Does it make your memory better?

What this archive is for. Trials of the compound come first, ranked by how many people were actually given it. Studies that only observed people are below them and labelled.

1. 01SemaglutidePeptideStrong. At least two finished studies in people, and at least 1,000 people who took it. 12 completed trials, 42,363 people given it.10 reported

   3,808 people given it1 trial

   • Semaglutide was tested properly in Alzheimer's disease and it did not work. Nearly four thousand people whose early Alzheimer's had been confirmed by an amyloid test took a daily semaglutide pill or a dummy pill for two years. Nobody involved knew which. Memory and daily function slipped at the same rate in both groups. Both trials were stopped and written up as negative. A test this large would have found a real benefit if there was one.

     The numbers 3,808 participants with amyloid-confirmed early Alzheimer's disease across 566 sites: oral semaglutide did not slow decline on the CDR-SB primary endpoint at week 104 and both trials were discontinued for negative clinical outcome.

     The Lancet, 2026· 3,808 people

   What people using it report

   • The effect people describe valuing most is appetite and food preoccupation falling away rather than the number on the scale, and it is frequently described in terms of no longer having to spend attention on food.
2. 02CerebrolysinPeptideStrong. At least two finished studies in people, and at least 1,000 people who took it. 3 completed trials, 1,591 people given it.8 reported

   521 people given it2 trials

   • The lowest dose helped thinking and the higher doses did not, which is hard to explain. 279 patients with mild to moderate Alzheimer's got one of three doses or a dummy drip for 24 weeks, and nobody involved knew which. Only the smallest dose improved scores on the standard cognition test. The two larger doses did nothing. The authors call this an upside-down dose curve. A real drug usually does more as the dose rises, not less.

     The numbers 279 patients randomized to 10, 30 or 60 mL or placebo: only the 10 mL dose improved cognition on ADAS-cog (P=0.038), with the two higher doses failing to do so. The authors describe an inverted U-shaped dose response.

     European Journal of Neurology, 2006· 279 people

   • Cerebrolysin improved thinking scores in vascular dementia, on evidence later graded very weak. 242 patients took it as a drip on top of aspirin for 24 weeks, and nobody involved knew who got the real thing. Scores on the standard cognition test improved by 10.6 points against 4.4 on the dummy. A doctor's overall impression of the patient also favoured the drug. Cochrane later rated this whole body of work very low quality, and the manufacturer supported the trials.

     The numbers 242 patients over 24 weeks as add-on to aspirin: ADAS-cog+ improved 10.6 points versus 4.4 on placebo (least squares mean difference -6.17) and CIBIC+ by 0.84 points. Cochrane later graded this body of evidence very low quality.

     Journal of Stroke and Cerebrovascular Diseases, 2011· 242 people

   What people using it report

   • What people describe wanting from it is mood, cognition and easier opioid withdrawal, with effects said to appear within a small number of injections. Those are individual accounts, not a pattern across many posters.
3. 03OxytocinPeptideModerate. At least one finished study in people, and at least 100 people who took it. 2 completed trials, 290 people given it.5 reported

   290 people given it1 trial1 found nothing

   • found nothingOxytocin nasal spray was tested properly in autism and it did not work. Two hundred and ninety children and teenagers used the spray or a dummy every day for about six months, and nobody involved knew which. Social withdrawal, the thing the trial was built to move, was no better on oxytocin. Nothing else measured came out differently either. A trial this size would have found a worthwhile benefit if there was one. This is the strongest test the idea has had.

     The numbers 24-week Phase 2 RCT in 290 children: no significant difference from placebo on social withdrawal (least-squares mean difference minus 0.2) or secondary social and cognitive measures.

     New England Journal of Medicine, 2021· 290 people

4. 04TesamorelinPeptideStrong. At least two finished studies in people, and at least 1,000 people who took it. 8 completed trials, 1,729 people given it.10 reported

   152 people given it1 trial

   • Thinking scores edged up, and this was one modest trial. 152 adults aged 55 to 87 took tesamorelin or a dummy injection daily for about five months. Sixty six of them already had mild memory problems. The drug group did a little better at tests of planning and mental flexibility, by enough to separate from chance. IGF-1 more than doubled but stayed inside the normal range. No other team has repeated this, it ran only five months, and it did not test whether anyone's memory loss progressed.

     The numbers 152 adults aged 55 to 87 (66 with MCI): 20 weeks of tesamorelin 1 mg daily had a favorable effect on cognition (P=.03), mainly executive function, and raised IGF-1 117% within the physiological range.

     Archives of Neurology, 2012· 152 people

5. 05Tesamorelin / IpamorelinBlendStrong. At least two finished studies in people, and at least 1,000 people who took it. 5 completed trials, 1,507 people given it.9 reported

   152 people given it1 trial

   • A low dose of tesamorelin nudged thinking in the right direction in older adults. A hundred and fifty two people aged 55 to 87 took it or a dummy shot for five months, and sixty six of them already had mild memory trouble. The gain showed up mainly in planning and mental flexibility. IGF-1 more than doubled while staying inside the normal range. The dose was 1 mg, half the dose used for belly fat, and this trial did not measure fat at all.

     The numbers 152 adults aged 55 to 87, of whom 66 had mild cognitive impairment. Twenty weeks of tesamorelin at 1 mg daily had a favourable effect on cognition, P equal to 0.03, concentrated in executive function, and raised IGF-1 by 117 percent within the physiological range. Note the dose: 1 mg, which is half the dose that produced the visceral fat result, and this trial did not measure visceral fat.

     Archives of Neurology, 2012· 152 people

6. 06NAD+ / B ComplexBlendLimited. People have taken it in a published study, but fewer than 100 of them. 5 completed trials, 34 people given it.8 reported

   0 people given it2 trials2 found nothing

   • found nothingThe blood test improved and the person did not. Two hundred and seventy one older people with diabetes and borderline low B12 took a high dose of it, or a dummy, for over two years. Two blood markers of B12 shortage dropped, exactly as they should. Thinking and memory declined at the same rate in both groups. This is the whole trap with B12. The number on the report moves and nothing you would notice moves with it.

     The numbers 271 diabetic outpatients aged 70 or over with plasma B12 between 150 and 300 pmol per litre took methylcobalamin at 1,000 micrograms daily or placebo for 27 months. Serum methylmalonic acid and homocysteine fell significantly against placebo at months 9 and 27. There was no significant difference in cognitive decline at month 27. The blood marker moved and the outcome did not.

     Clinical Nutrition, 2017· number of people not given

   • found nothingThe same lesson again, in people already losing their memory. Two hundred and seventy nine older adults with mild memory trouble took B12 with folic acid, or a dummy, for two years. Homocysteine, the blood marker the whole theory hangs on, fell by about a third. Their decline in thinking was no slower than the dummy group's. Fixing the marker protected nobody. Two trials now say the same thing, which makes it hard to put down to bad luck.

     The numbers 279 outpatients aged 65 or over with mild cognitive impairment and raised homocysteine took methylcobalamin at 500 micrograms plus folic acid, or placebo, for 24 months. Homocysteine fell from 13.9 to 9.3 micromoles per litre. There was no significant difference in cognitive decline at 24 months. A second worked example of the same lesson.

     Clinical Nutrition, 2020· number of people not given

7. 07Kisspeptin-54PeptideModerate. At least one finished study in people, and at least 100 people who took it. 5 completed trials, 122 people given it.8 reported

   0 people given it1 trial

   • A nasal spray version works, at least on hormones. In a controlled study, kisspeptin sprayed up the nose quickly raised the hormones that drive the ovaries and testes. That matters, because it shows an injection is not the only way in. Note what was measured. A hormone level in the blood. Nothing about how anyone felt, thought or performed was tested here.

     The numbers A randomised controlled study extending the route: intranasal kisspeptin rapidly stimulated gonadotropin release in humans. Relevant because it establishes that a non-injected route works, and it still measures gonadotropins rather than any behavioural or cognitive outcome.

     EBioMedicine, 2025· number of people not given

8. 08DavunetidePeptideModerate. At least one finished study in people, and at least 100 people who took it. 1 completed trial, 313 people given it.2 reported

   nobody was given it1 watch-only study1 found nothing

   • found nothingPeople with schizophrenia took it safely, and their thinking did not improve. A standard battery of tests measured memory, attention and problem solving, and the drug made no difference on any of it. A second measure, of how well people handled everyday tasks in a role play, leaned slightly the drug's way. That was not the question the trial was built to answer, and one leaning measure is not a result. Read this as a miss with a loose end.

     The numbers Well tolerated; no significant effect on MCCB cognition, with a modest signal on functional capacity (UPSA).

     Schizophrenia Research, 2012· number of people not givenobserved only, nobody was given it

9. 09NeurotensinPeptideLimited. People have taken it in a published study, but fewer than 100 of them. 1 completed trial, 6 people given it.

   nobody was given it1 watch-only study

   • Nobody measured pain or mood in this one. A close relative of neurotensin was infused and the blood flow through fat tissue was measured. It is here because it is one of the very few experiments in which a human being was actually given this peptide. Like the rest of that small set, it looked at the body's machinery rather than at anything a person would notice or care about.

     The numbers A second human infusion study, measuring regional blood flow in adipose tissue after a neurotensin analogue. Reported here because it is part of the small set of experiments in which neurotensin was actually given to human beings, and because like the rest of that set it measured peripheral physiology rather than pain or cognition.

     Acta Physiologica Scandinavica, 1982· number of people not givenobserved only, nobody was given it

Vitamins, minerals, amino acids and botanicals sold over the counter, held to the same standard.

1. 01IdebenoneSupplementModerate. At least one finished study in people, and at least 100 people who took it. 5 completed trials, 732 people given it.

   536 people given it1 trial1 found nothing

   • found nothingIdebenone was tested properly as a brain drug and it did nothing. 536 people with probable Alzheimer's disease took one of three doses or a dummy pill for a year, and nobody involved knew which. Neither of the two main measures, thinking ability and overall clinical change, separated the groups. Nothing else measured separated them either. This is the trial behind the nootropic claim, and the answer was no.

     The numbers 536 patients with probable Alzheimer's disease, one year, multicentre, double blind, randomised, idebenone 120, 240 or 360 mg three times daily versus placebo. No significant differences between groups on either primary outcome, ADAS-Cog and Clinical Global Impression of Change, in the prespecified four-group design, and no differences on any secondary outcome. This is the trial that tests the nootropic claim, and it is negative.

     Neurology, 2003· 536 people

2. 02MCT oilSupplementModerate. At least one finished study in people, and at least 100 people who took it. 1 completed trial, 152 people given it.6 reported

   152 people given it1 trial

   • It helped, and mostly in people without one particular gene. 152 people with Alzheimer's disease took AC-1202 or a dummy for 90 days. Thinking scores were 1.9 points better than the dummy group at day 45. In the 55 people without the APOE4 gene, the gap was 4.77 points at day 45 and 3.36 at day 90. Stomach upsets were more common on treatment. A benefit found inside a subgroup needs its own trial to confirm.

     The numbers 152 participants with mild to moderate Alzheimer's disease, 90 days. AC-1202 significantly raised serum beta-hydroxybutyrate two hours after dosing. In the intention-to-treat population the ADAS-Cog difference from placebo at day 45 was 1.9 points (p equals 0.0235). The effect was concentrated in the 55 participants not carrying the APOE4 allele, where the difference was 4.77 points at day 45 and 3.36 points at day 90. Adverse events, mainly gastrointestinal, were more frequent on treatment.

     Nutrition and Metabolism, 2009· 152 people

3. 03SpermidineSupplementModerate. At least one finished study in people, and at least 100 people who took it. 2 completed trials, 130 people given it.4 reported

   130 people given it2 trials

   • The bigger memory study missed. SmartAge put 100 older adults on 0.9 mg of spermidine a day, or a dummy pill, for 12 months. 89 finished. The main memory test did not change. The gap was minus 0.03. Side effects were the same in both groups. Side looks at word memory and swelling markers are not the result the study was built to test.

     The numbers SmartAge. 100 adults, mean age 69, with subjective cognitive decline randomised to 0.9 mg/day spermidine or placebo for 12 months. Primary mnemonic discrimination difference -0.03 (95% CI -0.11 to 0.05, p = 0.47). Secondary outcomes also null. NCT03094546.

     JAMA Network Open, 2022· 100 people

   • A tiny memory study looked hopeful. 30 older adults who felt their memory was slipping took a spermidine plant extract, or a dummy pill, for three months. Memory scores leaned toward the extract, by a medium amount. The authors said a bigger study would have to confirm it. That bigger study is the next card.

     The numbers Phase IIa pilot. 30 adults aged 60 to 80 with subjective cognitive decline, three months of a spermidine-rich plant extract or placebo. Memory performance contrast mean 0.17 (95% CI -0.01 to 0.35), Cohen's d 0.77. NCT02755246.

     Cortex, 2018· 30 people

4. 04ResveratrolSupplementModerate. At least one finished study in people, and at least 100 people who took it. 14 completed trials, 403 people given it.7 reported

   125 people given it2 trials1 found nothing

   • found nothingThe longest resveratrol trial found a small gain in thinking that has not been confirmed since. 125 women past menopause, aged 45 to 85, took 75 mg twice a day for a year and a dummy pill for another year. Their overall thinking scores came out better on resveratrol, though the gain was small. Blood flow in the brain, fasting insulin and insulin resistance improved too. A 2025 review pooling ten trials in 928 women found no effect on thinking or memory.

     The numbers The longest resveratrol trial published: 125 postmenopausal women aged 45 to 85, 75 mg twice daily for 12 months then crossover for 12 months. Overall cognitive performance improved 33% versus placebo, though the effect size was small (Cohen's d = 0.170, p = 0.005). Resting cerebral blood flow velocity (d = 0.275, p = 0.001), fasting insulin and insulin resistance index also improved. A 2025 meta-analysis of 10 trials in 928 postmenopausal women found no significant effect on cognition or memory, so this result is not settled.

     Clinical Nutrition, 2021· 125 people

   • Blood flow to the front of the brain went up, and thinking did not improve. Twenty-two healthy adults took one dose of 250 or 500 mg. The bigger the dose, the more blood flowed to the frontal cortex during mental tasks, and the tissue appeared to pull more oxygen out of it. Performance on those tasks did not change. What was circulating during the test was mostly broken-down resveratrol, not resveratrol itself.

     The numbers Twenty-two healthy adults, single doses of 250 and 500 mg. Frontal cortex blood flow during cognitive tasks rose dose-dependently by near-infrared spectroscopy, with increased deoxyhaemoglobin suggesting greater oxygen extraction. Cognitive performance itself was not affected. Resveratrol metabolites, not much parent compound, were what circulated during the task.

     American Journal of Clinical Nutrition, 2010· number of people not given

5. 05CreatineSupplementModerate. At least one finished study in people, and at least 100 people who took it. 3 completed trials, 168 people given it.5 reported

   123 people given it1 trial

   • Creatine did nothing for thinking, and it caused more complaints than the dummy did. 123 people took part, about half of them vegetarian. Tests of mental performance came out the same whichever they were given. More of the people on creatine reported side effects than the people on the dummy. Creatine has good evidence behind it for training. This is the trial that tested the brain claim, and the brain claim did not survive it.

     The numbers 123 participants, roughly half vegetarian. The trial reports no cognitive benefit, with more side effects in the creatine arm than placebo.

     BMC Medicine, 2023· 123 people

6. 06Low-dose lithiumSupplementModerate. At least one finished study in people, and at least 100 people who took it. 3 completed trials, 106 people given it.5 reported

   106 people given it3 trials

   • Over two years the untreated group declined and the lithium group did not. 61 older adults living at home with mild memory problems took low-dose lithium or a dummy for two years, nobody knowing which, then were followed two years more. The dummy group got worse on thinking and on daily function. The lithium group stayed steady. Memory and attention were better at two years. Again this is monitored prescription lithium, not a supplement, and 61 people at one site is small.

     The numbers 61 community-dwelling older adults with mild cognitive impairment randomised to subtherapeutic lithium (0.25 to 0.5 mEq/L) or placebo for 2 years double blind, followed a further 24 months single blind. The placebo group declined cognitively and functionally while the lithium group remained stable; lithium was associated with better memory and attention at 24 months and a significant rise in cerebrospinal fluid amyloid-beta 42 at 36 months. Same registration, NCT01055392.

     British Journal of Psychiatry, 2019· 61 people

   • Prescription lithium, at a low monitored dose, moved a brain marker and some thinking scores. 45 people with memory problems took lithium or a dummy for a year, nobody knowing which. Doses were adjusted by blood test to a range below the usual psychiatric one. A tau protein in the spinal fluid fell, and scores on an Alzheimer's scale and on attention tasks improved. 91 percent kept taking it. Note the dose. This is prescription lithium carbonate with blood monitoring, not a trace-dose supplement.

     The numbers 45 participants with amnestic mild cognitive impairment randomised to lithium (titrated to 0.25 to 0.5 mmol/L serum, a subtherapeutic range) or placebo for 12 months. Lithium significantly lowered cerebrospinal fluid phosphorylated tau (p = 0.03) and improved the cognitive subscale of the Alzheimer's Disease Assessment Scale and attention tasks. Tolerability was good and adherence 91 percent. Registered as NCT01055392. Note the dose: prescription lithium carbonate monitored by blood level, not a trace-dose supplement.

     British Journal of Psychiatry, 2011· 45 people

   • This is the only trial at a dose anything like the supplements on sale, and it is one small study. People with Alzheimer's disease took 300 micrograms of lithium once a day for 15 months. The treated group's mental state scores held while the untreated group's fell, with the gap opening from three months and widening after that. No other team has repeated it. The report gives little detail about how it was run. One unrepeated small study at a dose nobody else has tested cannot carry a claim.

     The numbers The only randomised trial located at a dose comparable to supplement products: 300 micrograms of lithium once daily for 15 months in Alzheimer's disease patients. The treated group showed no decrease in mini mental state examination performance while controls declined, with differences appearing from three months and increasing. A single small study, not replicated, and the report gives limited methodological detail.

     Current Alzheimer Research, 2013· number of people not given

   What people using it report

   • The reports split sharply and the split is the most striking thing about this discussion. At the same few milligrams, some people describe a subtle reduction in anxiety and others describe pronounced mental fog, short-term memory problems and sleepiness within an hour. Both are reported by regular posters and neither group is fringe.

   Also measured in animals or in the lab

   • Mostly in mice. In human brain tissue studied after death, lithium was the only metal clearly lower in people with mild memory problems, and amyloid trapped even more of it in Alzheimer's disease. In mice, cutting dietary lithium by about half raised amyloid and tau, damaged nerve connections and sped up memory decline. Giving lithium orotate prevented this in mice. No person was given lithium.

     The numbers Endogenous lithium was the only metal significantly reduced in the brains of individuals with mild cognitive impairment, with bioavailability further reduced in Alzheimer's disease by amyloid sequestration. In mice, reducing cortical lithium by about 50 percent through diet increased amyloid-beta deposition and phospho-tau, activated microglia, caused loss of synapses, axons and myelin, and accelerated cognitive decline, partly through GSK3 beta. Lithium orotate replacement prevented pathology and memory loss in mouse models and ageing wild-type mice. Human post-mortem tissue plus mouse experiments; no human intervention. NIH funded.

     Nature, 2025· animal study

7. 07EGCGSupplementStrong. At least two finished studies in people, and at least 1,000 people who took it. 3 completed trials, 1,172 people given it.5 reported

   87 people given it1 trial1 found nothing

   • found nothingA year of EGCG alongside cognitive training changed almost nothing. 87 adults aged 16 to 34 with Down's syndrome took EGCG or a dummy for a year, both groups doing the training, nobody knowing which. 13 of the 15 cognitive tests showed no difference, and neither did 8 of the 9 everyday skills measures. Gains showed up in visual recognition memory, in self-control, and in one functional academics score. Three positives out of two dozen measures needs a second trial.

     The numbers 87 adults aged 16 to 34 with Down's syndrome randomised to EGCG 9 mg/kg per day or placebo, both with cognitive training, for 12 months; 84 analysed. Differences were not significant on 13 of the 15 tests in the trial battery and on 8 of 9 adaptive skills. Significant gains appeared in visual recognition memory (6.23 percentage points), inhibitory control, and the ABAS-II functional academics score (5.49). No difference in adverse effects between groups. Registered as NCT01699711.

     Lancet Neurology, 2016· 87 people

8. 08PQQSupplementModerate. At least one finished study in people, and at least 100 people who took it. 3 completed trials, 116 people given it.5 reported

   64 people given it1 trial, 1 watch-only

   • PQQ beat a dummy pill on a computer battery of thinking tests, and the industry that sells it ran the study. 64 healthy Japanese adults aged 40 to under 80 took it for twelve weeks and 58 finished. The PQQ group improved on memory, reaction time, attention, mental flexibility, planning and motor speed. No side effects were reported. The authors come from the industry and the product is a branded one. The published record also carries a correction.

     The numbers 64 healthy Japanese adults aged 40 to under 80 randomised for 12 weeks, 58 completed. The PQQ group improved against placebo on Cognitrax composite memory, verbal memory, reaction time, complex attention, cognitive flexibility, executive function and motor speed, and on the two secondary scales. No adverse events. Industry authorship and a branded product, and the record carries a published erratum.

     Journal of the American Nutrition Association, 2022· 64 people

   • Nothing here can be pinned on PQQ. 34 older people with mild memory problems took a six week product that combined PQQ with hydrogen producing minerals, so the two cannot be told apart. A brain growth protein rose inside the treated group but did not clearly pull away from the comparison group, and that was the main thing being measured. Brain oxygen levels rose. One narrow part of a memory scale, orientation, did separate the groups. This is a small trial of a mixture.

     The numbers 34 elderly people with mild cognitive impairment, six weeks. The intervention combined PQQ with hydrogen-producing minerals, so nothing can be attributed to PQQ alone. Serum BDNF, the primary endpoint, rose within the active group (p = 0.01) but the between-group interaction was only a non-significant trend. Cerebral oxygenation rose from 48.4 to 52.8 percent and one ADAS-Cog domain, orientation, showed a significant interaction.

     The Journal of Nutrition, Health and Aging, 2024· 34 peopleobserved only, nobody was given it

9. 09OxaloacetateSupplementModerate. At least one finished study in people, and at least 100 people who took it. 2 completed trials, 112 people given it.4 reported

   30 people given it1 trial1 found nothing

   • found nothingIt was safe and it reached the brain, but thinking did not get better. 30 people with Alzheimer's disease, 15 in each group, took 500 or 1,000 mg twice a day for one month. Both doses were tolerated. The higher dose raised how much sugar the brain took up in several regions and lifted an antioxidant in two of them. Blood levels moved inconsistently. Cognitive scores did not improve. One month in 30 people tests safety and biology, not whether anyone benefits.

     The numbers 30 participants with Alzheimer's disease, 15 per group, given 500 or 1,000 mg twice daily for one month. Both doses were safe and tolerated. The higher dose increased FDG PET glucose uptake across multiple brain regions and raised parietal and frontoparietal glutathione. Blood level changes were not consistent, and cognitive scores did not improve.

     Alzheimer's and Dementia, 2021· 30 people

10. 10Vitamin B12SupplementLimited. People have taken it in a published study, but fewer than 100 of them. 2 completed trials, none stating how many people.4 reported

    0 people given it1 trial1 found nothing

    • found nothingThe vitamins fixed the blood marker and left the brain exactly where it was. 279 outpatients aged 65 and over with mild memory problems and a raised homocysteine level took methylcobalamin with folic acid or a dummy for two years. Homocysteine fell a long way, from about 14 down to about 9. Thinking declined at the same rate in both groups. This is the clearest example on the page of correcting a number in the blood without changing what happens to the person.

      The numbers 279 outpatients aged 65 or over with mild cognitive impairment and raised homocysteine took methylcobalamin 500 micrograms plus folic acid or placebo for 24 months. Homocysteine fell from 13.9 to 9.3 micromol/L, but there was no significant difference in cognitive decline at 24 months. A concrete example of correcting the blood marker without changing the outcome.

      Clinical Nutrition, 2020· number of people not given

11. 11GlyNACSupplementLimited. People have taken it in a published study, but fewer than 100 of them. 2 completed trials, none stating how many people.3 reported

    0 people given it1 trial

    • Older adults improved on several fronts, in a study with nobody to compare them against. Over 24 weeks the supplement corrected a shortage of the body's main antioxidant, and strength, walking speed and thinking all improved. The benefits then faded once people stopped, which at least points back at the supplement. Everybody knew they were taking it, and there was no dummy group.

      The numbers 24 weeks of GlyNAC in older adults corrected glutathione deficiency and improved strength, gait speed and cognition; benefits faded after stopping.

      Clinical and Translational Medicine, 2021· number of people not given

Approved drugs, biologics and hormones that have been measured for this. They are here because leaving them out would misrepresent the evidence, and they are below the peptides because that is not what most people come here to read.

1. 01MinocyclineSmall moleculeModerate. At least one finished study in people, and at least 100 people who took it. 2 completed trials, 966 people given it.

   554 people given it1 trial

   • Tested properly in mild Alzheimer's disease, and it did nothing. 554 people at 32 UK memory clinics were assigned by chance to 400 mg of minocycline, 200 mg, or a dummy pill for two years. Thinking scores fell by roughly four points in every group. Day to day function worsened at the same rate as well. A trial this size would have found a real benefit. Only 28.8 percent finished the high dose against 63.7 percent on the dummy, because most people could not stay on it.

     The numbers 554 randomised, 544 analysed, across 32 NHS memory clinics, 24 months of 400 mg, 200 mg or placebo. Standardised MMSE decline was 4.1 points in the combined minocycline groups against 4.3 on placebo, a difference of 0.1 points (95 percent CI -1.1 to 1.2, p equals 0.90). Activities of daily living worsened equally. Only 28.8 percent completed the 400 mg arm against 63.7 percent on placebo.

     JAMA Neurology, 2020· 554 peoplepoints the wrong way

2. 02Therapeutic Plasma ExchangeProcedureModerate. At least one finished study in people, and at least 100 people who took it. 5 completed trials, 389 people given it.6 reported

   347 people given it2 trials1 found nothing

   • found nothingPlasma exchange slowed decline in Alzheimer disease, and the company that makes the albumin paid for the trial. 347 people were split by chance between three plasma exchange schedules and a sham procedure. Treatment ran weekly for six weeks, then monthly for a year. At 14 months, treated patients lost about half as much everyday function. Thinking scores declined about two thirds less, but that comparison was not strong enough to call. People with moderate disease improved on both measures. People with mild disease did not change.

     The numbers 347 patients randomised 1:1:1:1 from 496 screened into three plasma exchange arms with different albumin and immunoglobulin replacement doses or sham, with six weeks of weekly conventional exchange then twelve months of monthly low-volume exchange. At month 14, treated patients had 52 percent less decline on activities of daily living (p = 0.03) and 66 percent less decline on the cognitive scale (p = 0.06, not significant). Moderate-disease patients improved on both; mild-disease patients did not change. Funded by Instituto Grifols, which manufactures the albumin used.

     Alzheimer's and Dementia, 2020· 347 people

   • The extra measures from AMBAR moved in the same direction as the main ones. All 347 people in the trial were assessed on memory, language, mood and quality of life alongside the main scores. People with mild disease improved on word fluency and on how quickly they processed information. People with moderate disease improved on short term verbal memory. Mood and behaviour changed no differently from the sham group. This is a second look at one trial, and Grifols, which makes the albumin, employed several authors.

     The numbers Secondary analysis of the AMBAR randomised trial reporting the neuropsychological, neuropsychiatric and quality-of-life measures alongside the primary cognitive and functional endpoints.

     Alzheimer's and Dementia, 2022· number of people not given

3. 03AmbroxolSmall moleculeLimited. People have taken it in a published study, but fewer than 100 of them. 2 completed trials, 73 people given it.1 reported

   55 people given it1 trial

   • The proper trial was finally run, and it came back empty. 55 people with Parkinson disease dementia were assigned by chance to 525 mg of ambroxol a day, 1,050 mg, or a dummy, for a year. Nobody knew which. Comparing the high dose against the dummy, nothing separated the groups on thinking scores or on anything else. The drug did hit its target, running the enzyme higher at week 26. So the biology worked and the patients did not benefit. Stomach side effects were more common on ambroxol.

     The numbers The controlled test, and it is null. 52 week phase 2 double-blind placebo-controlled trial, single centre, 75 screened and 55 randomised to ambroxol 525 mg a day, 1,050 mg a day or placebo. Comparing high dose with placebo, there was no evidence of differences between groups on primary or secondary outcomes, the primaries being ADAS-Cog-13 and Clinician's Global Impression of Change. Target engagement was confirmed, with glucocerebrosidase higher at week 26 on drug than placebo. Gastrointestinal adverse events were more frequent on ambroxol, 12 percent of events against 5 percent.

     JAMA Neurology, 2025· 55 people

4. 04OveporextonSmall moleculeModerate. At least one finished study in people, and at least 100 people who took it. 6 completed trials, 441 people given it.

   0 people given it2 trials

   • Attention and memory improved too, but this was a second look at an earlier trial. Researchers went back to the 112 person study and scored thinking tests. People on the drug lapsed in attention far less often than on the dummy, and made many fewer errors on a word pairing task. Executive function tests moved the same way. This was not what the trial was built to answer, so treat it as a lead rather than proof. Only adults were included, and it ran for two months.

     The numbers Secondary analysis of the 112 person phase 2 trial. Placebo-adjusted reductions of 8.6 to 10.8 lapses on the Psychomotor Vigilance Task and 15.5 to 22.5 errors on a paired associate learning test across dose groups, with improvements on executive function tests. Adults 18 to 70 only; 8 weeks.

     JAMA Neurology, 2026· number of people not given

   • This paper worked out how much better attention has to get to count as real, then applied it. Using the two big studies, the team decided two fewer lapses is a change a person would notice. On that yardstick, about two thirds on the drug improved in the first study, against a quarter on the dummy pill. In the second it was roughly three in five, against fewer than one in five. The catch: the maker set the yardstick, then measured its own studies against it.

     The numbers Using phase 3 data, a reduction of 2 or more attention lapses was derived as a meaningful within-person change. On that threshold, 66.9 percent of oveporexton participants against 25.7 percent on placebo improved in First Light, and 57.6 against 17.6 percent in Radiant Light (both P at or below 0.0001). Sponsor-derived threshold applied to sponsor trials.

     Therapeutic Innovation and Regulatory Science, 2026· number of people not given

5. 05BuntanetapSmall moleculeLimited. People have taken it in a published study, but fewer than 100 of them. 1 completed trial, none stating how many people.1 reported

   0 people given it1 trial

   • The early signal was hopeful, and the study was far too small to trust. Fourteen people with early Alzheimer's and 54 with early Parkinson's took buntanetap or a dummy pill. The drug was safe up to 80 mg a day, and the Alzheimer's group scored better on two thinking tests. Here is the problem. Fourteen people cannot settle anything. This was an early look, and its job was to justify a bigger study.

     The numbers Double-blind placebo-controlled study in 14 early Alzheimer's and 54 early Parkinson's patients. Buntanetap was safe and well tolerated up to 80 mg daily, with statistically significant improvement on ADAS-Cog11 and WAIS coding in the Alzheimer's group. Small and exploratory; this is the study that justified the Phase 3.

     Journal of Prevention of Alzheimer's Disease, 2023· number of people not given

6. 06Metformin plus rapamycinSmall moleculePreliminary. Studied in people, but no published study has had people take it. 2 registered with no result.2 reported

   0 people given it1 trial

   • The one trial testing this pair cannot tell the two drugs apart. 30 people are enrolled by AgelessRx, an online company that prescribes these drugs, and it is no longer signing people up. Every group stacks rapamycin and metformin together with low-dose naltrexone, NAD+ up the nose, glutathione on the skin and a house-brand supplement. With six things given at once, no result could be traced to either drug. Nothing has been posted.

     The numbers 30 participants, sponsor AgelessRx (a telehealth prescriber), active not recruiting. Arms combine rapamycin 2 to 6 mg weekly, metformin 500 mg daily, low-dose naltrexone, intranasal NAD+, topical glutathione and a proprietary supplement; primary endpoints VO2 max, a cognitive composite and an inflammation index. Cannot isolate either drug. No results posted.

     ClinicalTrials.gov, 2025· number of people not given

7. 07LamivudineSmall moleculeLimited. People have taken it in a published study, but fewer than 100 of them. 1 completed trial, none stating how many people.3 reported

   0 people given it1 trial

   • This is the only time the idea has been tried in people, and it was not built to show benefit. 12 people with early Alzheimer disease took 300 mg of lamivudine a day. Everybody knew what they were taking and there was nothing to compare against. Safety looked acceptable and thinking scores held steady. A marker of brain inflammation in the spinal fluid fell. The authors say a proper trial with a dummy group is the next step. One author declares an advisory role with a company in this area.

     The numbers The only human study in this line of work. Open label, no control group, 12 participants with early Alzheimer disease on 300 mg of lamivudine daily. Reported a favourable safety profile, stable cognitive measures, a reduction in cerebrospinal fluid GFAP (P = 0.03) suggesting reduced neuroinflammation, and an elevation in plasma amyloid beta 42 to 40 ratio (P = 0.009). The authors state the results warrant a larger placebo-controlled trial. One author discloses a scientific advisory role with a retrotransposon-focused company.

     npj Dementia, 2025· number of people not given

   What people using it report

   • The risk of a hepatitis B flare when stopping gets far too little attention in longevity groups, given how serious it is.
8. 08BromantaneSmall moleculeModerate. At least one finished study in people, and at least 100 people who took it. 3 completed trials, 728 people given it.6 reported

   0 people given it1 trial1 found nothing

   • found nothingThis is the best human evidence bromantane has, and it is thinner than it sounds. People with long-term exhaustion took the drug or a dummy pill for four weeks, then everyone took the dummy for a final week. The authors say it beat the dummy on the main symptoms, and that nobody suffered on stopping. The published summary gives no number of patients and no measure of how big the effect was. What was rated was tiredness, not thinking. The paper is in Russian.

     The numbers The core randomised placebo-controlled record, and the strongest human evidence bromantane has. A randomised blind study in neurasthenia with a wash-out period, 28 days of monotherapy against placebo, and a final week of placebo in all patients. The authors report that ladasten was superior to placebo in the rate and degree of reduction of the main symptoms of asthenic syndrome, and that no withdrawal syndrome appeared after discontinuation. The abstract gives no sample size, no effect size and no p value, and the endpoints are asthenia rating scales, not cognitive tests. Russian language.

     Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova, 2009· number of people not given

9. 09CCL11 BlockadeBiologicPreliminary. Studied in people, but no published study has had people take it. 2 human studies where nobody was given it.5 reported

   nobody was given it1 watch-only study

   • Nobody was given anything here. Researchers measured CCL11 in the blood of 833 older people living at home, 515 in the city of Bordeaux and 318 in the countryside. Country dwellers had higher levels. Among them, higher CCL11 went with worse scores on a standard memory and thinking test. Among city dwellers it did not. Everything was measured at one moment, so there is no way to tell whether the chemical harmed anyone's thinking or simply travelled with something else.

     The numbers 833 community-dwelling older adults: 515 urban from the 3C-Bordeaux cohort and 318 rural from the AMI cohort, with plasma CCL11 by immunoassay and Mini-Mental State Examination as the cognitive measure. CCL11 was higher in rural dwellers, median 145 pg/mL (IQR 115 to 201) versus 103 pg/mL (IQR 85 to 129), p < 0.001. After adjustment, CCL11 was negatively associated with cognitive performance in rural dwellers but not in urban dwellers. Cross-sectional, so direction of effect cannot be established.

     Experimental Gerontology, 2018· 833 peopleobserved only, nobody was given it

   Also measured in animals or in the lab

   • In mice, with one human measurement inside it. Giving a young mouse the blood supply or plasma of an old mouse made its brain adapt less well and harmed learning and memory. The signalling protein CCL11 was picked out. Its blood levels tracked with less new brain cell growth, and it is higher in the blood and spinal fluid of healthy ageing people. Injecting it into young mice slowed new brain cell growth and harmed memory. Funded by the US National Institutes of Health.

     The numbers Mouse, with a human measurement component. Heterochronic parabiosis showed that an old systemic environment or plasma from old mice decreased synaptic plasticity and impaired contextual fear conditioning and spatial learning in young mice. CCL11 was identified as a chemokine whose plasma levels correlated with reduced neurogenesis, and which is increased in the plasma and cerebrospinal fluid of healthy ageing humans. Increasing peripheral CCL11 in young mice decreased neurogenesis and impaired learning and memory. NIH funded.

     Nature, 2011· animal study

10. 10Methylene BlueSmall moleculeLimited. People have taken it in a published study, but fewer than 100 of them. 1 completed trial, 26 people given it.7 reported

    nobody was given it1 watch-only study

    • Methylene blue changed the way brain regions talked to each other on a scan. Nobody then checked whether that made any difference to memory, attention or anything a person would notice. A picture of the brain behaving differently is not a benefit until somebody measures one.

      The numbers Connectivity changes; no clinical cognitive outcome.

      Brain Imaging and Behavior, 2017· number of people not givenobserved only, nobody was given it

11. 11Gpld1BiologicPreliminary. Studied in people, but no published study has had people take it. 2 human studies where nobody was given it.4 reported

    nobody was given it1 watch-only study

    • Nobody was given anything in this study, and it cannot show cause. Healthy men and women aged 65 to 85 were recruited as either inactive or highly active, with movement trackers used to confirm which. GPLD1 was measured once, from fasting blood, at a single visit. Thinking was tested and brains were scanned on the same day. Everything was captured at one moment in time. That design can show that two things travel together. It cannot show that one causes the other.

      The numbers Healthy men and women aged 65 to 85 with body mass index 20 to 35, recruited as either inactive or highly active by a rapid activity assessment score and verified by accelerometry. Circulating GPLD1 was measured from fasting blood at a single clinical visit alongside Mini-Mental State Examination, the NIH Toolbox Cognition Battery, and brain MRI and functional MRI. Cross-sectional and observational: it measures association, not effect.

      GeroScience, 2025· number of people not givenobserved only, nobody was given it

    Also measured in animals or in the lab

    • In mice, with one human measurement inside it. Plasma from old mice that had exercised, given to old mice that had not, passed on the running benefits for new brain cell growth and memory. The enzyme Gpld1, made in the liver, rose after exercise and went with better memory. Raising it in old mice, with no exercise, improved tissue repair and memory. The paper also reports more Gpld1 in the blood of active, healthy older people. Funded by the US National Institutes of Health.

      The numbers Mouse, with a human measurement component. Plasma from exercised aged mice transferred the effects of exercise on adult neurogenesis and cognition to sedentary aged mice. Plasma Gpld1, a liver-derived GPI-degrading enzyme, rose after exercise and correlated with improved cognition; increasing systemic Gpld1 in aged mice improved age-related regenerative and cognitive impairments without exercise. Gpld1 concentrations in blood were also increased in active, healthy elderly humans. NIH funded.

      Science, 2020· animal study

    • In mice, the researchers found what Gpld1 acts on to help memory: an anchored enzyme sitting on the blood vessels of the brain. Copying the age-related rise in that enzyme harmed transport into the brain and harmed memory in young mice, and blunted what Gpld1 could do in old ones. Blocking it brought gene activity in the memory centre back to a young pattern and restored memory. In a mouse model of Alzheimer disease, either raising Gpld1 or blocking that enzyme cut the sticky plaque build-up and improved memory.

      The numbers Mouse. GPI-anchored tissue-nonspecific alkaline phosphatase on the brain vasculature was identified as the Gpld1 substrate mediating cognitive rejuvenation. Mimicking age-related increases in cerebrovascular levels of that enzyme impaired blood-brain transport and cognition in young mice and blunted Gpld1's benefit in aged mice, while inhibiting it restored youthful hippocampal transcriptional signatures and rescued cognition. In an Alzheimer disease model, raising Gpld1 or inhibiting the enzyme reduced amyloid beta pathology and improved cognition.

      Cell, 2026· animal study

Peptides and blends

1. 01FGLPeptideAnimal or lab only. Only animal or lab studies on this page. No study in people yet. 3 animal studies, no human study.3 reported

   2 animal or lab studies

   Measured in animals or in the lab

   • In rats. FGL given after training gave long-lasting memory gains and helped new nerve connections form.

     The numbers FGL given after training produced long-lasting memory improvement in rats and promoted synapse formation via FGFR1.

     Journal of Neuroscience, 2004· animal study

   • In rats. Shots of FGL cut amyloid-type brain damage and memory problems.

     The numbers Systemic FGL reduced amyloid-related pathology and cognitive impairment in a rat model.

     Neuroscience, 2007· animal study

2. 02DihexaPeptideAnimal or lab only. Only animal or lab studies on this page. No study in people yet. 1 animal study, no human study.8 reported

   1 animal or lab study

   What people using it report

   • The negative raised most often is a mounting attention deficit that builds with continued use, with around four weeks mentioned as the point where it becomes a problem, and irritability on non-dosing days.

   Measured in animals or in the lab

   • In rats, the paper that first described dihexa. It could be taken by mouth and got into the brain. It reversed memory loss caused by a drug and grew new connections in the brain's memory center. The journal put a formal warning, an Expression of Concern, on this paper in 2021.

     The numbers Introduced dihexa, an orally active, blood-brain-barrier-permeant AngIV analogue that reversed scopolamine-induced memory deficits and increased hippocampal synaptogenesis in rats. The journal issued an Expression of Concern for this paper in 2021.

     Journal of Pharmacology and Experimental Therapeutics, 2013· animal study

3. 03P21PeptideAnimal or lab only. Only animal or lab studies on this page. No study in people yet. 5 animal studies, no human study.7 reported

   1 animal or lab study

   What people using it report

   • What people report is learning and retention, particularly for procedural material, along with reduced stress and improved sleep. These are a small number of accounts from a small number of people, and the same names recur.

   Measured in animals or in the lab

   • In old rats, 22 to 24 months of age, P021 by mouth over a long time slowed memory loss, brought back new brain cell growth and raised BDNF, a brain growth signal.

     The numbers Chronic oral P021 reduced age-related learning and memory decline in 22 to 24-month-old rats, restored neurogenesis and raised BDNF expression.

     Neurobiology of Aging, 2014· animal study

4. 04Semax / SelankBlendModerate. At least one finished study in people, and at least 100 people who took it. 2 completed trials, 172 people given it.9 reported

   1 animal or lab study

   What people using it report

   • Sharper focus and easier word recall within 20 to 40 minutes of a Semax spray. This is the most common report on the pair.

   Measured in animals or in the lab

   • In rats. One dose of Semax raised BDNF, a brain growth factor, and switched on its receptor in the memory center of the brain. The rats also got better at a learning task. This is the basis for how the Semax half is meant to work, not evidence about the pair.

     The numbers A single dose of 50 micrograms per kilogram raised hippocampal BDNF protein 1.4-fold, trkB phosphorylation 1.6-fold and BDNF mRNA 3-fold in rats, alongside improved conditioned avoidance learning. Rats, Semax alone, one dose. The mechanistic basis of the Semax half, not evidence about the pair.

     Brain Research, 2006· animal study

5. 05SemaxPeptideModerate. At least one finished study in people, and at least 100 people who took it. 4 completed trials, 354 people given it.9 reported

   1 animal or lab study

   Measured in animals or in the lab

   • In rats. One dose raised BDNF, a brain growth protein, about 1.4 times in the memory part of the brain. The rats also learned a task better.

     The numbers A single 50 mcg/kg dose raised hippocampal BDNF protein 1.4-fold, trkB phosphorylation 1.6-fold and BDNF mRNA 3-fold in rats, alongside improved conditioned avoidance learning.

     Brain Research, 2006· animal study

6. 06HumaninPeptideLimited. People have taken it in a published study, but fewer than 100 of them. 1 completed trial, 30 people given it.6 reported

   1 animal or lab study

   Measured in animals or in the lab

   • In worms, making more humanin helped them live longer. In mice, a lab-made version improved metabolic health. In people, humanin in the blood was higher in 18 grown children of people who lived to 100 than in 19 people of the same age. In spinal fluid from just 7 people, it was lower in those with Alzheimer's.

     The numbers Humanin overexpression extended lifespan in C. elegans and an analogue improved metabolic healthspan in mice. In a human Ashkenazi Jewish cohort, circulating humanin was significantly higher in the 18 adult offspring of centenarians than in 19 age-matched controls (p<.05); in a 4-person CSF sample, humanin was lower in Alzheimer's patients than 3 controls (p<.05, very small n).

     Aging (Albany NY), 2020· animal study

7. 07PinealonPeptideLimited. People have taken it in a published study, but fewer than 100 of them. 2 completed trials, none stating how many people.6 reported

   1 animal or lab study

   Measured in animals or in the lab

   • In rats. In the young of mothers with high homocysteine, a harmful blood chemical, Pinealon improved thinking and resistance to cell stress.

     The numbers Improved cognitive function and oxidative-stress resistance in offspring of hyperhomocysteinemic rats.

     International Journal of Clinical and Experimental Medicine, 2012· animal study

8. 08BrimapitidePeptideModerate. At least one finished study in people, and at least 100 people who took it. 4 completed trials, 510 people given it.

   1 animal or lab study

   Measured in animals or in the lab

   • In mice. These mice were bred to get a disease like Alzheimer's. They got a drip of the peptide every three weeks for three or six months. Plaque in the brain dropped at three months but not at six. Memory problems and signs of dying cells were lower at six months. Only 6 to 9 mice were in each group. Nobody has tested this in a person with Alzheimer's.

     The numbers 5XFAD mice given 10 mg/kg intravenously every 3 weeks for 3 or 6 months (6 to 9 per group). Plaque burden fell at 3 months but not at 6; cognitive deficits, cell death markers and IL-1beta were reduced at 6 months. Mouse data only.

     Journal of Alzheimer's Disease, 2018· animal study

9. 09AdropinPeptidePreliminary. Studied in people, but no published study has had people take it. 1 human study where nobody was given it.

   1 animal or lab study

   Measured in animals or in the lab

   • Two findings in one paper. In people, adropin levels tracked with age-related brain damage, which is just a link. The treatment, and the better thinking, was in ageing mice.

     The numbers Read the title as two studies. The human component is a correlation between adropin and ageing-related neuropathology. The intervention, and the cognitive improvement, is in aging mice. Classified here as animal because that is where the treatment was given.

     npj Aging and Mechanisms of Disease, 2021· animal study

Supplements

1. 01PterostilbeneSupplementLimited. People have taken it in a published study, but fewer than 100 of them. 1 completed trial, 80 people given it.4 reported

   1 animal or lab study

   Measured in animals or in the lab

   • In old rats. Rats aged 19 months ate food with a little pterostilbene added. It was picked as the best of seven similar compounds in a cell test. It reversed problems with thinking and with release of the brain chemical dopamine. Rats with more of it in a memory area of the brain had better working memory. This is about thinking in old rats, not about lifespan, and not about people.

     The numbers 19 month old Fischer 344 rats fed diets containing 0.004 or 0.016 percent pterostilbene, selected as the most effective of seven stilbenes in a cell screen. Pterostilbene reversed cognitive behavioural deficits and dopamine release deficits, and working memory correlated with pterostilbene levels in the hippocampus. Aged rats, not people, and a cognition endpoint rather than a lifespan one.

     Journal of Agricultural and Food Chemistry, 2008· animal study

Other compounds

1. 01E5 Plasma FractionProcedureAnimal or lab only. Only animal or lab studies on this page. No study in people yet. 4 animal studies, no human study.4 reported

   2 animal or lab studies

   Measured in animals or in the lab

   • In rats, a fraction of young pig plasma made old organs look much younger on paper. The team first built and checked six tissue-age clocks for rat tissue, from 613 samples. Two of those also work in human tissue. After treatment, the tissue age of blood, heart and liver more than halved. A control centre in the brain moved less but still moved. Blood tests, body function, behaviour and memory all improved. Funded by the US National Institutes of Health with other support.

     The numbers Rat. Six epigenetic clocks were developed and validated for rat tissues from 613 tissue samples, with two clocks trained on an additional 1,366 human tissue samples to work across both species. A young porcine plasma fraction treatment more than halved the epigenetic ages of blood, heart and liver tissue in old rats, with a smaller but statistically significant effect in hypothalamus, accompanied by improvements in biochemical, physiological, behavioural and cognitive measures and a shift in immunoglobulin G N-glycosylation from pro- to anti-inflammatory. NIH supported with non-US government funding.

     GeroScience, 2024· animal study

   • In mice, plasma from human umbilical cords improved how the memory centre of the brain worked and how well old mice did on memory tests. One protein, TIMP2, turned out to be needed for that benefit. This is the other way to do this research: find the single molecule instead of dosing a whole mixture.

     The numbers Mouse. Human umbilical cord plasma improved hippocampal function and cognition in aged mice, and TIMP2 was identified as a specific blood-borne factor necessary for that benefit. This is the alternative research strategy to whole-fraction dosing: find the molecule.

     Nature, 2017· animal study

2. 02Platelet Factor 4BiologicAnimal or lab only. Only animal or lab studies on this page. No study in people yet. 3 animal studies, no human study.4 reported

   2 animal or lab studies

   Measured in animals or in the lab

   • In old male mice, a platelet-rich part of young mouse plasma calmed inflammation in the memory centre of the brain and improved memory. There was more of the protein PF4 in blood from young mice and young people than from older ones. Giving PF4 on its own did the same job in old mice: less inflammation in the memory centre, better memory. A receptor called CXCR3 carries part of the effect. Funded by the US National Institutes of Health.

     The numbers Mouse. Systemic exposure of aged male mice to a platelet-containing fraction of young mouse plasma decreased hippocampal neuroinflammation at transcriptional and cellular levels and improved hippocampal-dependent cognition. Circulating PF4 was elevated in plasma preparations of young mice and young humans relative to older individuals. Systemic PF4 alone attenuated age-related hippocampal neuroinflammation and improved cognition in aged mice, with CXCR3 identified as partly mediating the effect. NIH funded.

     Nature, 2023· animal study

   • In mice, PF4 is described as a protein released during exercise. It restored the growth of new brain cells in the memory centre and brought back memory in old mice. This is one of three papers from separate labs, published within a month, that reached the same conclusion. Funded by the US National Institutes of Health with other support.

     The numbers Mouse. PF4 characterised as an exercise-released factor that rejuvenates hippocampal neurogenesis and restores cognitive function in aged mice. One of three independent papers published within a month reaching a convergent conclusion. NIH funded with non-US government support.

     Nature Communications, 2023· animal study

3. 03Beta-2 MicroglobulinBiologicPreliminary. Studied in people, but no published study has had people take it. 1 human study where nobody was given it.5 reported

   2 animal or lab studies

   Measured in animals or in the lab

   • In mice, with one human measurement. B2M is higher in the blood of ageing people and mice, and in the memory centre of old mice. Injected into young mice, it harmed memory and slowed new brain cell growth. The harm was partly reduced in mice carrying less of the immune-display molecule. Mice bred without B2M kept their memory as they aged and grew more new brain cells when old. Funded by the US National Institutes of Health.

     The numbers Mouse, with human measurement. B2M is elevated in the blood of ageing humans and mice and in the hippocampus of aged mice and young heterochronic parabionts. Exogenous B2M injected systemically or into the hippocampus impaired hippocampal-dependent cognition and neurogenesis in young mice, partly mitigated in mice with reduced cell-surface MHC class I. Absence of endogenous B2M abrogated age-related cognitive decline and enhanced neurogenesis in aged mice. NIH funded.

     Nature Medicine, 2015· animal study

   • In mice, with protein screening of human blood, and in Down syndrome rather than ageing. Blood factors were shown to cause problems at the junctions between nerve cells. There was more B2M in the blood of people with Down syndrome. Giving B2M to ordinary mice caused the same junction and memory problems. Breeding it out, or using an antibody, undid them. B2M blocks a key learning receptor by grabbing one loop of it.

     The numbers Mouse, with human plasma proteomics, in Down syndrome rather than in ageing. Parabiosis and plasma infusion showed blood-borne factors drive synaptic deficits in Down syndrome models. B2M was elevated in human Down syndrome plasma; systemic B2M produced synaptic and memory defects in wild-type mice; genetic deletion or an anti-B2M antibody counteracted the impairments. B2M antagonises NMDA receptor function via the GluN1-S2 loop, and competitive peptides restored receptor-dependent function.

     Cell, 2023· animal study

4. 04ISRIBSmall moleculeAnimal or lab only. Only animal or lab studies on this page. No study in people yet. 3 animal studies, 1 lab study, no human study.4 reported

   2 animal or lab studies

   Measured in animals or in the lab

   • In mice and in a dish. This is the paper that introduced ISRIB. In cells, a tiny dose undid the stress brake on protein making. Treated mice got better at learning places and fear cues. The same paper found that cells under long-term stress survived less well on it. That is the warning sign hidden in the first result.

     The numbers The paper that introduced ISRIB, from a cell-based screen for PERK signalling inhibitors. It reverses the effects of eIF2 alpha phosphorylation with an IC50 of 5 nM, and treated mice showed significant enhancement in spatial and fear-associated learning. The same paper reports that ISRIB reduces the viability of cells under chronic endoplasmic reticulum stress, which is the harm signal hiding in the founding result.

     eLife, 2013· animal studypoints the wrong way

   • In mice. This is the only ageing result. In old mice, ISRIB undid memory loss for places and improved short-term memory. In the memory part of the brain, nerve cells worked more like young ones and regrew contact points. Signs of immune activity in the brain went down. It measured memory, not lifespan. Several authors have business interests in this type of drug.

     The numbers The ageing result, and the only one. ISRIB reversed integrated stress response activation in the aged mouse brain, reversed spatial memory deficits and improved working memory in old mice, and in hippocampus restored intrinsic neuronal electrophysiological properties and spine density while reducing interferon and T cell mediated immune profiles. Memory endpoints, not lifespan or healthspan. Several authors disclose commercial interests in the compound class.

     eLife, 2020· animal study

5. 05Young Plasma InfusionProcedureLimited. People have taken it in a published study, but fewer than 100 of them. 1 completed trial, 18 people given it.6 reported

   1 animal or lab study

   What people using it report

   • The FDA lists what they are sold for: normal ageing, memory loss, dementia, Parkinson disease, multiple sclerosis, Alzheimer disease, heart disease and PTSD. None of those is an approved use.

   Measured in animals or in the lab

   • In mice, this is the experiment the whole young plasma business is built on. Researchers joined the blood supplies of a young mouse and an old mouse. Something carried in old blood slowed new brain cell growth. Putting a young mouse in an old blood supply, or giving it plasma from old mice, made its brain adapt less well and made it worse at learning and at remembering a place where something bad had happened.

     The numbers Mouse. Using heterochronic parabiosis, blood-borne factors were shown to inhibit or promote adult neurogenesis in an age-dependent way. Exposing a young mouse to an old systemic environment or to plasma from old mice decreased synaptic plasticity and impaired contextual fear conditioning and spatial learning. This is the animal experiment the entire young-plasma industry is built on.

     Nature, 2011· animal study

6. 06KlothoBiologicPreliminary. Studied in people, but no published study has had people take it. 2 human studies where nobody was given it.

   1 animal or lab study

   Measured in animals or in the lab

   • In old rhesus monkeys: a single low dose of klotho improved memory.

     The numbers A single low dose improved memory in aged rhesus monkeys.

     Nature Aging, 2023· animal study

7. 07OSKM Cyclic Partial ReprogrammingBiologicAnimal or lab only. Only animal or lab studies on this page. No study in people yet. 6 animal studies, no human study.5 reported

   1 animal or lab study

   Measured in animals or in the lab

   • In mice, switching the four genes on in bursts, only in nerve cells, reversed signs of ageing and improved memory. Limiting the genes to one cell type is one way researchers are trying to make this safer.

     The numbers Mouse. Cyclic four-factor expression restricted to neurons reversed age-associated phenotypes and improved memory performance. Restricting expression to one cell type is one of the strategies being used to narrow the safety window.

     Communications Biology, 2024· animal study

8. 08TIMP2BiologicPreliminary. Studied in people, but no published study has had people take it. 1 human study where nobody was given it.4 reported

   1 animal or lab study

   Measured in animals or in the lab

   • In mice, plasma from human umbilical cords improved how the memory centre of the brain worked and how old mice did on memory tests. The protein doing the work was TIMP2, found in high amounts in cord plasma, in young mouse plasma and in young mouse brains. Given through the body, it reached the brain, helped connections adapt and improved memory in old mice. Taking TIMP2 out of the cord plasma removed the benefit. Funded by the US National Institutes of Health with other support.

     The numbers Mouse. Human umbilical cord plasma improved hippocampal function and cognition in aged mice. TIMP2, enriched in cord plasma, young mouse plasma and young mouse hippocampi, appeared in the brain after systemic administration and increased synaptic plasticity and hippocampal-dependent cognition in aged mice. Depleting TIMP2 removed the benefit of cord plasma. NIH funded with non-US government and non-PHS support.

     Nature, 2017· animal study

9. 09ClusterinBiologicPreliminary. Studied in people, but no published study has had people take it. 2 human studies where nobody was given it, 1 registered with no result.4 reported

   1 animal or lab study

   Measured in animals or in the lab

   • In mice, with one human measurement inside it. Plasma from mice that chose to run, given to mice that did not, quietened inflammation genes in the brain. Protein screening showed a rise in a set of immune system brakes, clusterin among them. Clusterin injected into a vein stuck to the lining of brain blood vessels and quietened those genes, in two different models. Separately, people with memory problems who did six months of structured exercise had more clusterin in their blood.

     The numbers Mouse, with a human observational component. Plasma from voluntarily running mice infused into sedentary mice reduced baseline neuroinflammatory gene expression and experimentally induced brain inflammation. Proteomics showed a coordinated increase in complement cascade inhibitors including clusterin. Intravenous clusterin bound brain endothelial cells and reduced neuroinflammatory gene expression in acute brain inflammation and Alzheimer models. Separately, patients with cognitive impairment who completed six months of structured exercise had higher plasma clusterin. NIH funded.

     Nature, 2021· animal study

10. 10FGF17BiologicPreliminary. Studied in people, but no published study has had people take it. 1 human study where nobody was given it.4 reported

    1 animal or lab study

    Measured in animals or in the lab

    • In mice, pumping young spinal fluid into old brains improved memory. The cells that responded most were the ones that make the insulating sheath around nerve fibres. Young spinal fluid made their parent cells divide and mature, both in the ageing memory centre and in a dish, through one control protein. Pumping in FGF17 on its own was enough to make those cells divide and to lock in long-term memories in old mice. Blocking FGF17 harmed memory in young mice.

      The numbers Mouse. Infusing young cerebrospinal fluid into aged brains improved memory. Oligodendrocytes were the most responsive cell type, and young CSF boosted oligodendrocyte progenitor proliferation and differentiation in the aged hippocampus and in culture, mediated by serum response factor. FGF17 infusion alone was sufficient to induce progenitor proliferation and long-term memory consolidation in aged mice, and FGF17 blockade impaired cognition in young mice.

      Nature, 2022· animal study

11. 11NavitoclaxSmall moleculeModerate. At least one finished study in people, and at least 100 people who took it. 2 completed trials, 137 people given it.2 reported

    1 animal or lab study

    Measured in animals or in the lab

    • In mice. In a mouse model of dementia, clearing worn-out brain support cells stopped the buildup of a harmful protein called tau and prevented memory decline. There is no study of navitoclax for dementia in people.

      The numbers Mouse tau model. Clearing senescent astrocytes and microglia prevented tau deposition and cognitive decline. Mouse only; no human neurodegeneration trial of navitoclax exists.

      Nature, 2018· animal study

12. 12EmpagliflozinSmall moleculeStrong. At least two finished studies in people, and at least 1,000 people who took it. 3 completed trials, 16,738 people given it.4 reported

    1 animal or lab study

    Measured in animals or in the lab

    • In mice. Naturally old male mice given empagliflozin lived 5.9 percent longer on average. They also did better on learning, memory and balance tests, weighed less, and showed fewer signs of worn-out cells in the liver. Their gut bacteria changed too. This is one lab's study, and nobody else has repeated it.

      The numbers The entire mouse lifespan case, from one laboratory. Empagliflozin extended the median survival of male mice by 5.9 percent, improved learning, memory and motor balance, lowered body weight, reduced hepatic P21 and P16, altered gut flora composition and raised short-chain fatty acids. A single-site study, not part of any multi-site replication programme.

      GeroScience, 2024· animal study

13. 13IrisinBiologicLimited. People have taken it in a published study, but fewer than 100 of them. 1 completed trial, 7 people given it.2 reported

    1 animal or lab study

    Measured in animals or in the lab

    • In mice bred to get Alzheimer's. Irisin brought back memory and the way brain cells connect. Mice only.

      The numbers In mouse Alzheimer's disease models, FNDC5/irisin restored synaptic plasticity and memory. Mouse only.

      Nature Medicine, 2019· animal study