1229 replies to this topic

[Wanderer2]

I don't believe that anything used in AD induced animal testing will work in humans. Because, like I just mentioned, it is induced. It is not a natural form of AD. It is not formed as it occurs within humans. Biologically. Unless the study of a chemical is performed on humans with AD. The only thing any clinical trial is actually accomplishing is reversing the "AD like symptoms" that have been induced.

[Consistency]

Blood pressure and particulate air pollution in schoolchildren of Lahore, Pakistan

Abstract

Background

Air pollution is a growing health problem for urban populations in emerging economies. The present study examines the (cross-sectional) relation between blood pressure and particulate air pollution in schoolchildren of Lahore (Pakistan).

Methods

We recruited a sample of 8–12 year-old children (mean age 9.9 years; 45% girls) from two schools in Lahore situated in areas with low (n = 79) and high (n = 100) air pollution, respectively. During the study period (January-April 2009) particulate pollution [PM₁₀ and PM_2.5i.e. particles with aerodynamic diameters below 10 μm or 2.5 μm, respectively] was measured at the school sites with a laser operated device (Metone Aerocet 531). Blood pressure was measured, after 5 minutes of sitting rest, using an automated device (average of 5 consecutive measurements). Spot urine samples were also collected and concentrations of Na and K were measured.

Results

Mean daily values of PM_2.5 were 28.5 μg/m³ (SD: 10.3) and 183 μg/m³ (SD: 30.2), in the low and high pollution areas, respectively. Systolic and diastolic blood pressure were significantly higher in children living in the high pollution area (115.9/70.9 mm Hg) than in the low pollution area (108.3/66.4 mm Hg), independently of age, gender, height, weight, socio-economic status, passive smoking and the urinary concentrations of Na, K, and creatinine.

Conclusions

In 8–12 year-old children, exposure to (traffic-related) air pollution was associated with higher systolic and diastolic blood pressure. These findings, if they persist, might have clinical relevance at older age.

http://www.biomedcen...471-2458/12/378

Brain Inflammation and Alzheimer's-Like Pathology in Individuals Exposed to Severe Air Pollution

Abstract

Air pollution is a complex mixture of gases (e.g., ozone), particulate matter, and organic compounds present in outdoor and indoor air. Dogs exposed to severe air pollution exhibit chronic inflammation and acceleration of Alzheimer's-like pathology, suggesting that the brain is adversely affected by pollutants. We investigated whether residency in cities with high levels of air pollution is associated with human brain inflammation. Expression of cyclooxygenase-2 (COX2), an inflammatory mediator, and accumulation of the 42-amino acid form of b-amyloid (Ab42), a cause of neuronal dysfunction, were measured in autopsy brain tissues of cognitively and neurologically intact lifelong residents of cities having low (n:9) or high (n:10) levels of air pollution. Genomic DNA apurinic/apyrimidinic sites, nuclear factor-κB activation and apolipoprotein E genotype were also evaluated. Residents of cities with severe air pollution had significantly higher COX2 expression in frontal cortex and hippocampus and greater neuronal and astrocytic accumulation of Ab42 compared to residents in low air pollution cities. Increased COX2 expression and Ab42 accumulation were also observed in the olfactory bulb. These findings suggest that exposure to severe airpollution is associated with brain inflammation and Ab 42 accumulation, two causes of neuronal dysfunction that precede the appearance of neuritic plaques and neurofibrillary tangles, hallmarks of Alzheimer's disease.

http://tpx.sagepub.c...ontent/32/6/650

[tham]

The hemorrhoid/varicose vein flavonoid, diosmin.


Flavonoid-mediated presenilin-1 phosphorylation reduces
Alzheimer's disease beta-amyloid production.

" ..... mice treated with diosmin, a glycoside of a flavonoid structurally similar
to luteolin, display significantly reduced Abeta pathology. "

http://www.ncbi.nlm....les/PMC2671567/




The so-called "super bioflavonoid", troxerutin, which has also been used
in hemorrhoid/varicose vein products in Europe (Varemoid, Venoruton),
apparently outperforming diosmin in this respect.

Venoruton vs Daflon: evaluation of effects on quality of
life in chronic venous insufficiency.

http://www.ncbi.nlm....pubmed/16518519



Troxerutin protects against high cholesterol-induced cognitive deficits in mice.

" ..... troxerutin could be recommended as a possible candidate for the prevention
and therapy of cognitive deficits in type 2 diabetes mellitus and Alzheimer's disease. "

http://brain.oxfordj.../134/3/783.long

[tham]

Life Enhancement's Veinotonic II has both troxerutin and diosmin, in
addition to horse chestnut and Centellia asiatica.

http://www.life-enha...i-veinotonic-ii

http://www.iherb.com...-Capsules/14715



Diosmin reduces glycation.

"We are all latent diabetics."

http://www.life-enha...lps-reduce-ages

[Logic]

Colostrinin: a proline-rich polypeptide (PRP) complex isolated from ovine colostrum for treatment of Alzheimer's disease. A double-blind, placebo-controlled study.
http://www.ncbi.nlm..../10608295Leszek

J, Inglot AD, Janusz M, Lisowski J, Krukowska K, Georgiades JA.

Source
The Psychiatric Unit, University Medical School, Wroclaw, Poland.

Abstract
A proline-rich polypeptide (PRP) complex, subsequently called Colostrinin, was isolated from ovine colostrum. The complex showed immunomodulatory properties in mice, rats, and chickens, inducing maturation and differentiation of thymocytes. It was recently found that Colostrinin is a cytokine-like factor that acts as an inducer of interferon gamma (IFN-gamma) and other cytokines in human peripheral blood and cord blood leukocyte cultures and has psycho-immuno-enhancing activity in volunteers. These observations prompted us to study the effect of Colostrinin on patients with Alzheimer's disease (AD). Forty six AD patients were divided into 3 groups and randomly assigned to receive orally either Colostrinin (100 microg per tablet, every second day), commercially available bioorganic selenium (100 microg selenium per tablet, every second day) or placebo tablets. One cycle of the treatment lasted 3 weeks and was separated from the next cycle by a 2 week hiatus. Each patient received 10 cycles of treatment during the year of the clinical trial. Outcomes were assessed by psychiatrists blinded to the treatment assignment. Eight of the 15 AD patients treated with Colostrinin improved and in the 7 others the disease had stabilized. In contrast, none of the 31 patients from the selenium or placebo groups with similar mild or moderate AD improved. The administration of selenium promoted stabilization in 13 of the 15 patients, whereas in the placebo group only 8 of the 16 patients were stabilized at the 12 month trials end-evaluation. Colostrinin was found to be a remarkably safe drug. Mild and transient effects were anxiety, stimulation, insomnia, and tiredness. The results obtained showed that oral administration of Colostrinin improves the outcome of AD patients with mild to moderate dementia. The results are very encouraging and deserve further research.


--------------


New insights into clinical trial for Colostrinin in Alzheimer's disease.
http://www.ncbi.nlm....pubmed/19262960

RESULTS:
The Full Sample Analysis at week 15 showed a stabilizing effect of CLN on cognitive function in ADAS-cog (p = 0.02) and on daily function in IADL (p = 0.02). The overall patient response was also in favor of CLN (p = 0.03). Patients graded as mild on entry also showed a superior response of ADAS-cog compared to more advanced cases (p = 0.01). Data derived from microarray network analysis show that CLN elicits highly complex and multiphasic changes in the cells' transcriptome. Importantly, transcriptomal analysis showed that CLN alters gene expression of molecular networks implicated in Abeta precursor protein synthesis, Tau phosphorylation and increased levels of enzymes that proteolitically eliminate Abeta. In addition, CLN enhanced the defense against oxidative stress and decreased expression of inflammatory chemokines and cytokines, thereby attenuating inflammatory processes that precede Alzheimer's and other neurological diseases.

CONCLUSION:
Together these data suggest that CLN has promising potential for clinical use in prevention and therapy of Alzheimer's and other age-associated central nervous system diseases.

[tham]

Effect of piracetam on cognitive performance in patients undergoing bypass surgery.

http://www.ncbi.nlm.nih.gov/m/pubmed



Piracetam prevents cognitive decline in coronary artery bypass.

http://www.ncbi.nlm....pubmed/16996947



Cerebroprotective effect of piracetam in patients undergoing coronary bypass burgery.

" Piracetam has a cerebroprotective effect in patients undergoing coronary artery
bypass surgery with the use of cardiopulmonary bypass. It reduces an early
postoperative substantial decline of neuropsychological abilities. "

http://www.ncbi.nlm....pubmed/18971883



Cerebroprotective effect of piracetam in patients undergoing open heart surgery.

" Piracetam had no cerebroprotective effect in patients undergoing open heart
surgery. Unlike the patients who underwent coronary surgery, piracetam did not
reduce the early postoperative decline of neuropsychological abilities in heart
valve patients. "

http://www.ncbi.nlm....pubmed/21597409

[mag1]

The Effect of an Aloe Polymannose Multinutrient Complex on Cognitive and Immune Functioning in Alzheimer’s Disease, (J Alzheimers Dis. 2013;33(2):393-406.).

[tham]

The Aging Eye: Common Degenerative Mechanisms
Between the Alzheimer's Brain and Retinal Disease

http://www.iovs.org/...1/871.full.html



Minocycline and AD

'' At age 49, I was in stage 3/4 of AD (see sticky above) onset. The cause
was an undiagnosed case of Lyme Disease, and long term treatment
with Minocycline has given me my brain back. Minocycline prevents
brain cell death and combats the inflammatory processes that cause AD.
I can't emphasize this strongly enough:

Minocycline is effective against AD !

Minocycline is an effective treatment and the sooner you or a loved one
begin treatment, the sooner the disease progression can be stopped
and/or reversed. ''

http://www.healthboa...cycline-ad.html



Can minocycline prevent the onset of Alzheimer's disease ?

http://www.ncbi.nlm....pubmed/21416497




Minocycline affects microglia activation, Abeta deposition, and behavior in APP-tg mice.

http://www.ncbi.nlm....pubmed/16534778


Inhibition of microglial activation protects hippocampal neurogenesis and improves
cognitive deficits in a transgenic mouse model for Alzheimer's disease.

'' These results suggest a role for microglia in Aβ-related functional deficits and
in suppressing the survival of new neurons, and show that modulation of
microglial function with minocycline can protect hippocampal neurogenesis
in the presence of Aβ pathology. ''


http://www.ncbi.nlm....pubmed/22584394



Minocycline reduces the development of abnormal tau species in
models of Alzheimer's disease.

http://www.fasebj.or...t/23/3/739.long


Minocycline attenuates neuronal cell death and improves cognitive
impairment in Alzheimer's disease models.

http://www.nature.co...l/1301377a.html


Anti-apoptotic and anti-oxidative mechanisms of minocycline against
sphingomyelinase/ceramide neurotoxicity: implication in Alzheimer's
disease and cerebral ischemia.

http://www.ncbi.nlm....ubmed/22583533/


Minocycline corrects early, pre-plaque neuroinflammation and inhibits
BACE-1 in a transgenic model of Alzheimer's disease-like amyloid pathology.

http://www.jneuroinf.../content/9/1/62



Anti-inflammatory impact of minocycline in a mouse model of tauopathy.

http://www.frontiers...2010.00136/full



Neuroprotection by Minocycline Caused by Direct and Specific
Scavenging of Peroxynitrite

http://www.jbc.org/c...286/7/4991.full



Minocycline and neurodegenerative diseases.

http://www.ncbi.nlm....pubmed/18977395

[ta5]

Maybe melatonin would help:

Yes, maybe. The full text is available:


Int J Mol Sci. 2013 Jul 12;14(7):14575-93. doi: 10.3390/ijms140714575.

Melatonin in Alzheimer's disease.

Lin L, Huang QX, Yang SS, Chu J, Wang JZ, Tian Q.
Department of Pathology and Pathophysiology, Tongji Medical College, Huazhong University of
Science and Technology, Wuhan 430030, China.

Alzheimer's disease (AD), an age-related neurodegenerative disorder with progressive cognition deficit, is characterized by extracellular senile plaques (SP) of aggregated β-amyloid (Aβ) and intracellular neurofibrillary tangles, mainly containing the hyperphosphorylated microtubule-associated protein tau. Multiple factors contribute to the etiology of AD in terms of initiation and progression. Melatonin is an endogenously produced hormone in the brain and decreases during aging and in patients with AD. Data from clinical trials indicate that melatonin supplementation improves sleep, ameliorates sundowning and slows down the progression of cognitive impairment in AD patients. Melatonin efficiently protects neuronal cells from Aβ-mediated toxicity via antioxidant and anti-amyloid properties. It not only inhibits Aβ generation, but also arrests the formation of amyloid fibrils by a structure-dependent interaction with Aβ. Our studies have demonstrated that melatonin efficiently attenuates Alzheimer-like tau hyperphosphorylation. Although the exact mechanism is still not fully understood, a direct regulatory influence of melatonin on the activities of protein kinases and protein phosphatases is proposed. Additionally, melatonin also plays a role in protecting the cholinergic system and in anti-inflammation. The aim of this review is to stimulate interest in melatonin as a potentially useful agent in the prevention and treatment of AD.
PMID: 23857055

Edited by ta5, 20 August 2013 - 03:20 AM.

[tham]

Effects of minocycline on endogenous neural stem cells after experimental stroke.

http://www.ncbi.nlm....pubmed/22542871



Prevention of hypoglycemia-induced neuronal death by minocycline.

'' Diabetic patients who attempt strict management of blood glucose levels
frequently experience hypoglycemia. Severe and prolonged hypoglycemia
causes neuronal death and cognitive impairment. There is no effective tool
for prevention of these unwanted clinical sequelae.

Minocycline, a second-generation tetracycline derivative, has been recognized
as an anti-inflammatory and neuroprotective agent in several animal models
such as stroke and traumatic brain injury.


1) Minocycline is neuroprotective, even when the treatment is initiated 6 hours
after hypoglycemia;

2) Minocycline prevents microglial activation after hypoglycemia; and

3) Minocycline prevents cognitive impairment even at several weeks after hypoglycemia.

Thus, the present study suggests that prevention of microglial activation by minocycline
has a strong therapeutic potential for prevention of hypoglycemia-induced brain injury. ''


http://www.jneuroinf...content/9/1/225




Evaluation of late cognitive impairment and anxiety states following traumatic
brain injury in mice: the effect of minocycline.

http://www.ncbi.nlm....pubmed/22314279





'' Medication Protects Men From Seduction By Dangerous Women. ''

http://www.popsci.co...ttractive-women



Minocycline, a microglial inhibitor, reduces ‘honey trap’ risk in
human economic exchange.

http://www.nature.co.../srep01685.html


Minocycline modulates human social decision-making: possible
impact of microglia on personality-oriented social behaviors.

http://www.plosone.o...al.pone.0040461


Does minocycline, an antibiotic with inhibitory effects on microglial activation,
sharpen a sense of trust in social interaction ?

'' These results suggest that minocycline led to more rational decision-making
strategies, possibly by increasing emotion regulation. Since minocycline is a
well-known inhibitor of microglial activation, our findings may open a new
optional pathway for treating mental states in which a component of rational
decision making is impaired. ''

http://www.ncbi.nlm....pubmed/21956241



Minocycline reduces ethanol drinking.

http://www.ncbi.nlm....les/PMC3098317/



Novel therapeutic targets in depression: minocycline as a candidate treatment.

http://www.ncbi.nlm....pubmed/22963995



Minocycline as adjunctive therapy for patients with unipolar psychotic
depression: an open-label study.

http://www.ncbi.nlm....pubmed/22349578



Minocycline: therapeutic potential in psychiatry.

http://www.ncbi.nlm....pubmed/22486246

[tham]

Pharmacological stabilization of intracranial aneurysms in mice: a feasibility study.


'' Minocycline and doxycycline significantly reduced rupture rates
(vehicle versus doxycycline = 80% versus 35%; vehicle versus
minocycline = 73% versus 24%) without affecting the overall
incidence of aneurysms. ''


http://www.ncbi.nlm....pubmed/22798328

[MrHappy]

http://beaker.sanfor...eimers-disease/

Reversing the loss of brain connections in Alzheimer’s disease

The first experimental drug to boost brain synapses lost in Alzheimer’s disease has been developed by researchers at Sanford-Burnham. The drug, called NitroMemantine, combines two FDA-approved medicines to stop the destructive cascade of changes in the brain that destroys the connections between neurons, leading to memory loss and cognitive decline.
The decade-long study, led by Stuart A. Lipton, M.D., Ph.D., professor and director of the Del E. Webb Center for Neuroscience, Aging, and Stem Cell Research, who is also a practicing clinical neurologist, shows that NitroMemantine can restore synapses, representing the connections between nerve cells (neurons) that have been lost during the progression of Alzheimer’s in the brain. The research findings are described in a paper published June 17 by the Proceedings of the National Academy of Sciences of the United States of America (PNAS).
The focus on a downstream target to treat Alzheimer’s, rather than on amyloid beta plaques and neurofibrillary tangles—approaches which have shown little success—“is very exciting because everyone is now looking for an earlier treatment of the disease,” Lipton said. “These findings actually mean that you might be able to intercede not only early but also a bit later.” And that means that an Alzheimer’s patient may be able to have synaptic connections restored even with plaques and tangles already in his or her brain.
Targeting lost synapses
In their study, conducted in animal models as well as brain cells derived from human stem cells, Lipton and his team mapped the pathway that leads to synaptic damage in Alzheimer’s. They found that amyloid beta peptides, which were once thought to injure synapses directly, actually induce the release of excessive amounts of the neurotransmitter glutamate from brain cells called astrocytes that are located adjacent to the nerve cells.
Normal levels of glutamate promote memory and learning, but excessive levels are harmful. In patients suffering from Alzheimer’s disease, excessive glutamate activates extrasynaptic receptors, designated eNMDA receptors (NMDA stands for N-methyl-D-aspartate), which get hyperactivated and in turn lead to synaptic loss.
How NitroMemantine works
Lipton’s lab had previously discovered how a drug called memantine can be targeted to eNMDA receptors to slow the hyperactivity seen in Alzheimer’s. This patented work contributed to the FDA approval of memantine in 2003 for the treatment of moderate to severe Alzheimer’s disease. However, memantine’s effectiveness has been limited. The reason, the researchers found, was that memantine—a positively charged molecule—is repelled by a similar charge inside diseased neurons; therefore, memantine gets repelled from its intended eNMDA receptor target on the neuronal surface.
In their study, the researchers found that a fragment of the molecule nitroglycerin—a second FDA-approved drug commonly used to treat episodes of chest pain or angina in people with coronary heart disease—could bind to another site that the Lipton group discovered on NMDA receptors. The new drug represents a novel synthesis connecting this fragment of nitroglycerin to memantine, thus representing two FDA-approved drugs connected together. Because memantine rather selectively binds to eNMDA receptors, it also functions to target nitroglycerin to the receptor. Therefore, by combining the two, Lipton’s lab created a new, dual-function drug. The researchers developed 37 derivatives of the combined drug before they found one that worked, Lipton said.
By shutting down hyperactive eNMDA receptors on diseased neurons, NitroMemantine restores synapses between those neurons. “We show in this paper that memantine’s ability to protect synapses is limited,” Lipton said, “but NitroMemantine brings the number of synapses all the way back to normal within a few months of treatment in mouse models of Alzheimer’s disease. In fact, the new drug really starts to work within hours.”
To date, therapies that attack amyloid plaques and neurofibrillary tangles have failed. “It’s quite disappointing because I see really sick patients with dementia. However, I’m now optimistic that NitroMemantine will be effective as we advance to human trials, bringing new hope to both early and later-stage Alzheimer’s patients,” Lipton said.
Talantova, M., Sanz-Blasco, S., Zhang, X., Xia, P., Akhtar, M., Okamoto, S., Dziewczapolski, G., Nakamura, T., Cao, G., Pratt, A., Kang, Y., Tu, S., Molokanova, E., McKercher, S., Hires, S., Sason, H., Stouffer, D., Buczynski, M., Solomon, J., Michael, S., Powers, E., Kelly, J., Roberts, A., Tong, G., Fang-Newmeyer, T., Parker, J., Holland, E., Zhang, D., Nakanishi, N., Chen, H., Wolosker, H., Wang, Y., Parsons, L., Ambasudhan, R., Masliah, E., Heinemann, S., Pina-Crespo, J., & Lipton, S. (2013). A induces astrocytic glutamate release, extrasynaptic NMDA receptor activation, and synaptic loss Proceedings of the National Academy of Sciences DOI: 10.1073/pnas.1306832110

[niner]

The new drug represents a novel synthesis connecting this fragment of nitroglycerin to memantine, thus representing two FDA-approved drugs connected together.

Very cool work. This statement seems to imply that combining two approved drugs equals a "pre-approved" drug, but any time a drug molecule is altered, it will need to go through the same approval process. This sounds like a very promising compound, but how long until it sees the light of day? Ten years? That sucks if you need it now.

[Raptor87]

Is choline useless in alzheimers due to failing receptors in the brain? Or should you eat choline anyway?

[lostfalco]

Is choline useless in alzheimers due to failing receptors in the brain? Or should you eat choline anyway?

Choline is one of the best things you can take for cell membrane health. Extremely important apart from it's role as a neurotransmitter. =)

Check out phosphatidylcholine (phospholipid/membrane health) and acetylcholine (neurotransmitter) for more info.

http://en.wikipedia....phatidylcholine
http://examine.com/s...hatidylcholine/

http://en.wikipedia....i/Acetylcholine

[niner]

Here's a systematic review that looked at lecithin in dementia. Not exactly choline, but lostfalco mentioned PC, for which lecithin is a source. The results were mixed, but not entirely negative. Seems like lecithin, and possibly purified PC belongs in the "couldn't hurt, might help" category, although the odds of it helping are low; perhaps better for MCI than frank dementia.

Cochrane Database Syst Rev. 2003;(3):CD001015.
Lecithin for dementia and cognitive impairment.
Higgins JP, Flicker L.

MRC Biostatistics Unit, Institute of Public Health, Robinson Way, Cambridge, Cambridgeshire, UK, CB2 2SR.

BACKGROUND:

Alzheimer's disease sufferers have been found to have a lack of the enzyme responsible for converting choline into acetylcholine within the brain. Lecithin is a major dietary source of choline, so extra consumption may reduce the progression of dementia.
OBJECTIVES:

To determine the efficacy of lecithin in the treatment of dementia or cognitive impairment.
SEARCH STRATEGY:

The Cochrane Dementia and Cognitive Improvement Group's Specialized Register was searched on 15 May 2002 using the terms lecithin and phosphaditylcholine. This contains records from all major databases and many trials databases. Reference lists and relevant books have been examined.
SELECTION CRITERIA:

All unconfounded, randomized trials comparing lecithin with placebo in a treatment period longer than one day, in patients with dementia of the Alzheimer type, vascular dementia, mixed vascular and Alzheimer's disease, unclassified or other dementia or unclassified cognitive impairment not fulfilling the criteria for dementia are eligible for inclusion.
DATA COLLECTION AND ANALYSIS:

Data were extracted by two independent reviewers and cross-checked. Meta-analyses were performed when more than one trial provided data on a comparable outcome on sufficiently similar patients. Random effects analyses were performed whenever heterogeneity between results appeared to be present. Standardised differences in mean outcome measures were used due do the use of different scales and periods of treatment. Odds ratios for dichotomous data were pooled using the Mantel-Haenszel or DerSimonian and Laird methods.
MAIN RESULTS:

Twelve randomized trials have been identified involving patients with Alzheimer's disease (265 patients), Parkinsonian dementia (21 patients) and subjective memory problems (90 patients). No trials reported any clear clinical benefit of lecithin for Alzheimer's disease or Parkinsonian dementia. Few trials contributed data to meta-analyses. The only statistically significant result was in favour of placebo for adverse events, based on one trial, which appears likely to be a spurious result. A dramatic result in favour of lecithin was obtained in a trial of subjects with subjective memory problems.
REVIEWER'S CONCLUSIONS:

Evidence from randomized trials does not support the use of lecithin in the treatment of patients with dementia. A moderate effect cannot be ruled out, but results from the small trials to date do not indicate priority for a large randomized trial.

PMID: 12917896

[Raptor87]

Is choline useless in alzheimers due to failing receptors in the brain? Or should you eat choline anyway?

Choline is one of the best things you can take for cell membrane health. Extremely important apart from it's role as a neurotransmitter. =)

Check out phosphatidylcholine (phospholipid/membrane health) and acetylcholine (neurotransmitter) for more info.

http://en.wikipedia....phatidylcholine
http://examine.com/s...hatidylcholine/

http://en.wikipedia....i/Acetylcholine

Ok! My mom seems to be speaking the wrong language to wrong people and it's freaking me out. She is above her 50´s so I am thinking that perhaps she is pre- alzheimers. I am worried! I was thinking in ordering some deprenyl for her (if it is a cognitive issue) but I am not really sure what to do or if there is a problem.

What works on choline receptors then?

[MrHappy]

http://www.ncbi.nlm....ubmed/21130529/

Dietary ketosis enhances memory in mild cognitive impairment.

We randomly assigned 23 older adults with mild cognitive impairment to either a high carbohydrate or very low carbohydrate diet. Following the 6-week intervention period, we observed improved verbal memory performance for the low carbohydrate subjects (p = 0.01) as well as reductions in weight (p < 0.0001), waist circumference (p < 0.0001), fasting glucose (p = 0.009), and fasting insulin (p = 0.005). Level of depressive symptoms was not affected. Change in calorie intake, insulin level, and weight were not correlated with memory performance for the entire sample, although a trend toward a moderate relationship between insulin and memory was observed within the low carbohydrate group. Ketone levels were positively correlated with memory performance (p = 0.04). These findings indicate that very low carbohydrate consumption, even in the short term, can improve memory function in older adults with increased risk for Alzheimer's disease. While this effect may be attributable in part to correction of hyperinsulinemia, other mechanisms associated with ketosis such as reduced inflammation and enhanced energy metabolism also may have contributed to improved neurocognitive function. Further investigation of this intervention is warranted to evaluate its preventive potential and mechanisms of action in the context of early neurodegeneration.

[tham]

Treatment with enhanced external counterpulsation improves
cognitive functionsin chronic heart failure patients.


'' Enhanced external counter pulsation resulted in improvement in all
domains of cognitive functions except verbal and visual memory tests. ''


'' It was shown that impaired cardiac function can adversely affect the brain via
decreased perfusion. Adjusted global cognitive performance, as well as
performance in visuoconstruction and motor speed, was significantly directly
associated with LVEF. Patients with low EF had worse cognitive performance,
in particular in global and motor speed cognitive scores. Decreased EF may
exacerbate cerebral hypoperfusion. It was shown in this study that patients
with EECP treatment had higher LVEF and decreased BNP levels,
which are signs of better heart function. Levenson et al. reported that EECP
therapy reduces carotid arterial stiffness and resistance in patients with
stable coronary artery disease and augments carotid blood flow and
concomitantly reduces the regional vascular resistance.

In our study, the EECP treatment group also had better cognition after the treatment
period. We assumed that the treatment with EECP improved heart functions, which
may increase the brain perfusion in grey and white matter, which results in better
cognitive functions. Patients in the control group had neither better LVEFs nor lower
BNP levels after seven weeks. These recovery differences between the EECP group
and control group seemed to support our theory of why EECP and medical treatment
had better effects on the executive function of cognition compared to medical treatment
alone in ischemic heart failure. ''


http://old.tkd.org.t...=2913&dosya=245

Edited by tham, 24 November 2013 - 07:06 PM.

[tham]

Brain aging and midlife tofu consumption.


'' Poor cognitive test performance, enlargement of ventricles and low brain
weight were each significantly and independently associated with higher
midlife tofu consumption. ''


http://www.ncbi.nlm....pubmed/10763906




Association of midlife blood pressure to late-life
cognitive decline and brain morphology.


'' Midlife SBP is a significant predictor of both decline in cognitive function
and MR volumetric measures of brain atrophy in late life ..... long-term impact
of elevated SBP on decline in late-life neurobehavioral functioning is likely
to be mediated through its chronic, negative effect on structural
characteristics of the brain.''

http://www.ncbi.nlm..../pubmed/9781518

[tham]

The full text of the above study, based on the Honolulu-Asia Aging Study.


Brain aging and midlife tofu consumption.

http://www.healthmeg...nArticle260.pdf



Weston Price on the above study.

Soy and the Brain.

'' High amounts of protein tyrosine kinases are found in the hippocampus,
a brain region involved with learning and memory. One of soy’s primary
isoflavones, genistein, has been shown to inhibit tyrosine kinase in the
hippocampus, where it blocked "long-term potentiation," a mechanism
of memory formation. ''

http://www.westonapr...y-and-the-brain



The researchers above implicates isoflavones, but this source says
it is more likely aluminium.

'' The results of this preliminary investigation suggest that the aluminum
concentration in soy products is increased slightly by cooking, particularly
in an aluminum pot, and strongly (as much as 15-fold) by some methods
of tofu production. ''

http://www.vegsource...brain_aging.htm

[tham]

Sea cucumbers would be a good part of a brain supportive diet.



'' Sea Cucumbers Fast Track Organ Regrowth By Healing Their Wounds. ''

http://www.scienceda...71017194617.htm



Regeneration of the radial nerve cord in the sea cucumber Holothuria glaberrima.

http://link.springer...6/1471-213X-9-3



Regeneration of the enteric nervous system in the
sea cucumber Holothuria glaberrima.

http://www.ncbi.nlm....pubmed/10205023

[tham]

Clinical study of Reinhartdt and sea cucumber capsule combined
with donepezil in treating Alzheimer's disease.

http://www.ncbi.nlm....ubmed/17342994/



A double blind study on the Reinhardt and sea cucumber
capsule in treating dementia of the aged.

http://en.cnki.com.c...BJ200001004.htm



Clinical study of combined treatment with compound Reinhartdt and
Sea Cucumber Capsule and donepezil for vascular dementia.

http://www.ncbi.nlm....pubmed/17990453




The protective effect of eicosapentaenoic acid-enriched phospholipids from sea
cucumber Cucumaria frondosa on oxidative stress in PC12 cells and SAMP8 mice.

http://www.ncbi.nlm....ubmed/24231470/




The SAMP8 mouse: a model of Alzheimer disease ?

http://www.ncbi.nlm....pubmed/12014843



From aging to Alzheimer's disease: unveiling "the switch"
with the senescence-accelerated mouse model (SAMP8).

http://www.ncbi.nlm....ubmed/19096160/









]

[tham]

Serrapeptase and nattokinase intervention for relieving Alzheimer's
disease pathophysiology in rat model.

http://www.ncbi.nlm....ubmed/23821590/




Discovery Sheds Light On Why Alzheimer's Drugs Rarely Help.

http://www.scienceda...30701100602.htm



Copper Can Protect Against Alzheimer's Disease.

http://www.scienceda...30217083905.htm

Edited by tham, 25 December 2013 - 05:01 AM.

[tham]

Diabetes Raises Alzheimer’s Proteins.

http://www.worldheal...imers-proteins/



Salk study finds diabetes raises levels of proteins linked to Alzheimer's features.

http://www.salk.edu/...hp?press_id=586



Diabetes exacerbates amyloid and neurovascular pathology in aging-accelerated mice.

http://www.ncbi.nlm....les/PMC3500443/




Diabetes and accelerated aging: Can we stop or turn back the clock ?

http://demystifyingm...r_20130225.html



Diabetes: A model of oxidative accelerated aging.

http://www.ncbi.nlm...._Article_16.pdf



Apparent Accelerated Aging of Human Collagen in Diabetes Mellitus.

http://diabetes.diab...2.full.pdf html




'' These 4 Foods Accelerate Aging. ''

http://www.disclose....NG_beware/88894

[cudBwrong]

Various acetylcholinesterase (AchE) inhibitors are being investigated for the treatment of Alzheimer's

A computer simulation ("in silico") study predicts that quercetin should be a better AchE inhibitor,
with fewer side effects, than other drugs under investigation.

http://www.ncbi.nlm....pubmed/24563598

J Young Pharm. 2013 Dec;5(4):173-9. doi: 10.1016/j.jyp.2013.11.005. Epub 2013 Dec 15.
In silico QSAR analysis of quercetin reveals its potential as therapeutic drug for Alzheimer's disease.

Islam MR¹, Zaman A², Jahan I³, Chakravorty R⁴, Chakraborty S⁵.
Author information

• ¹International Max Planck Research School for Neurosciences, University of Göttingen, 37077 Göttingen, Germany ; Department of Biochemistry and Molecular Biology, University of Dhaka, Dhaka 1000, Bangladesh.
• ²University of Texas Southwestern Medical Center, Dallas, TX 75235, USA.
• ³Molecular Biology Lab, Department of Biochemistry and Molecular Biology, University of Dhaka, Dhaka 1000, Bangladesh.
• ⁴Department of EEE, University of Melbourne, National ICT Australia, Victoria 3010, Australia.
• ⁵Department of Biochemistry and Molecular Biology, University of Dhaka, Dhaka 1000, Bangladesh.

Abstract


Acetylcholine-esterase (AchE) inhibitors are one of the most potent drug molecules against Alzheimer's disease (AD). But, patients treated with current AchE inhibitors often experience severe side effects. Quercetin is a plant flavonoid compound which can act as AchE inhibitor and it may be a better alternative to current AchE inhibitors in terms of effectiveness with no or fewer side effects.
AIMS:

The aim of the study was to compare quercetin with conventional AchE inhibitors to search for a better drug candidate.
METHODS AND MATERIALS:

Physico-chemical properties of conventional drugs and quercetin were predicted using bioinformatics tools. Molecular docking of these compounds on the active site of AchE was performed using AutoDock and comparative analysis was performed. Later, modification on the basic structure of quercetin with different functional groups was done to perform QSAR analysis.
RESULT AND DISCUSSION:

Quercetin showed a similar drug likeness score to the conventional drugs. The binding strength for quercetin in the active site of the enzyme was -8.8 kcal/mol, which was considerably higher than binding scores for some of the drugs such as donepezil (binding score -7.9 kcal/mol). Fifteen hydrogen bonds were predicted between quercetin and the enzyme whereas conventional drugs had fewer or even no hydrogen bonds. It implies that quercetin can act as a better inhibitor than conventional drugs. To find out even better inhibitor, similar structures of quercetin were searched through SIMCOMP database and a methylation in the 4-OH position of the molecule showed better binding affinity than parent quercetin. Quantitative structure activity relationship study indicated that O-4 methylation was specifically responsible for better affinity.
CONCLUSION:

This in silico study has conclusively predicted the superiority of the natural compound quercetin over the conventional drugs as AchE inhibitor and it sets the need for further in-vitro study of this compound in future.

[ta5]

TMG:

Neurol Sci. 2014 Feb 19.
Betaine suppressed Aβ generation by altering amyloid precursor protein processing.
Liu XP, Qian X, Xie Y, Qi Y, Peng MF, Zhan BC, Lou ZQ.
Betaine was an endogenous catabolite of choline, which could be isolated from vegetables and marine products. Betaine could promote the metabolism of homocysteine in healthy subjects and was used for hyperlipidemia, coronary atherosclerosis, and fatty liver in clinic. Recent findings shown that Betaine rescued neuronal damage due to homocysteine induced Alzheimer's disease (AD) like pathological cascade, including tau hyperphosphorylation and amyloid-β (Aβ) deposition. Aβ was derived from amyloid precursor protein (APP) processing, and was a triggering factor for AD pathological onset. Here, we demonstrated that Betaine reduced Aβ levels by altering APP processing in N2a cells stably expressing Swedish mutant of APP. Betaine increased α-secretase activity, but decreased β-secretase activity. Our data indicate that Betaine might play a protective role in Aβ production.
PMID: 24549986


J Neurochem. 2013 Feb;124(3):388-96.
Betaine attenuates Alzheimer-like pathological changes and memory deficits induced by homocysteine.
Chai GS1, Jiang X, Ni ZF, Ma ZW, Xie AJ, Cheng XS, Wang Q, Wang JZ, Liu GP.
Hyperhomocysteinemia (Hhcy) may induce memory deficits with β-amyloid (Aβ) accumulation and tau hyperphosphorylation. Simultaneous supplement of folate and vitamin B12 partially restored the plasma homocysteine level and attenuated tau hyperphosphorylation, Aβ accumulation and memory impairments induced by Hhcy. However, folate and vitamin B12 treatment have no effects on Hhcy which has the methylenetetrahydrofolate reductase genotype mutation. In this study, we investigated the effects of simultaneous supplement of betaine on Alzheimer-like pathological changes and memory deficits in hyperhomocysteinemic rats after a 2-week induction by vena caudalis injection of homocysteine (Hcy). We found that supplementation of betaine could ameliorate the Hcy-induced memory deficits, enhance long-term potentiation (LTP) and increase dendritic branches numbers and the density of the dendritic spines, with up-regulation of NR1, NR2A, synaptotagmin, synaptophysin, and phosphorylated synapsin I protein levels. Supplementation of betaine also attenuated the Hcy-induced tau hyperphosphorylation at multiple AD-related sites through activation protein phosphatase-2A (PP2A) with decreased inhibitory demethylated PP2A© at Leu309 and phosphorylated PP2A© at Tyr307. In addition, supplementation of betaine also decreased Aβ production with decreased presenilin-1 protein levels. Our data suggest that betaine could be a promising candidate for arresting Hcy-induced AD-like pathological changes and memory deficits.
PMID: 23157378

[blood]

This is interesting - the antidepressant citalopram appears to down-regulate production of proteins associated with Alzheimer's:

http://www.washingto...c5c0_story.html
 

Study: A common antidepressant may cut Alzheimers protein

... researchers gave citalopram to older mice with Alzheimers-like brain damage. The animals plaques didnt go away, but they quit growing and dramatically fewer new plaques formed compared with mice given sugar water, the research team reported in the journal Science Translational Medicine.

Next, the researchers gave a single dose of citalopram or a placebo to 23 healthy young adults, people who were neither depressed nor old enough to have brain plaques. Tests of the volunteers spinal fluid over the next day and a half showed their normal amyloid production dropped by 37 percent, the researchers reported.

It will take years of additional research to tell whether that translates into any protective effect. Citalopram and similar drugs called selective serotonin reuptake inhibitors, or SSRIs, alleviate depression by affecting levels of the brain chemical serotonin; Sheline said citalopram probably alters amyloid production in a completely different way.

In fact, the next question is whether its even possible to tamp amyloid production down for long periods or if the body would just get used to the drug and adjust. Sheline has begun enrolling healthy older adults to study the effect of using citalopram for two weeks.

Edited by blood, 23 May 2014 - 09:25 AM.

[Raptor87]

This is interesting - the antidepressant citalopram appears to down-regulate production of proteins associated with Alzheimer's:

http://www.washingto...c5c0_story.html
 

Study: A common antidepressant may cut Alzheimers protein

... researchers gave citalopram to older mice with Alzheimers-like brain damage. The animals plaques didnt go away, but they quit growing and dramatically fewer new plaques formed compared with mice given sugar water, the research team reported in the journal Science Translational Medicine.

Next, the researchers gave a single dose of citalopram or a placebo to 23 healthy young adults, people who were neither depressed nor old enough to have brain plaques. Tests of the volunteers spinal fluid over the next day and a half showed their normal amyloid production dropped by 37 percent, the researchers reported.

It will take years of additional research to tell whether that translates into any protective effect. Citalopram and similar drugs called selective serotonin reuptake inhibitors, or SSRIs, alleviate depression by affecting levels of the brain chemical serotonin; Sheline said citalopram probably alters amyloid production in a completely different way.

In fact, the next question is whether its even possible to tamp amyloid production down for long periods or if the body would just get used to the drug and adjust. Sheline has begun enrolling healthy older adults to study the effect of using citalopram for two weeks.

 

 

Too bad citalopram is a shitty drug, although it beats having alzheimers.

[niner]

 

Too bad citalopram is a shitty drug, although it beats having alzheimers.

 

Shitty because it's an SSRI, and they're shitty as a class, or particularly shitty in comparison to other SSRIs?  What exactly is wrong with it?