New rehabilitation strategies in patients with neurodegenerative disease

(understanding of brain plasticity mechanisms)

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Brain stimulation technique boosts language ability in Alzheimer's patientsImproved language performance in Alzheimer's disease following brain stimulation online firstA brain stimulation technique, known as repetitive transcranial magnetic stimulation, boosts the language ability of patients with Alzheimer's disease, suggests preliminary research, published online in the Journal of Neurology, Neurosurgery and Psychiatry.Repetitive transcranial magnetic stimulation, or rTMS for short, is a non-invasive technique that involves the delivery of a rapid succession of magnetic pulses in frequencies of up to 100 Hz.Previous research has shown that this can alter neuronal activity, depending on the frequency of the stimulation.The technique, which was applied to the prefrontal lobes for 25 minutes each time at a frequency of 20 Hz, was tested in 10 patients with moderate Alzheimer's disease.Half were randomly assigned to receive four weeks of rTMS (five days a week), and half were given a dummy treatment for two weeks, followed by two weeks of rTMS.Each participant was tested for memory, executive functions, such as planning, and language at the start of the study, then after two and four weeks, and again after eight weeks.Significant differences emerged between the two groups after two weeks in respect of the ability of participants to understand spoken language.The percentage of correct answers after a comprehension test rose from 66% to over 77% among those given rTMS, whereas there was no change in those given the dummy technique.There was no further change after four weeks, but the improvements were still evident at eight weeks. Read more: happynews.com

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Beetroot juice lowers risk of heart disease and strokes

You'll look a little bloodthirsty while slurping it down. But don't let that put you off beetroot juice - because it could save your life. The bright-red juice contains the chemical nitrate, which dramatically reduces blood pressure, cutting the risk of heart disease and strokes. Read more: dailymail.co.uk

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Memories are made

(an impact on the design of drugs for the treatment)

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New research led by the University of Leicester and published in a prestigious international scientific journal has revealed for the first time the mechanism by which memories are formed. The study in the Department of Cell Physiology and Pharmacology found one of the key proteins involved in the process of memory and learning. The breakthrough study has potential to impact drug design to treat Alzheimer's disease.
Professor Tobin said: "The work, which was done wholly at the University of Leicester, is focused on the mechanisms by which we form memories. We found one of the key proteins involved in the process of memory and learning. This protein is present in the part of the brain in which memories are stored. We have found that in order for any memory to be laid down this protein, called the M3-muscarinic receptor, has to be activated. We have also determined that this protein undergoes a very specific change during the formation of a memory - and that this change is an essential part of memory formation. In this regard our study reveals at least one of the molecular mechanisms that are operating in the brain when we form a memory and as such this represents a major break through in our understanding of how we lay down memories. This finding is not only interesting in its own right but has important clinical implications. One of the major symptoms of Alzheimer's disease is memory loss. Our study identifies one of the key processes involved in memory and learning and we state in the paper that drugs designed to target the protein identified in our study would be of benefit in treating Alzheimer's disease." Read more: ncbi.nlm.nih.gov

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Resveratrol may boost eye health

The vascular benefits of resveratrol – a compound found in red wine, blueberries and peanuts – may extend to reducing the risk of blindness for diabetics and seniors, says a new study. Read more: nutraingredients.com

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Nutritional status in Alzheimer's disease

(Could intake of vitamins C and E inhibit development of dementia)

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OBJECTIVE: To describe the nutritional status of elderly subjects with mild to moderate Alzheimer's disease. Of the total, 65% were female. More than 70% were capable of accomplishing daily activities by themselves. Subjects were eutrophic with a statistically significant difference of the arm circumference between the mild and moderate groups. As for illnesses secondary to Alzheimer's, 52% of the elderly presented hypertension, followed by arthrosis type alterations (17%). The mean consumption of energy and macronutrients in the elderly classified as mild dementia was of 1645 kcal, distributed in 53.7% of carbohydrate, 17.5% of proteins or 0.9 g/kg and 28.8% of lipids. For those classified as moderate dementia it was of 1482 kcal, distributed in 59.3% of carbohydrate, 16.1% of proteins and 24.6% of lipids.
CONCLUSION: In this descriptive study of elderly outpatients with mild and moderate Alzheimer's disease, most presented a nutritional status of eutrophy, with adequate dietary intake of carbohydrates, proteins, lipids and vitamin C, but with low dietary intake of vitamin E.
Oral supplementation of vitamin C (ascorbic acid) and vitamin E (D-alfa-tocopherol acetate) alone and in combination have been shown to decrease oxidative DNA damage in animal studies in vivo, in vitro, and in situ. Recent results of a prospective observational study (n = 4740) suggest that the combined use of vitamin E 400 IU daily and vitamin C 500 mg daily for at least 3 years was associated with the reduction of AD prevalence (OR 0.22; 95% CI 0.05 to 0.60) and incidence (HR 0.36; 95% CI 0.09 to 0.99). Contradicting this is a previous prospective observational study (n = 980) evaluating the relationship between 4 years of vitamin C and E intake and the incidence of AD, which detected no difference in the incidence of AD during the 4-year follow-up. Recent meta-analysis results suggest that doses of vitamin E > or =400 IU daily for more than one year are associated with increased all-cause mortality. Mega-trial results suggest that vitamin E doses > or =400 IU daily for 6.9 years in patients with preexisting vascular disease or diabetes mellitus increase the incidence of heart failure, with no other outcome benefits noted.
CONCLUSIONS: In the absence of prospective, randomized, controlled clinical trials documenting benefits that outweigh recently documented morbidity and mortality risks, vitamin E supplements should not be recommended for primary or secondary prevention of AD. Although the risks of taking high doses of vitamin C are lower than those with vitamin E, the lack of consistent efficacy data for vitamin C in preventing or treating AD should discourage its routine use for this purpose.  Read more: ncbi.nlm.nih.gov

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Study Connects Body Weight To Higher Alzheimer Risk

Corpulence is unhealthy! But under certain circumstances a few extra pounds can prove advantageous. People with a lower body mass index (BMI) face a greater risk of common age-related dementia progressing into Alzheimer's Disease or other forms of profound dementia.  Read more: medilexicon.com

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A better target for noninvasive imaging of Alzheimer's disease

( the first evidence for the existence of Alzheimer's-specific plaques in the retina )

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The nerve cell-damaging plaque that builds up in the brain with Alzheimer's disease also builds up in the retinas of the eyes - and it shows up there earlier, leading to the prospect that noninvasive optical imaging of the eyes could lead to earlier diagnosis, intervention and monitoring of the disease, according to new research. Scientists discovered characteristic amyloid plaques in retinas from deceased Alzheimer's disease patients and used a noninvasive optical imaging technique to detect retinal plaques in live laboratory mice genetically modified to model the human disease. The combined results suggest the possibility that noninvasive retinal imaging may be helpful in early diagnosis of the disease.
Noninvasive monitoring of β-amyloid (Aβ) plaques, the neuropathological hallmarks of Alzheimer's disease (AD), is critical for AD diagnosis and prognosis. Current visualization of Aβ plaques in brains of live patients and animal models is limited in specificity and resolution. The retina as an extension of the brain portrays an appealing target for a live, noninvasive optical imaging of AD if disease pathology is manifested there. We identified retinal Aβ plaques in postmortem eyes from AD patients (n = 8) and in suspected early stage cases (n = 5), consistent with brain pathology and clinical reports; plaques were undetectable in age-matched non-AD individuals (n = 5). In APP_SWE/PS1_∆E9 transgenic mice (AD-Tg; n = 18) and not in non-Tg wt mice (n = 10), retinal Aβ plaques were detected following systemic administration of curcumin, a safe plaque-labeling fluorochrome. Moreover, retinal plaques were detectable earlier than in the brain and accumulated with disease progression. An immune-based therapy effective in reducing brain plaques, significantly reduced retinal Aβ plaque burden in immunized versus non-immunized AD mice (n = 4 mice per group). In live AD-Tg mice (n = 24), systemic administration of curcumin allowed noninvasive optical imaging of retinal Aβ plaques in vivo with high resolution and specificity; plaques were undetectable in non-Tg wt mice (n = 11). Our discovery of Aβ specific plaques in retinas from AD patients, and the ability to noninvasively detect individual retinal plaques in live AD mice establish the basis for developing high resolution optical imaging for early AD diagnosis, prognosis assessment and response to therapies. Read more: sciencedirect.com

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Possible Environmental Causes For Alzheimer's

A new study by researchers at Rhode Island Hospital have found a substantial link between increased levels of nitrates in our environment and food, with increased deaths from diseases, including Alzheimer's. Read more: medicalnewstoday.com

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Alzheimer’s Disease: A PET Scan Showed Amyloid

( a PET scanner to directly see plaque in a living person’s brain )

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Ever since Alzheimer’s disease was described by a German doctor, Alois Alzheimer, in 1906, there was only one way to know for sure that a person had it. A pathologist, examining the brain after death, would see microscopic black freckles, plaque, sticking to brain slices like barnacles. Without plaque, a person with memory loss did not have the disease. There is no treatment yet to stop or slow the progress of Alzheimer’s. But every major drug company has new experimental drugs it hopes will work, particularly if they are started early. The questions though, are who should be getting the drugs and who really has Alzheimer’s or is developing it? Even at the best medical centers, doctors often are wrong. Twenty percent of people with dementia — a loss of memory and intellectual functions — who received a diagnosis of Alzheimer’s, did not have it. There was no plaque when their brains were biopsied. Half with milder memory loss, thought to be on their way to Alzheimer’s, do not get the disease. And with such a high rate of misdiagnosis, some who are mistakenly told that they have Alzheimer’s are not treated for conditions, like depression or low levels of thyroid hormone or drug side effects and interactions, that are causing their memory problems. Brain scans that showed plaque could help with some fundamental questions — who has or is getting Alzheimer’s, whether the disease ever stops or slows down on its own and even whether plaque is the main culprit causing brain cell death. Read more: nytimes.com

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Pine bark extract may ease hayfever symptoms

Daily supplements of an extract from the bark of the French maritime pine may ease symptoms of hay fever, says a new study.  Read more: nutraingredients.com

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The Latest News on Alzheimer’s Disease

( will soon begin )

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Summer has arrived, and the warm weather means a lot of good things have returned-- including another issue of Preserving Your Memory. We think you'll find that this issue has plenty of hopeful news and helpful information for Alzheimer's patients and caregivers alike.

We started a campaign "Stop Alzheimer's Now... It's in Your Hands," to raise funds for exciting new scientific research discoveries into Alzheimer's disease.  The scientists we fund are under the direction of Nobel laureate Dr. Paul Greengard.  Our scientists have made recent advances in their research that might lead to new treatments, and we now need to help fund it.  Now is the time!  The answer could be a dollar away.  100%, yes that means every dollar, until September 1st is going to groundbreaking Alzheimer's research from a Nobel Prize winning researcher.  In this exciting time, I hope that you will join us. www.ALZinfo.org/team. Read more: clicks.aweber.com

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Food ingredients are not pharmaceuticals

The president and chief executive officer of DSM Nutritional Products, Leendert Staal, says his company is facing up to life under EU’s new health claims rules, but has not changed its approach to nutrition science and product innovation.  Read more: nutraingredients.com

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Consequences of Brain Amyloidosis

( Mechanisms of Disease )

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"Neurodegenerative diseases have long been defined by the properties of the neuropathological lesions observed in the brain. We now know that these lesions are not just markers for neurodegenerative diseases, but are tied intrinsically to their pathogenesis. Moreover, the striking similarities between many neurodegenerative diseases suggest common mechanisms in the etiology of these disorders. The repeated theme of protein misfolding leading to amyloid formation and neurotoxicity is reinforced by a striking message from genetic studies: In each case of dominantly inherited neurodegeneration, the disease-causing mutations can be linked directly to amyloid formation. These clues have now come into sharp focus and neurodegenerative properties are better understood, and they have provided a strong rationale for the in vitro experiments, mouse models, and epidemiological studies that have gone a long way towards verifying this hypothesis. These experiments have laid a solid groundwork for a number of potential therapeutics that are now in preclinical and clinical development. Over the next five years the efficacy of a large number of these drugs will be tested, and there is a growing optimism that the results of these trials will confirm current notions of the etiology of neurodegenerative diseases". Read more: annualreviews.org

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 Hearing loss: not enough folate

Low blood levels of folate are associated with a 35 per cent increased risk of hearing loss, says a new study from Australia that strengthens the link between B vitamins and hearing. Read more: nutraingredients.com

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The future use of omega-3 fatty acid supplementation in the management or prevention of early AD

( to spur much needed research )

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Omega-3 fatty acids are essential for brain growth and development. They play an important role throughout life, as critical modulators of neuronal function and regulation of oxidative stress mechanisms, in brain health and disease. Docosahexanoic acid (DHA), the major omega-3 fatty acid found in neurons, has taken on a central role as a target for therapeutic intervention in Alzheimer’s disease (AD). A plethora of in vitro, animal model, and human data, gathered over the past decade, highlight the important role DHA may play in the development of a variety of neurological and psychiatric disorders, including AD. Cross sectional and prospective cohort data have demonstrated that reduced dietary intake or low brain levels of DHA are associated with accelerated cognitive decline or the development of incipient dementia, including AD. Several clinical trials investigating the effects of omega-3 fatty acid supplementation in AD have been completed and all failed to demonstrate its efficacy in the treatment of AD. However, these trials produced intriguing data suggesting that the beneficial effects of omega-3 fatty acid supplementation may depend on the stage of disease, other dietary mediators, and apolipoprotein E status.
These data suggest three emerging themes and possible areas of future exploration: 1) dependence of the potential beneficial effects of omega-3 PUFA on cognitive status, with cognitively normal persons and those in the earliest stages of memory decline (MCI or early AD) showing the greatest benefit; 2) a modulatory effect of dietary n-6 intake that alters the n-3/n-6 ratio and may negate the positive benefits of n-3 supplementation irrespective of n-3 intake; and 3) a potential modulatory role of ApoE status that influences the dietary benefits of omega-3 PUFA on cognition. Incomplete assessment of these potential modulators/confounders across studies prevents firm conclusions from being drawn. Read more: ncbi.nlm.nih.gov

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Omega-3 shows benefits against ‘oxidative stress’

The heart health benefits of omega-3 fatty acids EPA and DHA may be related to their ability to reduce oxidative stress, suggests new research. Read more: nutraingredients.com

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Protective Effect of Resveratrol on Neurodegeneration

( beneficial effects of resveratrol and grape polyphenols )

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Resveratrol is present in a variety of plants including vegetables, fruits, grains, roots, flowers, seeds, tea, and wine. It has been shown to offer protective effects against a number of cardiovascular and neurodegenerative diseases, and cancer. Although the mechanisms by which resveratrol exerts such a wide range of beneficial effects on these diseases have not yet been clearly elucidated, a number of studies have reported on its antioxidant, anti-inflammatory, and metal-chelating properties. Excess production of reactive oxygen species in the brain has been implicated as a common underlying risk factor for the pathogenesis of a number of neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), and stroke. In recent years, there is considerable interest concerning investigation of antioxidative and anti-inflammatory effects of phenolic compounds from different botanical sources. In this review, we first describe oxidative mechanisms associated with stroke, AD, and PD, and subsequently, we place emphasis on recent studies implicating neuroprotective effects of resveratrol, a polyphenolic compound derived from grapes and red wine. These studies show that the beneficial effects of resveratrol are not only limited to its antioxidant and anti-inflammatory action but also include activation of sirtuin 1 (SIRT1) and vitagenes, which can prevent the deleterious effects triggered by oxidative stress. In fact, SIRT1 activation by resveratrol is gaining importance in the development of innovative treatment strategies for stroke and other neurodegenerative disorders. The goal here is to provide a better understanding of the mode of action of resveratrol and its possible use as a potential therapeutic agent to ameliorate stroke damage as well as other age-related neurodegenerative disorders. Read more: springerlink.com

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The ignited flames of hope for an anti-ageing pill

Resveratrol – a compound in red wine - may be influencing both blood vessel function and the function of fat cells, say new studies which may help explain its heart health benefits. Read more: nutraingredients.com

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Complete Phenotypic Recovery of an Alzheimer's Disease Model

( the development of novel amyloid aggregation inhibitors of high potency )

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The rational design of amyloid oligomer inhibitors is yet an unmet drug development need. Previous studies have identified the role of tryptophan in amyloid recognition, association and inhibition. Furthermore, tryptophan was ranked as the residue with highest amyloidogenic propensity. Other studies have demonstrated that quinones, specifically anthraquinones, can serve as aggregation inhibitors probably due to the dipole interaction of the quinonic ring with aromatic recognition sites within the amyloidogenic proteins. Here, using in vitro, in vivo and in silico tools we describe the synthesis and functional characterization of a rationally designed inhibitor of the Alzheimer's disease-associated beta-amyloid. This compound, 1,4-naphthoquinon-2-yl-L-tryptophan (NQTrp), combines the recognition capacities of both quinone and tryptophan moieties and completely inhibited Abeta oligomerization and fibrillization, as well as the cytotoxic effect of Abeta oligomers towards cultured neuronal cell line. Furthermore, when fed to transgenic Alzheimer's disease Drosophila model it prolonged their life span and completely abolished their defective locomotion. Analysis of the brains of these flies showed a significant reduction in oligomeric species of Abeta while immuno-staining of the 3(rd) instar larval brains showed a significant reduction in Abeta accumulation. Computational studies, as well as NMR and CD spectroscopy provide mechanistic insight into the activity of the compound which is most likely mediated by clamping of the aromatic recognition interface in the central segment of Abeta. Our results demonstrate that interfering with the aromatic core of amyloidogenic peptides is a promising approach for inhibiting various pathogenic species associated with amyloidogenic diseases. The compound NQTrp can serve as a lead for developing a new class of disease modifying drugs for Alzheimer's disease. Read more:  ncbi.nlm.nih.gov

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Tea and coffee support heart health

Between three and six cups of tea a day may reduce the risk of death from heart disease by about 45 per cent, says a new study from The Netherlands.  Read more: nutraingredients.com

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 Changes from normal aging to preclinical Alzheimer's disease

( Treatment Options )

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Impaired memory is typically one of the first signs of Alzheimer's disease, but difficulty recalling the names of friends or recent events is also common among normal elderly persons. The clinician is thus faced with the difficulty of distinguishing between normal aging and the early stages of Alzheimer's disease. Mild cognitive impairment is an intermediate state in which persons have more memory problems than would be considered normal for their age, but their symptoms are not as severe as the symptoms of Alzheimer disease and they do not have functional impairment. Alzheimer's disease develops at a much higher frequency among persons with mild cognitive impairment than among those with normal aging. Determining when patients have reached the very early stage of Alzheimer's disease is not easy, particularly because it is likely that a preclinical stage of Alzheimer's disease exists in which senile plaques, neuritic plaques, and neurofibrillary tangles occur in sufficient numbers to meet standard neuropathological criteria for Alzheimer's disease in the absence of overt symptoms or signs of dementia. Other causes of memory impairment must also be considered, such as cerebrovascular disease, hydrocephalus, hypothyroidism, vitamin B12 deficiency, central nervous system infection, a cognitive disorder related to human immunodeficiency virus infection, adverse effects of prescribed medications, substance abuse, and cancer. Read more:  content.nejm.org

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Herbal remedies can treat ailments

Eating when your stomach is upset may seem like a bad idea, but some foods can actually help with nausea. Read more: livepdx.com

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Side Effect Of Alzheimer's Drugs Is Unlikely

( blood testing may not be the best way to monitor amyloid beta )

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The first trial of a new model for testing Alzheimer's treatments has reassured researchers that a promising class of drugs does not exacerbate the disease if treatment is interrupted. Scientists at Washington University School of Medicine in St. Louis and Merck & Co. Inc studied the effects of a class of drugs known as gamma secretase inhibitors. Researchers had worried that these drugs might cause a build-up of proteins linked to Alzheimer's disease and that this build-up could be unleashed in a surge when patients went off the medications. But the new study suggests that they do not. "This is important because it eases some concerns that have been raised about this potentially useful class of medications," says senior author Randall Bateman, MD, a Washington University neurologist who treats patients at Barnes-Jewish Hospital. The findings appeared recently in The Journal of Neuroscience.
Gamma secretase inhibitors block proteins involved in the creation of amyloid beta, the main ingredient of Alzheimer's plaques. Patients cannot continuously take these drugs because nonstop inhibition of the gamma secretase enzyme has harmful side effects. One study had revealed that when physicians temporarily halted used of the inhibitors in humans, amyloid beta levels in the blood surged. An animal study suggested cessation of treatment also led to an amyloid beta increase in the brain. Researchers have been watching for similar effects in current human clinical trials of gamma secretase inhibitors. Read more:  redorbit.com

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In delaying the onset and progression of AD

A pilot study was conducted on 21 residents with moderate-to-late-stage Alzheimer's at two Massachusetts nursing homes. Participating residents drank two to four glasses of apple juicy a day for one month. While they demonstrated no change in the Dementia Rating Scale, caregivers reported an approximate 27% improvement in behavioral and psychotic symptoms associated with dementia. The largest changes occurred in anxiety, agitation and delusion. Read more: mcknights.com

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