hippocampal long‑term potentiation underlying synaptic plasticity and memory formation. These converging pathways position magnesium as a biologically plausible modulator of both Alzheimer and vascular dementia pathologies, though the relative contributions of each mechanism in humans remain to be precisely quantified [13,14,16].

The review acknowledges significant limitations inherent to observational designs, including residual confounding by overall diet quality, physical activity, socioeconomic status, and genetic factors, as well as potential reverse causation wherein cognitive decline may lead to poorer dietary choices. Dietary assessment via 24‑hour recall is subject to measurement error and may not reflect long‑term habitual intake or account for magnesium bioavailability from different food matrices. Importantly, the absence of large‑scale, long‑duration randomized controlled trials limits causal inference and precludes definitive dose–response guidance for dementia prevention. Future research priorities include adequately powered RCTs with standardized cognitive endpoints and neuroimaging measures, exploration of formulation‑specific effects (for example, magnesium L‑threonate versus citrate versus oxide), and investigation of gene–nutrient interactions and precision nutrition approaches tailored to baseline magnesium status, menopausal stage, and cardiometabolic phenotype [16,20].

High-Magnesium Diets, Younger-Looking Brains, and Lower Dementia Risk

Observational neuroimaging and cohort data increasingly support an association between higher magnesium intake, more favourable brain structure, and lower risk of late‑life cognitive decline, particularly in women. These findings are inherently non‑causal but help define physiologically relevant intake ranges and populations who may derive the greatest neuroprotective benefit.

A large neuroimaging analysis using UK Biobank data (n = 6001; age 40–73 years) from the Australian National University group showed that higher dietary magnesium intake was associated with larger total gray and white matter volumes and lower white‑matter lesion burden in mid‑ to late‑adulthood. Individuals with magnesium intakes in the highest range (around 550 mg/day) had “younger‑appearing” brains, equivalent to roughly one year less brain aging by age 55 compared with those consuming the population average of about 350 mg/day, with the association being most pronounced in women and in those with higher baseline intake. Sex‑stratified latent class analyses further indicated that women following consistently high or high‑decreasing magnesium trajectories over time had larger hippocampal volumes and fewer white‑matter lesions than those with low or increasing but still lower intakes, suggesting that sustained exposure in the perimenopausal and postmenopausal years may be particularly relevant [17,27].

Prospective data from the Women’s Health Initiative Memory Study (WHIMS), which followed more than 6000 postmenopausal women, found that total magnesium intake (dietary plus supplemental) in the range between the estimated average requirement and recommended dietary allowance was associated with a lower risk of incident mild cognitive impairment and probable dementia. Risk reduction was strongest in the middle quintiles of total magnesium intake, and model fit was improved by a quadratic (curvilinear) term, indicating a non‑linear or U‑shaped relationship rather than a simple “more is better” pattern. Women in the third to fifth quintiles (roughly 257–>398 mg/day) had significantly lower hazards of MCI compared with the lowest quintile, whereas very low and very high intakes conferred less advantage, aligning with serum data that suggest both deficiency and excess magnesium may be unfavourable for brain health [28].

Complementary evidence from a nationally representative US sample (NHANES 2011–2014) showed that higher total magnesium intake was independently associated with better global cognition scores in adults aged ≥60 years, even after adjustment for sociodemographic, lifestyle, and clinical covariates. Subgroup analyses revealed that the protective association was particularly evident among non‑Hispanic White participants, women, and individuals with sufficient serum 25‑hydroxyvitamin D levels, suggesting possible interaction between magnesium intake, vitamin D status, and ethnicity‑related or social determinants of health factors. Across these observational datasets, higher magnesium intake within physiological ranges consistently aligns with larger brain volumes, fewer white‑matter lesions, and better cognitive performance, but the non‑linear patterns and effect modification underscore the need for cautious interpretation and for randomized trials to test whether actively optimizing magnesium intake can modify dementia risk trajectories [17,20,28,29,30,31].

When More Is Not Always Better: The U-Shaped Magnesium- Cognition Curve

Recent evidence on serum magnesium and cognitive outcomes supports a nuanced, non‑linear relationship rather than a simple “more is better” paradigm. A 2024 systematic review and meta‑analysis pooling three randomized controlled trials and twelve cohort studies reported insufficient and heterogeneous data to draw firm conclusions about magnesium supplementation per se, but identified a consistent U‑shaped association between serum magnesium and risk of all‑cause dementia and cognitive impairment across prospective cohorts. In these analyses, the lowest dementia risk clustered around serum magnesium concentrations of approximately 0.85 mmol/L, with risk rising at both low and high ends of the reference interval (roughly 0.75–0.95 mmol/L) [20].

Population‑based cohort data illustrate this pattern in more detail. In the Rotterdam Study (n ≈ 9500; mean age 65 years), both low (≤0.79 mmol/L) and high (≥0.90 mmol/L) serum magnesium levels were associated with about a 30% higher risk of all‑cause dementia compared with the mid‑range (0.80–0.89 mmol/L), even after extensive adjustment for cardiovascular risk factors, kidney function, comorbidities, and diuretic use. Similarly, the Atherosclerosis Risk in Communities (ARIC) cohort showed that individuals in the lowest quintile of midlife serum magnesium had a 24% higher incidence of dementia over more than two decades of follow‑up compared with those in the highest quintile, although serum magnesium was not clearly related to the subsequent rate of cognitive decline once dementia emerged. In hemodialysis populations, where magnesium handling is profoundly altered, a U‑shaped relationship between serum magnesium and mild cognitive impairment has also been reported, with the lowest MCI risk at intermediate concentrations and higher risk at both lower and higher levels [13,16,22,32,33].

These convergent findings underscore the need to differentiate between dietary magnesium intake within physiological ranges and pharmacologic or iatrogenic exposures that may drive serum concentrations outside the optimal window. In practical terms, most of the epidemiologic signal for cognitive benefit arises from maintaining serum magnesium near the mid‑normal range (around 0.85 mmol/L), typically achievable through magnesium‑rich diets and modest supplementation in individuals without major renal impairment. At the same time, clinicians and researchers must account for kidney function, concomitant medications (for example, diuretics, PPIs), and comorbidities when interpreting serum magnesium and cognitive risk, recognizing that both chronic hypomagnesemia and sustained hypermagnesemia may be detrimental to brain health. Within this framework, the emerging consensus is that optimal cognitive outcomes appear to cluster around a balanced magnesium status rather than at the extremes, reinforcing the concept of “right range” rather than maximal levels in dementia prevention strategies [20,32,33,34].

How Magnesium Guards the Aging Brain: From NMDA Receptors to Neuroinflammation

The neuroprotective effects of magnesium operate through multiple convergent mechanisms spanning excitotoxicity, neuroinflammation, mitochondrial energetics, and vascular–metabolic integrity, positioning magnesium as a plausible systems‑level modulator of dementia risk rather than a single‑pathway agent.

At the cellular level, magnesium acts as a physiological, voltage‑dependent blocker of the N‑methyl‑D‑aspartate (NMDA) glutamate receptor, antagonizing excessive calcium influx during normal resting membrane potentials and becoming unblocked only during appropriate depolarizations that mediate synaptic plasticity and learning. This unique property allows magnesium to prevent sustained NMDA receptor overstimulation and calcium‑mediated excitotoxicity, a final common pathway in ischemic, hypoxic and inflammatory brain injury without compromising physiological neurotransmission. Experimental models of hypoxia‑ischemia, traumatic brain injury, and glutamatergic excitotoxicity demonstrate that magnesium sulfate pretreatment reduces lesion size, attenuates apoptosis, and improves long‑term behavioural outcomes, effects largely attributable to limiting extracellular glutamate accumulation, blocking calcium‑dependent caspase activation, and stabilizing mitochondrial membrane potential [35,36,37,38].

Magnesium also exerts potent anti‑inflammatory effects by inhibiting nuclear factor kappa B (NF‑κB), the master transcription factor that drives the expression of pro‑inflammatory cytokines including tumor necrosis factor‑alpha (TNF‑α), interleukin‑1β (IL‑1β), and interleukin‑6 (IL‑6), as well as enzymes such as inducible nitric oxide synthase (iNOS) and cyclooxygenase‑2 (COX‑2). In primary microglia and in vivo models, magnesium reduces lipopolysaccharide (LPS)‑induced microglial activation, shifts microglia toward the M2 (anti‑inflammatory) phenotype, lowers the production of reactive oxygen species and prostaglandins, and attenuates the release of substance P and other inflammatory mediators. Magnesium deficiency, conversely, triggers microglial over‑activation and upregulates neuroinflammation‑associated genes in the hippocampus and cortex, effects that are reversed by magnesium repletion, highlighting the mineral’s tonic restraint on glial inflammatory tone [13,14,39,40].

Figure 1. The role of magnesium in the brain. Magnesium in the brain plays a fundamental role in the modulation of different pathways [14]

Within mitochondria, magnesium is a critical cofactor for the tricarboxylic acid (TCA) cycle and electron transport chain, regulating the activities of key enzymes and supporting ATP synthesis. Dysregulation of mitochondrial magnesium homeostasis impairs oxidative phosphorylation, reduces cytoplasmic ATP availability, and increases susceptibility to oxidative stress and apoptosis, whereas optimal intramitochondrial magnesium concentrations preserve membrane potential, enhance ATP export, and protect against metabolic failure under ischemic or inflammatory conditions. In oligodendrocytes, which have high metabolic demands for myelin synthesis and axonal support, adequate magnesium is essential for maintaining mitochondrial integrity and energy production, with disruption of mitochondrial magnesium uptake leading to impaired ATP generation, axonal demyelination, and increased vulnerability to hypoxic‑ischemic injury [13,38,41,42,43,44].

Beyond direct neurobiological actions, magnesium influences brain health indirectly through cardiometabolic pathways that are major drivers of vascular and Alzheimer‑type dementia. Magnesium improves insulin sensitivity, reduces hyperglycemia and hyperinsulinemia, and lowers the risk of type 2 diabetes, a condition strongly linked to brain glucose hypometabolism, amyloid‑beta accumulation, tau hyperphosphorylation, and accelerated cognitive decline (often termed “type 3 diabetes”). Magnesium supplementation in individuals with diabetes has been shown to enhance glucose transport, normalize lipid metabolism, and activate sirtuin 1 (Sirt1), an anti‑aging deacetylase that regulates mitochondrial function, reduces oxidative stress, and attenuates amyloid‑beta toxicity [45,46,47,48,49].

Magnesium also acts as a natural calcium‑channel blocker, promoting endothelial vasodilation, improving cerebral blood flow, and lowering systemic blood pressure, a leading modifiable risk factor for white‑matter lesions, brain atrophy, and dementia. Hypertension thickens cerebral arteriolar walls, reduces white‑matter perfusion, and accelerates demyelination in vulnerable watershed zones, whereas magnesium mitigates endothelial dysfunction, reduces oxidative stress, and preserves blood–brain barrier integrity under inflammatory and ischemic stress. Collectively, these converging pathways, NMDA receptor modulation, neuroinflammatory dampening, mitochondrial support, insulin sensitization, and vascular protection provides a mechanistic rationale for the epidemiologic associations between higher magnesium intake, preserved brain structure, and lower dementia risk observed in population studies [13,14,16,17,38,45,50].

Can Magnesium Supplementation Sharpen Cognition? Signals from Early Trials

Interventional studies of magnesium supplementation and cognition are fewer and more heterogeneous than the observational literature, but they collectively suggest a modest, domain‑specific signal of benefit rather than large global effects. In a 6‑week, double‑blind, randomized controlled trial in adults with self‑reported sleep complaints and suboptimal cognition, daily supplementation with magnesium L‑threonate (Magtein) led to significantly greater improvements in overall cognitive performance on the NIH Toolbox Total Cognition Composite compared with placebo, with particularly notable gains in working and episodic memory, faster reaction time, and an estimated 7.5‑year reduction in “cognitive brain age.” These cognitive changes were accompanied by improvements in sleep architecture and daytime functioning in a parallel trial, in which magnesium L‑threonate enhanced deep and REM sleep, mood, mental alertness, and daytime productivity versus placebo, supporting broader effects on neurophysiological recovery processes that underlie cognitive performance [51].

Beyond magnesium L‑threonate, several small RCTs and pilot trials using other oral magnesium formulations, including magnesium citrate or mixed magnesium salts, have reported improvements in global cognitive screening scores and specific executive functions, particularly in older adults with mild cognitive impairment or low baseline mineral intake. In one 12‑week double‑blind trial in adults over 65 years, magnesium supplementation at dietary reference intake levels produced a greater increase in Montreal Cognitive Assessment (MoCA) scores than placebo (mean change +2.3 vs +0.5 points), with the effect concentrated in the older subgroup. Open‑label work in patients with mild to moderate dementia treated for 8–12 weeks with a magnesium‑L‑threonate–containing compound showed increased red blood cell magnesium, improvements in a composite cognitive index, and regional cerebral metabolic changes on FDG‑PET, although sample sizes were small and statistical robustness limited. Overall, meta‑analytic synthesis of three double‑blind RCTs indicates a pattern consistent with small positive effects of magnesium on selected cognitive outcomes, but substantial heterogeneity in formulation, dose, duration, baseline magnesium status, and cognitive endpoints, as well as short follow-up and underpowered designs precludes definitive recommendations on optimal dosing, compound choice, or target populations for dementia prevention [20,52,53].

Translating the Data: Food-First Magnesium Strategies for Brain Longevity

For adults, most guidelines recommend a total magnesium intake of approximately 310–320 mg/day for women and 400–420 mg/day for men, with pregnancy increasing needs to around 350–360 mg/day. Observational data in cognitive and dementia research suggest that intakes at or modestly above these values, typically  achieved through magnesium‑dense dietary patterns rather than high‑dose supplements are associated with larger brain volumes, fewer white-matter lesions, and better cognitive performance in older adults [16,17,28,29,54].

From a practical standpoint, prioritizing food sources is the safest and most physiologically aligned strategy to achieve neuroprotective magnesium levels. Magnesium-rich foods include leafy green vegetables (for example, spinach, kale), nuts (almonds, cashews, Brazil nuts), seeds (pumpkin, hemp, chia, sesame), legumes (beans, lentils, chickpeas), and whole grains, all of which also provide fiber, polyphenols, and cardiometabolic benefits relevant to dementia prevention. In typical dietary patterns, one to two servings per day from each of these categories can readily supply 200–300 mg of magnesium, meaning that small, consistent shifts such as adding a handful of nuts, swapping refined grains for whole grains, and incorporating legumes several times per week can close much of the intake gap without reliance on high supplemental doses [54,55,56,57,58,59].

Supplementation becomes a reasonable adjunct in individuals with low dietary intake, increased losses (for example, due to diuretics or proton pump inhibitors), high cardiometabolic risk, or documented subclinical deficiency, but dosing should be individualized and kidney function always considered. Most authorities and safety reviews note that dose‑limiting side effects from oral magnesium, primarily osmotic diarrhea, loose stools, and abdominal cramping are more common with poorly absorbed salts (such as magnesium oxide) and at supplemental intakes above about 350 mg/day, whereas better‑absorbed forms (for example, magnesium citrate, glycinate, malate) may be better tolerated at equivalent elemental doses. In people with normal renal function, the kidneys can usually excrete excess magnesium, making serious hypermagnesemia from diet or moderate supplementation very rare; by contrast, in advanced chronic kidney disease (especially when creatinine clearance is <20 mL/min) or in those using high‑dose magnesium‑containing laxatives or antacids, accumulation can occur and lead to neuromuscular depression, hypotension, and arrhythmias, warranting lower doses, careful monitoring, or avoidance depending on stage of CKD [54,60,61,62,63,64,65].

Group/contextTypical target from all sources (mg/day)Practical approach and cautions
Adult women (non-pregnant)310-320 [54,59]Emphasize leafy greens, nuts, seeds, legumes; light supplementation if diet remains inadequate.
Adult men400-420 [54,59]Similar food‑first strategy; consider 100–200 mg supplemental if intake is consistently low.
Older adults with low intake or high riskRDA-slightly above (»350-450) [16,29]Food‑first plus low‑to‑moderate doses; monitor bowel tolerance and medications
CKD stage 4-5 or dialysisIndividualized; often at or below RDA [61,64]Avoid high‑dose OTC magnesium; if used, tightly supervised with serum monitoring.

Table 1. Typical Intake vs Guidance

Leveraging AI and Metabolic Profiling to Personalize Magnesium for Brain Health

Magnesium lies at a critical intersection of metabolic, vascular, and neuroinflammatory biology, which makes its adequacy highly relevant for integrated brain‑ and whole‑body aging strategies. Low magnesium status is consistently linked with insulin resistance, metabolic syndrome, hypertension, and low‑grade inflammation, all of which are major upstream drivers of both vascular cognitive impairment and Alzheimer‑type dementia. By improving insulin signalling, tempering oxidative stress and NF‑κB–mediated inflammation, and supporting endothelial function, magnesium can amplify the benefits of foundational lifestyle interventions such as Mediterranean‑style dietary patterns, regular physical activity, adequate sleep, stress reduction, and social engagement that have been associated with 10–30% lower risk of cognitive decline and dementia in longitudinal studies. In this systems perspective, magnesium sufficiency is best viewed as a synergistic co‑factor within a broader package that targets vascular risk, metabolic flexibility, and neuroinflammatory tone rather than as an isolated “magic bullet.” [13,15,66,67,68,69,70]

From a digital health and AI standpoint, emerging platforms enable far more granular identification and management of individuals at risk for suboptimal magnesium status as part of multimodal dementia‑prevention programs. Continuous and intermittent data streams, dietary logs, CGM traces, blood pressure and heart‑rate variability metrics, basic lab panels, and even polygenic or microbiome profiles can be ingested by machine-learning models to flag patterns suggestive of low magnesium intake or high magnesium demand (for example, insulin resistance, poorly controlled hypertension, high inflammatory burden) and to stratify patients into tailored neuronutrition pathways. Within these ecosystems, decision‑support tools can surface nudges toward magnesium‑rich foods, recommend appropriate laboratory or serum magnesium checks, and, where indicated, generate dose‑ and kidney‑function‑adjusted supplementation suggestions that are embedded alongside recommendations for Mediterranean‑style diets, exercise, sleep hygiene, and stress management. Such AI‑enabled personalization offers a scalable route to align magnesium optimization with an individual’s metabolic phenotype and evolving biomarker profile, operationalizing magnesium as one important node in an integrated, precision‑prevention framework for healthy cognitive aging [68,71,72,73,74].

Promising, Not Definitive: Gaps in the Magnesium Dementia Evidence Base

The current evidence base linking magnesium status with cognitive outcomes and dementia risk is constrained by several important methodological limitations that temper causal inference. Most available data derive from observational cohorts, which even with sophisticated adjustment remain vulnerable to residual confounding by overall diet quality, socioeconomic position, education, physical activity, comorbidities, and concomitant medications, as well as to reverse causality whereby early cognitive decline leads to dietary deterioration or supplement use changes. Cognitive endpoints are variably operationalized across studies, ranging from brief screening tools and domain‑specific neuropsychological tests to adjudicated mild cognitive impairment and clinical dementia diagnoses, while magnesium exposure is captured through diverse metrics (dietary recalls, supplements, serum, whole blood, or composite depletion scores), creating substantial heterogeneity that complicates meta‑analytic synthesis and translation into specific clinical thresholds. Randomized controlled trials, which are better suited to address causality, remain few in number, short in duration, and highly heterogeneous with respect to population selection, baseline magnesium status assessment, formulations and doses used, and the cognitive outcomes chosen, leading recent systematic reviews to conclude that trial data are insufficient to define optimal dosing, formulation, or target groups for dementia prevention. Consequently, longer‑term, adequately powered RCTs with standardized cognitive batteries and neuroimaging endpoints embedded within diverse population and incorporating repeated measures of magnesium intake and biomarkers are needed to determine whether correcting low magnesium or targeting higher‑normal ranges can meaningfully modify the incidence or progression of cognitive impairment and dementia [13,20,28,29,34,53.

Magnesium as a Cornerstone, Not a Silver Bullet, in Dementia Prevention

Accumulating observational and mechanistic evidence indicates that maintaining adequate, likely mid-range to moderately higher magnesium intake, primarily from whole foods, is consistently associated with larger brain volumes, fewer white‑matter lesions, and a lower risk of cognitive impairment and dementia across diverse cohorts. Neurobiological studies support a coherent mechanistic framework in which magnesium modulates NMDA receptor activity, stabilizes calcium homeostasis, attenuates neuroinflammation, improves metabolic and vascular function, and supports synaptic plasticity, while early randomized trials of oral magnesium (including brain‑penetrant formulations such as magnesium L‑threonate) show promising but still preliminary gains in cognitive performance and sleep‑related outcomes.

From a clinical and digital health perspective, these data justify a pragmatic focus on magnesium sufficiency within comprehensive brain‑health programs, particularly in mid‑life and in individuals with cardiometabolic risk factors or menopausal transition–related vulnerability.  Emphasizing magnesium‑rich dietary patterns (leafy greens, nuts, seeds, legumes, whole grains), systematic screening for subclinical deficiency or high magnesium depletion scores, and judicious supplementation tailored to kidney function, vitamin D status, and overall diet quality represents a low‑cost, biologically plausible strategy that can be integrated into multimodal dementia‑prevention and healthy‑aging frameworks. However, current evidence remains predominantly observational and heterogeneous, and high magnesium exposure appears to follow a U‑shaped association with dementia risk at the biomarker level, underscoring the need to position magnesium as one component of a broader lifestyle and risk‑factor portfolio, alongside blood pressure control, glycemic management, physical activity, sleep, hearing care, and social engagement, rather than as a stand-alone intervention, pending confirmation from large, long-term randomized trials with standardized cognitive and imaging endpoints.

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