Before i go into a laundry list of potential things I have found to enhance cognition, the very very first order of business is a good assessment of nutritional status (micro-nutrient panel), a good stool test, a good set of toxicity panels along with the metabolics associated with an organic acids test. If you don't have any B6, B2, B12, Choline, Carnitine, Serine, etc, well, you start there:). And if you still have significant deposits of mercury, cadmium, mycotoxins like ochratoxin A, Citrin, Zearalenone, and voc's like benzene, well, you have some foundational work to do first. And if you have overgrowths of pathogenic bacteria like Pseudonomas Argenosa, Klebsiella Pneumonia, or Citrobacter Freundii , Desulfovibro, or Clostridia, well, all these give off neuro toxic compounds, so first things first. And in case you are wondering, yes, i have 'walked all those back':). And to be complete if you are dealing with low blood oxygen, chronic platelet activation, blood glucose issues, and metabolic inflexibility, all those will compromise cognitive functioning too. And lastly, a good neuro transmitter panel can identify obvious deficits in acetylcholine, dopamine , serotonin and all the associated pre cursors. Now that, we have those things out of the way, we can get to all the cognitive enhancing supplements to consider and how they may interact with your genetics:).
Acetyl L Carnitine
- Research shows it helps protect the NMDA receptors from over activation, and helps us use and process fats for energy. However, chronic supplementation can lead to excitation of NFKB:). So perhaps we take breaks, and or consider our good friend resveratrol:).
- Acetyl L Carnitine and Pantethene even better. Pantethine has excellent benefits related to reducing cholesterol. 900mg of pantethene a day shows significant reductions in cholesterol in some clinical trials.
- ACAT Assist has both actyl l carnitine and pantethine.
Benfotiamine (B1) - AGE - Advanced Glycation End Products -
- Simply said, we dont like these, and Benfotiamine (fat soluable synthetic form of B1) is our friend here. Clinical trials for Alzheimers patients show significant cognitive performance improvement after 12 months with 300mg of benfotiamine a day.
- B1 also helps us utilize carbs for energy through the krebs cycle.
- Alpha GPC is one form of choline, and readily crosses the blood brain barrier.
- Some studies show significant cognitive improvement when Alpha GPC is combined with Piracteam, and which can help blood flow and transport choline.
- Alpha GPC is also neuro protective of the NMDA receptors from overstimulation
- Uridine is associated with cognitive improvement, and when combined with Alpha GPC and DHA, the results are even broader:).
- "These data suggest that administration of uridine for five consecutive days prevents REM sleep deprivation-induced deficits in learning and memory associated with enhanced tCaMKII and pCREB ratios in the hippocampus"
- Lots of good research on this one, both with cognitive improvement in alzheimers and stroke patients, as well as a reduction in mitochondrial oxidative stress. There that word is again:)
"Citicoline (1,000 mg/day) improves cognitive performance in Alzheimer's patients
Examinations were done at baseline (T0) and after the 12 weeks of treatment (T12). As compared to placebo, citicoline improved cognitive performance in Alzheimer's disease patients with APOE E4 (ADAS: difference between groups = -3.2 +/- 1.8 scores, p < 0.05; ADAS-cog: difference between groups = -2.3 +/- 1.5, ns); and this improvement on cognition was more pronounced (ADAS, p < 0.01; ADAS-cog: difference between groups = -2.8 +/- 1.3, p < 0.06) in patients with mild dementia (GDS < 5). Citicoline also increased cerebral blood flow velocities in comparison with placebo (p < 0.05) when transcranial Doppler recordings from both hemispheres were considered together, as well as diastolic velocity in the left middle cerebral artery (p < 0.05). Patients treated with citicoline showed an increase in the percentage of brain bioelectrical activity of alpha (occipital electrodes) and theta type (left side electrodes), accompanied by a decrease in relative delta activity particularly marked in the left temporal lobe.
Benefits of CDP Choline 
1) Used for the treatment of neurodegenerative disorders associated with head trauma, stroke, brain aging, cerebrovascular apthology and Alzheimer's disease.
2) Double blind placebo controlled study in Alzheimer's disease patients indicates that CDP Choline (1,000mg/day) is well tolerated and improves cognitive performance, cerebral perfusion, and the brain bio electric patterns.
Even more effective in those with the e4 APOE genotype.
Some of the benefits of CDP Choline on brain function:
Activates the biosynthesis of phospholipids in neuronal membranes
Increases brain metabolism
Increases norepinephrine and dopamine levels in the central nervous system
Neuroprotective effects during hypoxia and ischemia
Improves learning and cognitive performance in animals
Protects ATPase activity of mitochondrial and membrane Na+/K+ ATPase
Inhibits Phospholipase A2
Reverses cerebral edema in various experimental models
Use for healthy people to increase focus
CDP Choline markedly improved reduction in stroke impairment across 197 patients 
Clearly elevated PLA2 level for MS patients, and markedly different levels of PLA2 of mild vs severe MS patients. 
Clearly elevated PLA2 activity for Autism patients, with data almost completely non overlapping compared to controls. 
Carnosine was proposed as an anti-aging agent more than 20 years ago. During the following years, several human studies have been carried out to test its possible positive effects in the elderly. It has been shown that dietary supplementation of carnosine (250–350 mg/daily) in combination with its methylated analogue anserine (β-alanyl-1-N-methyl-L-histidine) (650–750 mg/daily) for about 13 weeks is able to improve cognitive function and physical activity , to preserve verbal episodic memory and brain perfusion , and to modulate network connectivity changes associated with cognitive function in elderly people. However, Carnosine also impacts copper transport, so those of you who struggle with copper sufficiency may want to look elsewhere.
- Spearmint shows significant cognitive performance improvement, and the mechanism of action appears multi fold. Reduction in oxidative stress (high concentrations of rosmaric acid) and it inhibits the enzyme that breaks down choline:).
"Quality of working memory and spatial working memory accuracy improved after supplementation
with 900 mg/day spearmint extract by 15% , respectively, versus placebo. Subjects consuming 900 mg/day spearmint extract reported improvement in their ability to fall asleep, relative to subjects consuming placebo. Overall treatment effects were evident for vigor-activity, total mood disturbance, and alertness and behavior following wakefulness, with trends observed for improvements after spearmint supplementation relative to placebo. Conclusions: These results suggest that the distinct spearmint extract may be a beneficial nutritional intervention for cognitive health in older subjects with AAMI (Age Associated Memory Impairment)."
Silk (silk fibroin enzyme hydrolysates (FEH))
- Shows significant cognitive performance improvement related to memory.
- "...it can be concluded that silk FEH exhibit beneficial cognitive effects with respect to memory and learning, attention, mental focus, accuracy, memory recall, and overall memory and concentration. These conclusions are supported by studies in rats and mice. Mechanistic studies that have been conducted in animals and cell culture systems are also reviewed. These studies indicate that silk FEH exerts its positive effects on memory and learning by providing neuroprotection via a complex mechanism involving its potent antioxidant and inflammation-inhibiting activities. Acetylcholine (ACh) is secreted by cholinergic neurons, and plays a role in encoding new information. Silk FEH were shown to decrease the levels of the pro-oxidant and pro-inflammatory mediators interlukin-1 (IL-1), IL-6 and tumor necrosis factor-alpha (TNF-), protecting the cholinergic system from oxidative stress, thus enhancing ACh levels in the brain, which is known to promote cognitive functions. In addition, the expression of brain-derived neurotrophic factor (BNDF), which is involved in the survival of neurons, is enhanced, and an increase in the expression of the phosphorylated cAMP response element-binding protein (p-CREB) occurs, which is known to play a positive role in cognitive functions. No adverse effects have been reported in association with the use of silk FEH."
Phosphatydil Serine (Seriphos)
- This is a favorite of people that help folks recover from brain injuries.
- Is it a coincidence that there is a transporter that takes Phosphatdyl Serine into the inner membrane of the mitochondria where cardio lipin live ? Hmm, not likely.
- Is it a coincidence that people who live in areas of Japan that have high levels of Serine in their diets live much longer ? L-Serine is a pre cursor to Phosphaydil Serine:). See my blog article on thyroid health if you dont think L-Serine levels are essential:).
"No treatment strategy is available that has been shown to increase the number of synapses in
brains of Alzheimer patients or, for that matter, of normal people. The agents now available
for treating Alzheimer’s disease act by amplifying (acetylcholinesterase inhibitors) or
modulating (glutamate antagonists) the actions of particular neurotransmitters. These drugs
have only small and transient therapeutic effects, and apparently do nothing either to slow
synaptic loss or to accelerate the production of new synapses that might compensate for this
loss. The loss is generally thought to result from the locally-toxic effects of an endogenous
peptide, A-beta, or its aggregates3–4 on synapses themselves or on their anatomic precursor,
dendritic spines......New studies have shown that treating animals concurrently with three particular phosphatide precursors present in the blood and formed endogeneously (uridine and choline) or derived from foods (choline and omega-3 fatty acids) can have both of these effects: It increases brain
phosphatides, synaptic proteins, neurite outgrowth and the formation of dendritic spines5.
This treatment also enhances cognition and the release of some brain neurotransmitters in
the animals. Moreover, administration of the phosphatide precursors (along with additional
supporting nutrients) to patients with mild Alzheimer’s disease significantly improved
cognition in an initial large-scale (212 patients) clinical trial, discussed below."
"In summary, 14-day administration of GBE was associated with a modest improvement in accuracy in an object WM task and evidence of increased synaptic inhibition at left temporal and prefrontal sites during the hold component of the WM task. We suggest that the improvements in WM task performance are a consequence of enhanced synaptic inhibition associated with GBE, possibly operating via a cholinergic mechanism. These findings provide further evidence for the efficacy of GBE as a treatment for working memory deficits in the elderly."
Huperzine A is extracted from Chinese herb named Huperzia serrate which is commonly known as club moss and has been used for centuries to treat the inflammation, swelling, strains and fever 35. It also potentially improves the cognitive function by increasing ACh levels in the brain 59 due to an efficacy to act as a natural inhibitor of AChE 181. Its neuro-protective mechanism of action is similar to donepezil and galantamine 182 but it parades effective penetration to the BBB, higher oral bioavailability as well as longer duration of action 59. Different strategies have been done to develop the alternative sources of huperzine A because it occurs in slow growing members of Huperziaceae. This includes Phlegmariurus aquarrosus in vitro tissue culture 183 and extraction from endophytic fungi which is secluded from huperzine A manufacturing herb 184,185.
16.1 Therapeutic efficacy of huperzine A in AD Huperzine A ameliorates the pathogenesis of AD through its neuro-protective property which majorly involves the mitochondrial protection from Aβ aggregation induced toxicity. In vitro as well as in vivo studies revealed that it acts as an inhibitor of Aβ and thus protects the mitochondrial damage to attenuate the oxidative stress 33. The chronology of Aβ induced neuron functional impairment is not utterly understood. However, a number of indications propose that Aβ causes extra-synaptic space glutamate level elevation that consequences in ligand gated excitatory ion channels NMDARs overstimulation and finally leading to cell death as well as synaptic loss 186,187. Huperzine A reduces the glutamate excite-toxicity via acting as NMDA receptor antagonist and minimize the level of synaptic loss along with neuronal cell death 188. As the brain derived neurotropic factor (BDNF) is crucially important in memory and learning process, because it regulates synaptic plasticity, neuronal differentiation, axonal sprouting, as well as long-term potentiation (LTP) 189. It has been revealed by voluminous number of studies that there is a reduced or diminished level of BDNF in patients with AD as well as with mild cognitive impairment (MCI) 189. Huperzine A potentially exerts neuroprotection activity via signaling and promoting the production of BDNF and pro- BDNF to minimize the cognitive deficits and learning impairment induced by reduced level of BDNF 190.Due to the potential neuroprotection possessions of huperzine A there is a need of further research to consider it as a drug for the treatment of AD.
Toxicity of Huperzine A Although huperzine A has been stated as a potential fighter of cognitive decline but it could be a lethal agent at high dose. Studies clarified its lethal dose as >4mg/kg of bodyweight and even 3mg/kg for longer period like180 days in male rats whereas 1mg/kg dose has been postulated as lethal for female rats as 2-4mg/kg of bodyweight.
Cognitive decline is believed to be associated with neurodegenerative processes involving excitotoxicity, oxidative damage, inflammation, and microvascular and blood-brain barrier dysfunction. Interestingly, research evidence suggests upregulated synthesis of lipid signaling molecules as an endogenous attempt to contrast such neurodegeneration-related pathophysiological mechanisms, restore homeostatic balance, and prevent further damage. Among these naturally occurring molecules, palmitoylethanolamide (PEA) has been independently associated with neuroprotective and anti-inflammatory properties, raising interest into the possibility that its supplementation might represent a novel therapeutic approach in supporting the body-own regulation of many pathophysiological processes potentially contributing to neurocognitive disorders. Here, we systematically reviewed all human and animal studies examining PEA and its biobehavioral correlates in neurocognitive disorders, finding 33 eligible outputs. Studies conducted in animal models of neurodegeneration indicate that PEA improves neurobehavioral functions, including memory and learning, by reducing oxidative stress and pro-inflammatory and astrocyte marker expression as well as rebalancing glutamatergic transmission. PEA was found to promote neurogenesis, especially in the hippocampus, neuronal viability and survival, and microtubule-associated protein 2 and brain-derived neurotrophic factor expression, while inhibiting mast cell infiltration/degranulation and astrocyte activation. It also demonstrated to mitigate β-amyloid-induced astrogliosis, by modulating lipid peroxidation, protein nytrosylation, inducible nitric oxide synthase induction, reactive oxygen species production, caspase3 activation, amyloidogenesis, and tau protein hyperphosphorylation. Such effects were related to PEA ability to indirectly activate cannabinoid receptors and modulate proliferator-activated receptor-α (PPAR-α) activity. Importantly, preclinical evidence suggests that PEA may act as a disease-modifying-drug in the early stage of a neurocognitive disorder, while its protective effect in the frank disorder may be less relevant. Limited human research suggests that PEA supplementation reduces fatigue and cognitive impairment, the latter being also meta-analytically confirmed in 3 eligible studies. PEA improved global executive function, working memory, language deficits, daily living activities, possibly by modulating cortical oscillatory activity and GABAergic transmission. There is currently no established cure for neurocognitive disorders but only treatments to temporarily reduce symptom severity. In the search for compounds able to protect against the pathophysiological mechanisms leading to neurocognitive disorders, PEA may represent a valid therapeutic option to prevent neurodegeneration and support endogenous repair processes against disease progression."
Oxidative Stress Reduction And Cognitive Performance Improvement
"Cognitive impairment reduces quality of life and is related to vascular and neurodegenerative disorders. However, there is also a close relationship between these diseases and oxidative stress. Thus, the purpose of this study was to assess whether inflammation and oxidative damage are associated with low cognitive performance in the elderly with different housing conditions. Methods. The study groups consisted of 32 institutionalized and 25 noninstitutionalized Brazilian elderly subjects. Oxidative damage, inflammation markers, and cognitive function were evaluated. Results. The results demonstrated pronounced oxidative stress in the institutionalized elderly group, which also had a lower antioxidant status compared to noninstitutionalized subjects. High levels of proinflammatory cytokines were also observed in the institutionalized elderly. Furthermore, the raised levels of inflammatory markers were correlated with increased oxidative stress, and both were associated with low cognitive performance. However, based on multiple linear regression analysis, oxidative stress appears to be the main factor responsible for the cognitive decline. Conclusions. The findings suggest that individuals with lower antioxidant status are more vulnerable to oxidative stress, which is associated with cognitive function, leading to reduced life quality and expectancy."
A pattern i consistently see in people who struggle cogntively, is excessive mitochondrial oxidative stress. There are a series of pathways involved here in both the over production of free radicals and genetic pathways for the systems designed to neutralize this oxidative stress. They can be found in other blog articles.
Lions Mane - Last but not least
This mushroom has been growing in popularity, and rightfully so. It has quite impressive neuro and cognitive enhancing properties, HOWEVER, be careful if NMDA receptor issues are in play - all nightshades have a compound that can irritate them. 
Neuro transmitter support - directly for dopamine
I hesitate to list this - because its really just supportiev of healthy neuro transmitter levels, but things like Bacopa, Macuna, Tyrosine, Gota Kola, BH4 (royal jelly) all have a role to play in maintaing the appropriate amount of dopamine - which is key in cognitive performance.
Therapeutic effect of palmitoylethanolamide in cognitive decline: A systematic review and preliminary meta-analysis of preclinical and clinical evidence. Marco Colizzi, Riccardo Bortoletto,. Front Psychiatry. 2022; 13: 1038122.
Improvement of cognitive functions by oral intake of Hericium erinaceus