The search for effective interventions to prevent, delay, or ameliorate cognitive decline is of paramount importance, especially given the complex mechanisms underlying age-related cognitive decline and dementia
[20]. These mechanisms encompass a spectrum of pathologies, ranging from microvascular issues
[21], including blood–brain barrier (BBB) disruption
[22][23][24][25], impaired cerebral blood flow regulation
[26][27][28][29], impaired glymphatic function
[30], and small vessel disease
[31][32] to macrovascular pathologies such as atherosclerosis
[33] and stroke. Additionally, neuroinflammation
[34][35], synapse loss, white matter damage
[36][37] and changes in connectivity
[38][39], neuronal metabolic dysfunction
[40][41] and amyloid pathologies
[42][43] play significant roles in the progression of cognitive impairment and dementia. These multifaceted and interrelated pathologies highlight the complexity of brain aging and the challenges in mitigating cognitive decline. While pharmacological treatments have shown some benefits, they may not fully address the multifaceted nature of cognitive decline
[44][45][46]. This has led to growing interest in alternative approaches
[47][48][49][50], particularly dietary interventions and nutritional supplementation
[51][52][53][54], as a potential means to support cognitive health. Nutrition plays a crucial role in brain health, and deficiencies in specific nutrients have been linked to cognitive impairments
[55][56][57].
2. Vitamin B
B vitamins play a crucial role in maintaining cognitive function during aging, acting as essential cofactors in various neurological processes
[73]. As individuals age, the risk of B vitamin deficiencies increases, potentially leading to cognitive decline
[74]. Vitamins B6, B9 (folate), and B12 are particularly important, as they contribute to the maintenance of normal brain function by influencing homocysteine metabolism, an amino acid linked to neurodegenerative diseases and cardiovascular and cerebrovascular impairment when present at elevated levels
[75][76]. Studies
[77][78][79] have demonstrated that a high intake of these B vitamins can significantly slow cognitive decline in older adults, particularly in those with elevated homocysteine levels or mild cognitive impairment
[74][80]. For instance, supplementation with B vitamins has been shown to lower homocysteine levels, thereby reducing the rate of brain atrophy and improving cognitive outcomes
[81]. Additionally, B vitamins are involved in the synthesis of neurotransmitters and the maintenance of myelin, the protective sheath around nerve fibers, which is crucial for efficient brain signaling
[81]. This protective effect of B vitamins against cognitive decline is especially beneficial for older adults who are at an increased risk of dementia, suggesting that adequate intake of these nutrients could play a key role in preserving cognitive health in the aging population
[73][74][77][78][80].
3. Vitamin C, Vitamin E and Other Antioxidants
Supplementation with vitamin C, vitamin E, and other antioxidants plays a potential important role in preserving cognitive function during aging, primarily through their ability to combat oxidative stress
[82], a key factor in cellular aging
[83] and the development of cardiovascular
[84] and cerebrovascular impairment
[85], neurodegeneration
[86] and age-related cognitive decline
[87].
Vitamin C is a potent antioxidant that can help protect the brain from oxidative stress, which can impair cognitive functions
[88]. In addition, vitamin C plays a pivotal role in the synthesis and functioning of the neurotransmitters dopamine and noradrenaline found in the brain
[88]. Several studies have explored the associations between vitamin C and physical and mental well-being; its deficiencies may increase the risk of severe conditions such as cancer, heart disease, and diabetes
[89][90][91]. Research has also found links between vitamin C deficiency and attention, concentration, executive function, memory, linguistic and conceptual thinking
[92][93][94]. Low levels of vitamin C can negatively affect mood, potentially leading to depression and cognitive impairment
[95], in other words, higher levels of vitamin C are correlated with improved mood and reduced depression and confusion
[92]. A meta-analysis has described how vitamin C supplementation can enhance the mood in individuals with depression
[96]. Consequently, this can improve cognitive performance and reduce the “brain fog” associated with depression
[96]. Further research and long-term follow-up studies involving more patients are needed to establish the preventive effect of vitamin C against the development and progression of Alzheimer’s disease
[97]. In conclusion, there existing evidence suggests that maintaining healthy levels of vitamin C may be protective against age-related cognitive decline and neurodegenerative diseases, and that cognitive function improves with vitamin C supplementation
[97][98].
Vitamin E is a potent fat-soluble antioxidant. It interacts and synergizes with several other antioxidants, such as glutathione, selenium, vitamin C, carotenes, and carotenoids
[99]. Vitamin E protects brain cells from oxidative stress-induced damage
[100] and is particularly effective in maintaining neuronal integrity and function. It is known for its protective effects against lipid peroxidation in cell membranes, which is vital for preserving cognitive health. Studies have shown that individuals with a higher intake or serum levels of these antioxidants have a lower risk of cognitive decline and dementia, including Alzheimer’s disease
[99][100][101]. The existing evidence supports the inclusion of vitamin E supplementation in a dietary protocol aimed at preserving cognitive health in the elderly.
Polyphenols, including resveratrol and curcumin, represent a diverse group of compounds with potent antioxidant and anti-inflammatory properties, playing a significant role in the preservation of cognitive function in aging. Resveratrol, found in grapes and red wine, has gained attention for its potential neuroprotective effects. It is believed to activate pathways that help in protecting cells from damage and improve blood flow to the brain, thereby potentially enhancing cognitive functions and reducing the risk of neurodegenerative diseases
[102]. Clinical evidence suggests that resveratrol supplementation can improve memory and cognitive performance in older adults
[102][103].
Curcumin, the active component of turmeric, is another widely studied polyphenol known for its strong anti-inflammatory and antioxidant properties. It has been shown to cross the blood–brain barrier and exert neuroprotective effects, potentially helping in the prevention of age-related cognitive decline. Studies indicate that curcumin may improve memory and mood in people with mild, age-related memory loss
[104][105].
Other polyphenols, like flavonoids, found in berries, tea, and cocoa, are also crucial for cognitive health
[106][107]. Flavonoids have been associated with improved cognitive abilities, reduced risk of dementia, and enhanced memory and learning in older adults
[108]. For example, epigallocatechin gallate (EGCG) from green tea has been studied for its role in protecting neurons, reducing the formation of amyloid plaques, and improving cognitive function
[109].
Another class of polyphenols, anthocyanins, found in dark-colored fruits like blueberries, have been shown to improve neural signaling and enhance memory
[110]. Regular consumption or supplementation with these polyphenols can provide antioxidative and anti-inflammatory benefits, which are particularly beneficial in countering age-related cognitive decline
[103]. However, while the biological effects of these compounds are well-documented, more large-scale, long-term clinical trials are needed to conclusively establish their efficacy in preventing or slowing down cognitive impairment in older adults.
4. Vitamin D
Vitamin D, essential for overall health, plays a multifaceted role ranging from maintaining bone health to supporting immune system functions
[111][112]. It aids in the absorption of calcium and phosphorus, crucial for optimal bone density, and is involved in normal muscle function and blood sugar metabolism
[113][114]. Its significance extends to the development of the brain and nervous system in early childhood and is crucial for cognitive functions such as memory, thinking, and concentration in later life
[115]. Vitamin D is also instrumental in producing neurotransmitters like dopamine and serotonin, which regulate mood and emotions
[115].
Approximately 40% of the European population is affected by vitamin D deficiency, which can worsen during the late winter months
[116]. Consequently, the recommended daily intake for adults has been increased to 2000 IU/day
[116][117]. The elderly, along with individuals with chronic diseases, specific dietary preferences, or certain health conditions, are particularly vulnerable to this deficiency
[118][119]. Notably, vitamin D deficiency is linked to an increased risk of diseases like type 2 diabetes, cancer, multiple sclerosis, depression, Parkinson’s, and Alzheimer’s disease
[120][121]. A study
[122] involving over 1600 elderly individuals revealed that those with mild vitamin D deficiency were over 50% more likely to develop dementia, and the risk was even higher in those with severely low levels. These findings underscore the importance of maintaining adequate vitamin D levels for cognitive health.
Clinical evidence supports the role of vitamin D supplementation in preserving cognitive function, especially in older adults
[123][124][125]. Research has shown that adequate levels of vitamin D are associated with improved cognitive performance, and supplementation has been found to benefit those with deficiencies
[123][124][125]. This is particularly crucial for cerebrovascular health, as vitamin D supports blood flow to the brain and reduces the risk of cerebrovascular diseases, which can impact cognitive abilities
[120][121]. Its role in neuroprotection, neurotransmission, and brain plasticity highlights its potential as a key nutrient in maintaining brain health during aging
[126][127]. Therefore, vitamin D supplementation could be a strategic approach in mitigating the risk of age-related cognitive impairment and supporting overall brain health in the elderly population. The exact mechanisms are thought to involve vitamin D’s role in neuroprotection, neurotransmission, and brain plasticity, highlighting its potential as a crucial nutrient in maintaining brain health with aging. However, while these associations are promising, further large-scale, long-term studies are needed to establish definitive causal links between vitamin D supplementation and cognitive function preservation in older adults
[126][127].
5. Vitamin K
In the human body, vitamin K is an essential component for physiological processes and is also a fat-soluble vitamin
[128]. It is naturally expressed in two forms, namely K1 (phylloquinone) and K2 (menaquinone), both of which play pivotal roles in a wide spectrum of physiological processes
[128]. Its principal function is to modulate hemostasis through the synthesis of coagulation factors. In addition to these primary roles, vitamin K is also required for various functions in cell growth, proliferation, cell genesis, and apoptosis
[128][129][130]. Maintenance of normal vitamin K levels may also contribute to the preservation of memory in the elderly
[130]. There are studies suggesting a link between reduced serum concentrations of vitamin K and deterioration of cognitive function in the geriatric population (aged 65 years and above)
[130][131][132]. Preclinical studies raise the possibility that vitamin K2 may protect nerve cells against the toxicity of amyloid β
[133].
6. Omega-3 Polyunsaturated Fatty Acids
Omega-3 polyunsaturated fatty acids (PUFAs)
[56][111] are increasingly recognized for their critical role in maintaining cognitive function during aging, with ongoing research continuously examining their positive effects on central nervous system functions, including memory, attention, concentration, learning capabilities, and overall well-being
[52][65][134][135][136][137]. These fatty acids, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are crucial components of cell membranes in the brain and are involved in various neurophysiological processes
[52][64][134][136][138][139][140][141]. DHA, the most abundant omega-3 fatty acid in the brain, is vital for the maintenance and function of neural cells
[65][135][136][137]. It is known for its role in enhancing synaptic plasticity and neuronal signaling, which are key factors in cognitive processes like learning and memory
[139]. EPA, on the other hand, contributes to cognitive health primarily through its anti-inflammatory properties, which are beneficial in reducing neuroinflammation, a contributing factor to cognitive decline and the development of neurodegenerative diseases
[52][64][134][136][138][139][140][141][142][143]. Higher doses of omega-3, typically ranging from 500 to 2000 mg per day, have been suggested to alleviate symptoms of depression and anxiety, further supporting cognitive health
[144]. The Western diet, unfortunately, tends to contain more omega-6 fatty acids compared to omega-3, which can be detrimental to health
[145]. The optimal ratio of omega-6 to omega-3 is closer to 2:1, and since the body cannot produce these fatty acids, they must be obtained through diet or supplements, with effective doses for various health conditions ranging from 250 to 4000 mg of omega-3 per day
[145][146]. Sources of omega-3 include fatty fish like salmon, mackerel, tuna, and plant sources such as flaxseed, chia seeds, nuts, and canola oil
[52][64].
Regular consumption of omega-3 supplements is beneficial for cognitive and emotional development, reading skills, and cognitive and concentration abilities
[52][65][134][135][136][137]. Furthermore, omega-3 PUFAs have shown potential in reducing the risk of neurodegenerative diseases like Alzheimer’s disease
[147], potentially slowing the progression of the disease, delaying its onset, and being associated with improved cognitive abilities. Clinical studies have also demonstrated that regular intake of omega-3 fatty acids can alleviate symptoms of mental health disorders such as depression
[134][148][149]. DHA is also essential for the retina, with deficiency leading to vision problems and increased risk of eye diseases
[150]. Additionally, omega-3 fatty acids positively affect bones, muscles, and joints, enhancing bone strength and reducing the risk of osteoporosis
[151][152]. Therefore, consistent use of omega-3 supplements has been associated with multifaceted health benefits, including improved cognitive ability and reduced susceptibility to cognitive decline
[52][64][134][136][138][139][140][141].
7. Mineral Supplementation
Mineral supplementation plays a critical role in supporting brain and cognitive health, particularly in the aging population
[153][154]. Minerals, being inorganic substances essential for the body’s physiological functions, cannot be synthesized endogenously and must be obtained through diet or supplementation. Their impact on cognitive abilities is increasingly recognized
[153][154].
Magnesium supplementation, for instance, is associated with enhanced cognitive functions and a reduced risk of dementia
[155]. Studies
[155][156] have demonstrated that individuals with higher magnesium levels have a notably lower risk of dementia. Increased magnesium intake is particularly beneficial for brain health and may help in preserving intellectual function and reducing the risk of dementia, as it protects nerve cells and positively influences blood pressure.
Iron is vital for numerous physiological processes, including cognitive function and cellular metabolism
[157][158][159][160][161][162]. Even mild forms of iron deficiency can impair concentration and reduce immunity, and are linked with delayed neurological development and poorer academic performance. Iron supplementation has been shown to positively affect intelligence quotient (IQ) scores and iron-deficiency anemia in the elderly is associated with an increased prevalence of dementia and Alzheimer’s disease
[157][158][159][160][161][162].
Selenium is a crucial component of antioxidant enzymes like glutathione peroxidase
[163]. These enzymes protect the brain from oxidative stress, which is implicated in aging and neurodegenerative diseases like Alzheimer’s and Parkinson’s
[163]. Oxidative stress damages brain cells and impairs cognitive function, so selenium’s role in combating this stress is vital for maintaining cognitive health
[87][164][165][166][167][168]. Selenium, contributing to antioxidant defenses, can reduce the risk of diseases by boosting immune function. It has been found that higher levels of selenium in the blood are associated with a reduced risk of cognitive decline and certain types of cancer
[169][170]. Selenium is also crucial for the proper functioning of the thyroid gland and plays a vital role in immune health.
Zinc, essential for growth, development, and immune system function
[171], is beneficial for the nervous system and may help prevent depression due to its tranquilizing properties. However, zinc deficiency can lead to a decline in cognitive functions and memory
[172][173]. Zinc is also vital for the functionality of the antioxidant enzyme superoxide dismutase, which helps eliminate free radicals
[174][175][176].
Copper, involved in energy production, connective tissue formation, and the integrity of the cardiovascular and immune systems, requires a balanced intake with zinc
[177]. Copper is found in diverse food sources and is also available as a dietary supplement. While copper performs many vital biological functions, the relationship between its intake and the development of diseases like Alzheimer’s disease remains complex, with research suggesting that both excess and deficiency may have adverse consequences
[178][179].
In summary, minerals such as magnesium, iron, selenium, zinc, and copper are integral to maintaining cognitive health, particularly in the aging population. Their supplementation can support various brain functions, from cognitive performance to reducing the risk of neurodegenerative diseases. This highlights the importance of ensuring adequate mineral intake, either through diet or supplementation, as part of a strategy to preserve cognitive function and overall brain health in older adults.