Alzheimer's Disease

Pilot drug studies

Older news items (pre-2010) brought over from the old website

Tarenflurbil fails clinical trial

In another example of a drug that worked in mice but failed to show a benefit for patients, a study has found that the drug tarenflurbil, which supposedly suppresses the accumulation of amyloid plaque—did not slow cognitive decline or loss of usual daily activities (and was moreover associated with adverse effects including anemia, pneumonia, and herpes zoster). Although the drug showed promise in a small clinical trial, the results were negative in this larger, randomized trial, involving 1684 patients with mild Alzheimer’s. It’s suggested that rather than focusing on Alzheimer's disease and its specific characteristics, we should see dementia as a confluence of three common disease processes—Alzheimer's disease, vascular brain injury, and Lewy body disease.

Jonsson, M., Edman, Å., Lind, K., Rolstad, S., Sjögren, M., & Wallin, A. (2009). Apathy is a prominent neuropsychiatric feature of radiological white-matter changes in patients with dementia. International Journal of Geriatric Psychiatry, 9999(9999), n/a. doi: 10.1002/gps.2379.

http://www.eurekalert.org/pub_releases/2009-12/ghcc-jet121109.php

Neurogenesis improved in Alzheimer mice

Studies of adult neurogenesis in genetically engineered mice have revealed two main reasons why amyloid-beta peptides and apolipoprotein E4 impair neurogenesis, and identified drug treatments that can fix it. The findings point to a deficit in GABAergic neurotransmission or an imbalance between GABAergic and glutamatergic neurotransmission as an important contributor to impaired neurogenesis in Alzheimer’s. While stem cell therapy for Alzheimer’s is still a long way off, these findings are a big step toward that goal.

Gang Li et al. 2009. GABAergic Interneuron Dysfunction Impairs Hippocampal Neurogenesis in Adult Apolipoprotein E4 Knockin Mice. Cell Stem Cell, 5 (6), 634-645.

Binggui Sun et al. 2009. Imbalance between GABAergic and Glutamatergic Transmission Impairs Adult Neurogenesis in an Animal Model of Alzheimer's Disease. Cell Stem Cell, 5 (6), 624-633.

http://www.eurekalert.org/pub_releases/2009-12/gi-gsi113009.php

Protein identified that counterbalances Alzheimer's proteins

A mouse study has revealed that a protein called Reelin may provide a new approach to tackling Alzheimer’s. Reelin activates and strengthens the response of the NMDA receptor, which plays an important role in coordinating chemical signals between adjacent nerve cells. In the presence of too much amyloid-beta protein (as occurs in an Alzheimer’s brain), the receptor migrates into the cell, reducing the cell's sensitivity to incoming signals. However, with strong concentrations of Reelin, the receptor remains active and the cell continues receiving normally. The findings also make a connection with ApoE4 — the receptor that binds to ApoE also binds to Reelin, and is part of the complex that controls the sensitivity of the NMDA receptors.

Durakoglugil, M. S., Chen, Y., White, C. L., Kavalali, E. T., & Herz, J. (2009). Reelin signaling antagonizes β-amyloid at the synapse. Proceedings of the National Academy of Sciences, 106(37), 15938-15943. doi: 10.1073/pnas.0908176106.

http://www.eurekalert.org/pub_releases/2009-10/usmc-nfa100609.php

Epilepsy drug may help Alzheimer's patients

A study involving genetically engineered mice has found that mice given the anti-seizure drug valproic acid soon after onset of the disease showed improved memory and reduced plaques. The acid worked by blocking the cascade of reactions that leads to beta-amyloid plaques. Valproic acid helped mice less as their disease progressed.

Qing, H. et al. 2008. Valproic acid inhibits Aβ production, neuritic plaque formation, and behavioral deficits in Alzheimer's disease mouse models. The Journal of Experimental Medicine, Published online October 27.

http://www.eurekalert.org/pub_releases/2008-10/rup-edm102008.php

New drug for Alzheimer’s

A pilot study of 321 people with mild and moderate Alzheimer's disease has found that those who took the new drug Rember for 50 weeks demonstrated a dramatically smaller reduction (81%) in mental decline compared with those on the placebo. Those on rember did not experience a significant decline in their mental function over 19 months, while those on a placebo got worse. Rember is the first drug to act on the tau protein. A "phase 3" trial is planned for next year, involving a larger group of people with the disease, and if that is successful, the drug could be available by 2012.

The findings were presented at the international conference on Alzheimer's disease in Chicago.

http://www.guardian.co.uk/science/2008/jul/30/medicalresearch.health

Early study reveals new drug could improve executive function in Alzheimer's patients

A trial of a new drug called PBT2 has been found to improve two indicators of executive function in patients with Alzheimer's disease, and reduces levels of amyloid β in the cerebrospinal fluid. There was no significant effect on memory, but this could be because memory functions deteriorate more slowly than executive ones during the early stage, making changes harder to detect in such a short study. The parent compound to PBT2 is clioquinol.

Lannfelt, L. et al. 2008. Safety, efficacy, and biomarker findings of PBT2 in targeting Aβ as a modifying therapy for Alzheimer's disease: a phase IIa, double-blind, randomised, placebo-controlled trial. The Lancet Neurology, 7 (9), 779-786.

http://www.eurekalert.org/pub_releases/2008-07/l-esr072808.php
http://www.eurekalert.org/pub_releases/2008-07/icl-adp072908.php

Dimebon significantly improves Alzheimer's symptoms

A study involving 183 Russian patients with mild-to-moderate Alzheimer’s has found that a drug previously used as an antihistamine (dimebon) significantly improved cognitive performance. Moreover, it demonstrated increasing benefits over 12 months, which no currently approved therapies do.

Doody, R.S. et al. 2008. Effect of dimebon on cognition, activities of daily living, behaviour, and global function in patients with mild-to-moderate Alzheimer's disease: a randomised, double-blind, placebo-controlled study. The Lancet, 372 (9634), 207-215.

http://www.eurekalert.org/pub_releases/2008-07/l-dsi071608.php

Tarenflurbil slows decline of mild Alzheimer's patients

A trial of 210 patients with mild to moderate Alzheimer’s has found that those with mild Alzheimer’s who received 800mg of tarenflurbil twice a day for a year experienced a rate of decline 46% lower than placebo patients in the activities of daily living scale, and a 36% reduction in the pace of decline in global function.  In those with moderate Alzheimer’s, neither 400mg or 800mg of tarenflurbil had a significant effect, and indeed impacted negatively on a third measure of global function. Patients with mild Alzheimer’s who took 800mg for 24 months had lower rates of decline for all three primary outcomes than those who took it for a shorter period.

Wilcock, G.K. et al. 2008. Efficacy and safety of tarenflurbil in mild to moderate Alzheimer's disease: a randomised phase II trial. Lancet Neurology, 7, 483-493.

http://www.eurekalert.org/pub_releases/2008-04/l-tsd042808.php

Potential new drug target identified

A mouse study has successfully reduced the production of beta-amyloid peptides, and improved memory. These peptides are produced when enzymes cut APP at two places, called the beta-secretase and gamma-secretase sites. Previous research has focused on a mutant beta-secretase sequence only seen in one extended family of patients, the so-called Swedish mutation. The new study identifies a different enzyme, called Cathepsin B (CatB), which works to cut the normal beta-secretase site in more than 99% of patients with Alzheimer’s. Two compounds that inhibit CatB were successfully tested, producing great improvement in memory, as well as reduced brain levels of beta amyloid.

Hook, V.Y.H., Kindy, M. & Hook, G. 2008. Inhibitors of Cathepsin B Improve Memory and Reduce β-Amyloid in Transgenic Alzheimer Disease Mice Expressing the Wild-type, but Not the Swedish Mutant, β-Secretase Site of the Amyloid Precursor Protein. Journal of Biological Chemistry, 283, 7745-7753.

http://www.eurekalert.org/pub_releases/2008-03/uoc--pad031108.php

PLMI factor in sleep disturbance for dementia patients

A study of 102 people diagnosed with both cognitive impairment and sleep disturbance (average nightly sleep of seven or less hours and daytime sleep of 30 minutes or longer) found that periodic leg movement disorder (a condition that causes people to jerk and kick their legs every 20 to 40 seconds during sleep) was predictive of reduced total sleep time in older adults with Alzheimer disease and related dementias. Given that sleep disturbance in persons with dementia is a highly prevalent and disabling symptom, and sedative-hypnotics are not recommended, this finding is important because it suggests treatment of periodic leg movements may be beneficial.

Richards, K.C. et al. 2008. Periodic Leg Movements Predict Total Sleep Time in Persons with Cognitive Impairment and Sleep Disturbance. SLEEP, 31(2), 224-230.

http://www.eurekalert.org/pub_releases/2008-02/aaos-ppt012808.php

Reduction of tau protein protects against Alzheimer’s

A study using genetically engineered mice has found that when tau protein was reduced their memory function was retained and they lived a normal lifespan, even though amyloid-beta levels weren’t affected. They were also made mice more resistant to epileptic seizures.

Roberson, E.D. et al. 2007. Reducing Endogenous Tau Ameliorates Amyloid ß-Induced Deficits in an Alzheimer's Disease Mouse Model. Science, 316 (5825), 750-754.

http://www.eurekalert.org/pub_releases/2007-05/gi-sin042707.php

Marijuana may slow progression of Alzheimer's disease

New evidence suggests that marijuana — which has strong anti-inflammatory effects — may contain compounds that slow the memory loss associated with Alzheimer's disease. Treatment with a synthetic compound similar to marijuana (WIN-55212-2) reduced inflammation in older rats and substantially improved their memories.

The researchers presented their findings October 18 at the annual Society for Neuroscience meeting in Atlanta.

http://www.eurekalert.org/pub_releases/2006-10/osu-lb101206.php
http://www.sciencedaily.com/releases/2006/10/061018151055.htm

New drug reduces plaque and tangles in Alzheimer's mice

Alzheimer's mice that received a compound known as AF267B for eight weeks performed significantly better on a spatial memory test than untreated mice did. A different memory test that involved associating a place with a shock was not affected. The drug was found to reduce plaques and tangles in the hippocampus but not in the amygdala. AF267B seems to work in part by enhancing the activity of receptors for the neurotransmitter acetylcholine, and boosting the levels of an enzyme called alpha secretase, which blocks the production of beta-amyloid proteins. Suppressing the M1 receptors worsened the condition and performance of Alzheimer’s mice, confirming the important role of M1 receptors in modulating the plaques and tangles characteristic of Alzheimer’s.

Caccamo, A. et al. 2006. M1 Receptors Play a Central Role in Modulating AD-like Pathology in Transgenic Mice. Neuron, 49, 671-682.

http://www.scientificamerican.com/article.cfm?id=drug-found-to-reverse-the

New compound stops brain cell degeneration in Alzheimer's disease

A new orally administered compound specifically targeted to suppress brain cell inflammation and neuron loss associated with Alzheimer's disease has been developed. The compound, MW01-5-188WH, is rapidly absorbed by the brain and is non-toxic. It selectively inhibits production of pro-inflammatory proteins called cytokines by glia, giving it relevance for several neurodegenerative disorders. The compound suppressed brain inflammation and neuron dysfunction in the hippocampus and protected against cognitive decline in genetically engineered mice. The compound also restored normal levels of markers of synaptic dysfunction in the hippocampus and attenuated Alzheimer's-like behavioral deficits. The compound represents a new approach to Alzheimer’s therapy.

Ranaivo, H.R., Craft, J.M., Hu, W., Guo, L., Wing, L.K., Van Eldik, L.J. & Watterson, D.M. 2006. Glia as a Therapeutic Target: Selective Suppression of Human Amyloid-Induced Upregulation of Brain Proinflammatory Cytokine Production Attenuates Neurodegeneration. Journal of Neuroscience, 26, 662-670.

http://www.eurekalert.org/pub_releases/2006-01/nu-ncs011906.php

Testosterone improves quality of life

A 24-week study involving 16 male patients diagnosed with mild Alzheimer disease and 22 healthy male controls found that Alzheimer’s patients who received daily testosterone treatment showed significant improvement on a quality-of-life instrument that encompasses memory, interpersonal relationships, physical health, energy, living situation and overall well-being, however improvement in memory or other cognitive skills using cognitive tests did not reach significance. Among healthy controls, those receiving testosterone showed a non-significant trend toward greater improvement in self-rated quality of life.

Lu, P.H. et al. 2006. Effects of Testosterone on Cognition and Mood in Male Patients With Mild Alzheimer Disease and Healthy Elderly Men. Archives of Neurology, 63.
Full text at http://archneur.ama-assn.org/cgi/content/full/63.2.nct50002v1

http://www.eurekalert.org/pub_releases/2005-12/uoc--apt120805.php

Natural compound from 'pond scum' shows potential activity against Alzheimer's

A compound isolated from a cyanobacterium, a type of blue-green algae (‘pond scum’) shows promise of becoming a natural drug candidate for fighting Alzheimer's. Nostocarboline (the newly isolated compound) is a potent inhibitor of cholinesterase, with a potency comparable to galanthamine.

Becher, P.G., Beuchat, J., Gademann, K. & Jüttner, F. 2005. Nostocarboline: Isolation and Synthesis of a New Cholinesterase Inhibitor from Nostoc 78-12A. Journal of Natural Product, 68(12), 1793–1795.

http://www.eurekalert.org/pub_releases/2005-12/acs-ncf122705.php

Gas-blockers might slow down Alzheimer's disease

Beta-amyloid is known to cause brain cells to make an inhibitor of an enzyme that triggers the production of nitric oxide (iNOS). This enzyme is normally turned on during infection and is needed to help immune cells destroy invading pathogens, but it is not normally found in the brain, where it may cause cellular damage that destroys neurons. Although it’s long been known that iNOS is present in the brain lesions of Alzheimer’s patients, it hasn’t been known whether its presence makes things worse. A new study has now shown that Alzheimer's-prone mice that lack iNOS live twice as long and develop fewer brain lesions than iNOS-expressing mice. The researchers suggest that iNOS inhibitors might turn out to be an effective in slowing the progression of Alzheimer's disease.

Nathan, C. et al. 2005. Protection from Alzheimer's-like disease in the mouse by genetic ablation of inducible nitric oxide synthase. Journal of Experimental Medicine, 202, 1163-1169.

http://www.eurekalert.org/pub_releases/2005-10/joem-gms102005.php

New memory drug works best in combination with older drug

An experimental drug – a compound known as SGS742 – has been successful in animal studies in improving memory, and is now in human clinical trials. The drug works by blocking certain chemicals that interfere with memory formation, thus enabling better acquisition and retention of new information. It alters the activity of gene control machinery that is important for memory consolidation. It was most effective when used in conjunction with Aricept, an established Alzheimer’s drug.

Helm, K.A., Haberman, R.P., Dean, S.L., Hoyt, E.C., Melcher, T., Lund, P.K. & Gallagher, M. 2005. GABAB receptor antagonist SGS742 improves spatial memory and reduces protein binding to the cAMP response element (CRE) in the hippocampus. Neuropharmacology, 48(7), 956-64.

http://www.eurekalert.org/pub_releases/2005-06/jhu-nmd060905.php

Chemical decoy shows promise for slowing Alzheimer's

A chemical polymer shows promise in cell culture studies of slowing Alzheimer’s by blocking the toxic brain proteins thought to cause the disease. The likely candidate for any drugs developed from this approach would be people at increased risk of Alzheimer’s, who haven’t yet developed signs of the disease.

Good, T. & Patel, D. 2005. BIOT 421 Development of biomimetic materials for Alzheimer's disease. Presented at 2:05 p.m., Thursday, March 17, at the Convention Center, Room 31A, during the "Tissue Engineering/Biomaterials" symposium at the 229th national meeting of the American Chemical Society.

http://www.eurekalert.org/pub_releases/2005-03/acs-ds030705.php

Antibody treatment partially reverses nerve damage in Alzheimer disease

A mouse study has had success in significantly decreasing structural nerve damage in the brains of mice with Alzheimer’s, by administering an beta amyloid antibody treatment to the brain surface.

Brendza, R.P. et al. 2005. Anti-Aß antibody treatment promotes the rapid recovery of amyloid-associated neuritic dystrophy in PDAPP transgenic mice.Journal of Clinical Investigation, 115, 428-433.

http://www.eurekalert.org/pub_releases/2005-01/joci-atp011305.php
http://news.bbc.co.uk/go/pr/fr/-/1/hi/health/4188677.stm

Rolipram - a potential new treatment

In a mouse study, a phosphodiesterase 4 inhibitor, rolipram, was found to improve memory in both long-term potential and contextual learning. Rolipram's protective effect is due to its ability to modify gene expression, making brain synapses more resistant to the insult caused by the accumulation of Ab. The beneficial effect of rolipram treatment was found to extend for at least 2 months after the end of one course of the treatment, and was more effective in the later stages of the disease.

Gong, B., Vitolo, O.V., Trinchese, F., Liu, S., Shelanski, M. & Arancio, O. 2004. Persistent improvement in synaptic and cognitive functions in an Alzheimer mouse model after rolipram treatment. Journal of Clinical Investigation, 114, 1624-1634.

http://www.eurekalert.org/pub_releases/2004-12/joci-r-a111804.php

Keeping blood pressure & cholesterol low may help some dementia patients more than Alzheimer's drugs

A comprehensive review of all recent medical studies on mixed dementia, vascular dementia and Alzheimer's suggests that efforts to treat cardiovascular risk factors, especially high blood pressure, may be more effective for many than memory drugs in protecting brain function.

Langa, K.M., Foster, N.L. & Larson, E.B. 2004. Mixed Dementia: Emerging Concepts and Therapeutic Implications. JAMA, 292, 2901-2908.

http://www.eurekalert.org/pub_releases/2004-12/uomh-thy120904.php

New type of Alzheimer's drug on trial

A clinical trial is commencing to test the effectiveness of a new type of drug, called Alzhemed, that attacks amyloid. The trial will last 18 months and will enroll about 950 Alzheimer's patients with a mild-to-moderate form of the disease, from centers around the United States and Canada. The drug actually physically combines with amyloid to prevent plaque formation, and is also expected to inhibit the inflammatory response associated with amyloid buildup in Alzheimer's.

http://www.eurekalert.org/pub_releases/2004-11/tju-jns110204.php

Blood pressure drugs may slow deterioration of Alzheimer's

A study involving 162 people in Japan living in long-term care facilities with mild to moderate Alzheimer's disease and high blood pressure has found that certain blood pressure drugs may slow the deterioration of Alzheimer's disease. The results, while interesting, will need to be replicated in carefully controlled, randomized, blinded studies.

Ohrui, T., Tomita, N., Sato-Nakagawa, T., Matsui, T., Maruyama, M., Niwa, K., Arai, H. & Sasaki, H. 2004. Effects of brain-penetrating ACE inhibitors on Alzheimer disease progression. Neurology, 63, 1324-1325.

http://www.eurekalert.org/pub_releases/2004-10/aaon-bpd100404.php

Anti-cholesterol drug treats Alzheimer's disease in mice

A drug that jams a key enzyme regulating cholesterol (CP-113,818) has been found to drastically reduce the levels of amyloid plaque in genetically engineered mice. The drug has not been tested in clinical trials, but another ACAT inhibitor, avasimibe, is now in final clinical trials as a treatment for vascular disease and atherosclerosis.

Hutter-Paier, B., Huttunen, H.J., Puglielli, L., Eckman, C.B., Kim, D.Y., Hofmeister, A., Moir, R.D., Domnitz, S.B., Frosch, M.P., Windisch, M. & Kovacs, D.M. 2004. The ACAT Inhibitor CP-113,818 Markedly Reduces Amyloid Pathology in a Mouse Model of Alzheimer's Disease. Neuron, 44 (2), 227–238.

http://www.eurekalert.org/pub_releases/2004-10/cp-adt101204.php

Protein found that dissolves amyloid fibers

Amyloid plaque is extremely tough — so tough researchers have been unable to find a means to attack them. A new study suggests that yeast may be the means. Oddly, the yeast protein seems to be involved both in making amyloid fibers, and in dissolving them. The yeast protein Sup35 sometimes forms amyloid fibers in yeast cells — this is part of the cell's normal biology, changing the types of proteins that the cell makes. Another protein — Hsp104 — appears to affect Sup35's ability to form amyloid fibers. When a yeast cell contained either high amounts of Hsp104 or none at all, amyloid fibers never formed. But when Hsp104 levels were small, the fibers flourished. In the latest study, researchers found that small amounts of Hsp104 catalyzed the formation of amyloid fibers, but large levels of the protein actually caused the fibers to dissolve. Interestingly, Hsp104 belongs to a class of proteins that sometimes are influenced by environmental factors.

Shorter, J., & Lindquist, S. (2004). Hsp104 Catalyzes Formation and Elimination of Self-Replicating Sup35 Prion Conformers. Science, 304(5678), 1793–1797. doi:10.1126/science.1098007

http://www.eurekalert.org/pub_releases/2004-05/wifb-rdp052004.php

Clioquinol slowed progression of cognitive decline in Alzheimer's patients

A new clinical trial has found that the drug Clioquinol slowed the progression of cognitive decline in a group of 36 patients with moderate to severe Alzheimer’s, over a period of 24 weeks. PBT-1 (Clioquinol) is a chemical that binds zinc and copper, and has been shown to lower the levels of beta-amyloid and the associated toxicity in the brains of transgenic mice used as a model of Alzheimer's disease.

Ritchie, C.W. et al. 2003. Metal-Protein Attenuation With Iodochlorhydroxyquin (Clioquinol) Targeting A β Amyloid Deposition and Toxicity in Alzheimer Disease: A Pilot Phase 2 Clinical Trial. Archives of Neurology, 60, 1685-1691.

http://www.eurekalert.org/pub_releases/2003-12/aaft-cto121503.php

Cancer drug may help against Alzheimer's too

The drug Gleevec, approved for treatment of chronic myelogenous leukemia (CML) over two years ago, has been found to reduce the level of beta-amyloid in immature rat neurons and cultured human cells. The drug also significantly reduced the levels of amyloid peptides in live guinea pigs (who have amyloid peptides comparable to those found in humans). While still preliminary, the work may indicate a new approach to treating Alzheimer’s.

Netzer, W.J. et al. 2003. Gleevec inhibits β-amyloid production but not Notch cleavage. PNAS, 100, 12444-12449.

http://www.scientificamerican.com/article.cfm?id=cancer-drug-may-help-figh

New Drug for Moderate-to-Severe Alzheimer's

Four drugs — donepezil, galantamine, rivastigmine, and tacrine — are approved for treatment of mild-to-moderate Alzheimer's disease in the U.S., but there are no approved treatments for severe AD. Now an industry-sponsored study has examined memantine for this use. The study involved 252 patients with moderate-to-severe AD, over a period of 28 weeks. Patients were evaluated on 7 tests of cognition, functional capacity, and behavior. Outcomes were significantly better with memantine than with placebo on 4 of these scales, and no significant adverse events were noted. It is not clear yet how clinically meaningful these small improvements are. Memantine has been approved for use in Europe.

Reisberg, B., Doody, R., Stöffler, A., Schmitt, F., Ferris, S. & Möbius, H.J. 2003. Memantine in moderate-to-severe Alzheimer's disease. New England Journal of Medicine, 348, 1333-41.

http://www.eurekalert.org/pub_releases/2003-04/nyum-dsp032603.php

DHEA supplement shows no effect on Alzheimer's

The supplement dehydroepiandrosterone, or DHEA, had no effect on Alzheimer's patients who took the supplement for six months. A transient benefit on cognitive performance occurred at three months, but was not statistically significant. Of the 58 people who started the study, 46 completed three months of treatment and 33 completed six months of treatment. The small size of the study and the high number of people who dropped out may limit the findings of the study.

Wolkowitz, O.M., Kramer, J.H., Reus, V.I., Costa, M.M., Yaffe, K., Walton, P., Raskind, M., Peskind, E., Newhouse, P., Sack, D., De Souza, E., Sadowsky, C., Roberts, E. & the DHEA-Alzheimer’s Disease Collaborative Research Group. 2003. DHEA treatment of Alzheimer’s disease: A randomized, double-blind, placebo-controlled study. Neurology, 60, 1071-1076.

http://www.eurekalert.org/pub_releases/2003-04/aaon-dss033103.php

Designer chemical offers Alzheimer's hope

Researchers at the University of Illinois at Chicago have designed and synthesized highly potent inhibitor compounds that could lead to an effective treatment for Alzheimer’s disease. In earlier work, the researchers had designed an inhibitor that blocks the action of one of two enzymes thought to be responsible for Alzheimer’s disease. This enzyme, called memapsin 2, is responsible for producing beta-amyloid, which forms the plaques so characteristic of Alzheimer’s disease. The inhibitor was reported in the Journal of the American Chemical Society last year and was shown to be effective in test tube experiments. However, while useful as a model, the inhibitor was too big to be effective in drug therapy. What is needed is a compound small enough to cross the blood-brain barrier. This latest paper reports on a new, smaller, generation of inhibitors designed and tested in the laboratory.

Golestani, N., Molko, N., Dehaene, S., LeBihan, D., & Pallier, C. (2007). Brain Structure Predicts the Learning of Foreign Speech Sounds. Cereb. Cortex, 17(3), 575–582. doi:10.1093/cercor/bhk001

http://www.eurekalert.org/pub_releases/2001-08/uoia-dco080201.php

Naturally occurring protein could slow Alzheimer's disease

A cholesterol-lowering protein produced by the body, Apolipoprotein A-1, might be able to slow the progression of Alzheimer's disease.
Everyone has some quantity of Apo-A, in their body. It is produced in the small intestine and the liver and is known to help prevent coronary heart disease. At normal levels, the protein clears cholesterol throughout the body, including in the brain. The scientists speculate that boosting Apo-A levels may also help clear beta amyloid, an important part of the Alzheimer's disease plaques that strangle normal brain cells. Further testing is needed to confirm the role of Apo-A in animals and its relation with Alzheimer's, before any human trials could begin.

Koldamova, R. P., Lefterov, I. M., Lefterova, M. I., & Lazo, J. S. (2001). Apolipoprotein A-I Directly Interacts with Amyloid Precursor Protein and Inhibits Aβ Aggregation and Toxicity†. Biochemistry, 40(12), 3553–3560. doi:10.1021/bi002186k

http://www.eurekalert.org/pub_releases/2001-04/ACS-Nopc-0104101.php

Why Vitamin E might slow the progress of Alzheimer's

A chemical called methionine (an amino acid found in beta-amyloid) may be the source of the toxic free radicals produced by the amyloid-beta peptide. Recent studies have demonstrated that higher than normal doses of vitamin E may slow the advance of Alzheimer's in some people with late stages of the disease. The current study provides a possible explanation for this link. Vitamin E, an antioxidant, appears to work by destroying free radicals (oxidants) produced by amyloid.

The study was presented at the 2000 International Chemical Congress of Pacific Basin Societies.

http://www.eurekalert.org/pub_releases/2000-12/ACS-Ript-1712100.php

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Diet & supplements for Alzheimer's

Older news items (pre-2010) brought over from the old website

Caffeine reverses memory impairment in Alzheimer's mice

Consistent with earlier indications that moderate caffeine consumption may protect against memory decline, a study of genetically engineered mice has found that when the old mice began to show memory impairment, those given caffeine for 2 months performed as well as normal aged mice on cognitive tests, while those given plain drinking water continued to do poorly. The Alzheimer's mice received the equivalent of five 8-oz. cups of regular coffee a day (or two cups of Starbucks coffee, or 14 cups of tea). Moreover, the brains of the caffeinated mice showed nearly a 50% reduction in levels of beta amyloid. The effect appears to be through suppression of both β-secretase and presenilin 1 /g-secretase expression. Caffeine had this effect only on those with Alzheimer’s; normal mice given caffeine through adulthood showed no cognitive benefit.

Arendash, G.W. et al. 2009. Caffeine Reverses Cognitive Impairment and Decreases Brain Amyloid-β Levels in Aged Alzheimer's Disease Mice. Journal of Alzheimer's Disease, 17 (3), 661-680.

Cao, C. et al. 2009. Caffeine Suppresses Amyloid-β Levels in Plasma and Brain of Alzheimer's Disease Transgenic Mice. Journal of Alzheimer's Disease, 17 (3), 681-697.

http://www.eurekalert.org/pub_releases/2009-07/uosf-crm070109.php

Vitamin B3 reduces Alzheimer's symptoms, lesions

High doses of nicotinamide, a form of vitamin B3, has been found to dramatically lower levels of tau protein in mice with Alzheimer's disease. The vitamin also increased proteins that strengthen microtubules, the scaffolding within brain cells along which information travels. Not only did the vitamin prevent memory loss in Alzheimer’s mice, it also slightly improved cognitive performance in normal mice. Nicotinamide is a water-soluble vitamin sold in health food stores. It generally is safe but can be toxic in very high doses. Clinical trials have shown it benefits people with diabetes complications and has anti-inflammatory properties that may help people with skin conditions. Clinical trials with Alzheimer’s patients are now underway.

Green, K.N. et al. 2008. Nicotinamide Restores Cognition in Alzheimer's Disease Transgenic Mice via a Mechanism Involving Sirtuin Inhibition and Selective Reduction of Thr231-Phosphotau. Journal of Neuroscience, 28, 11500-11510.

http://www.eurekalert.org/pub_releases/2008-11/uoc--vbr103008.php

Vitamin E may help Alzheimer's patients live longer

A study of 847 Alzheimer's patients has found that those who took 1,000 international units of vitamin E twice a day, were 26% less likely to die over a five-year period than people who didn't take vitamin E.  It also appears that taking vitamin E plus a cholinesterase inhibitor may be more beneficial than taking either agent alone.

The research was presented at the American Academy of Neurology Annual Meeting in Chicago, April 12 – April 19.

http://www.eurekalert.org/pub_releases/2008-04/aaon-vem040208.php

Omega-3 fatty acids may slow cognitive decline in some patients with very mild Alzheimer's disease

Several studies have shown that eating fish, which is high in omega-3 fatty acids, may protect against Alzheimer's disease. A Swedish study has now tested whether supplements could have similar effects. Patients with mild-to-moderate Alzheimer’s who took 1.7 grams of DHA and .6g of EPA showed the same rate of cognitive decline as those taking a placebo, however, among a subgroup of 32 patients with very mild cognitive impairment, those who took the fatty acids experienced less decline in six months compared with those who took placebo. It may be that anti-inflammatory effects are an important reason for the benefit, potentially explaining why effects were seen only in those with very early-stage disease, when levels of inflammation seem to be higher.

Freund-Levi;, Y. et al. 2006. w-3 Fatty Acid Treatment in 174 Patients With Mild to Moderate Alzheimer Disease: OmegAD Study: A Randomized Double-blind Trial. Archives of Neurology, 63, 1402-1408.

http://www.eurekalert.org/pub_releases/2006-10/jaaj-ofa100506.php

Dietary supplements offer new hope for Alzheimer's patients

A "cocktail" of dietary supplements (omega-3 fatty acids, uridine and choline) has been found to dramatically increase the amount of membranes that form brain cell synapses in gerbils. The treatment is now in human clinical trials. It is hoped that such treatment may significantly delay Alzheimer's disease. The treatment offers a different approach from the traditional tactic of targeting amyloid plaques and tangles. Choline can be found in meats, nuts and eggs, and omega-3 fatty acids are found in a variety of sources, including fish, eggs, flaxseed and meat from grass-fed animals. Uridine, which is found in RNA and produced by the liver and kidney, is not obtained from the diet, although it is found in human breast milk.

Wurtman, R.J., Ulus, I.H., Cansev, M., Watkins, C.J., Wang L. & Marzloff, G. 2006. Synaptic proteins and phospholipids are increased in gerbil brain by administering uridine plus docosahexaenoic acid orally. Brain Research, Available online ahead of print 21 April 2006.

http://www.eurekalert.org/pub_releases/2006-04/miot-mro042706.php

Compound in wine reduces levels of Alzheimer's disease-causing peptides

In cell studies, resveratrol has been found to lower levels of amyloid-beta peptides. Resveratrol is a natural compound occurring in abundance in grapes, berries and peanuts. The highest concentration has been reported in wines prepared from Pinot Noir grapes. The anti-amyloidogenic effect of resveratrol observed in cell cultures does not however necessarily mean that the beneficial effect can result simply from eating grapes or drinking wine. Further research aims to develop more active and more stable compounds.

Marambaud, P., Zhao, H. & Davies, P. 2005. Resveratrol Promotes Clearance of Alzheimer's Disease Amyloid- Peptides. Journal of Biological Chemistry, 280, 37377-37382.

http://www.eurekalert.org/pub_releases/2005-11/asfb-ciw110305.php

Clinical diagnosis of Alzheimer's may be delayed with donepezil

In a study of people with mild cognitive impairment, those who took the drug donepezil were at reduced risk of progressing to a diagnosis of Alzheimer's during the first years of the trial, but by the end of the 3-year study there was no benefit from the drug. Of the 769 participants, 212 developed possible or probable Alzheimer’s within the 3-year study period; the donepezil group's risk of progression to a diagnosis of Alzheimer’s was reduced by 58% one year into the study, and 36% at 2 years, but no risk reduction at the end of three years. Vitamin E was also tested in the study and was found to have no effect at any point in the study.

Petersen, R.C. et al. 2005. Vitamin E and Donepezil for the Treatment of Mild Cognitive Impairment. New England Journal of Medicine, 352 (23), 2379-2388.

http://www.eurekalert.org/pub_releases/2005-04/nioa-cdo041205.php
http://www.eurekalert.org/pub_releases/2005-04/mc-dia041105.php

Pilot study points to healing power of turmeric

A study using genetically engineered mice has found that those mice on a diet rich in curcumin (the yellow pigment in the curry spice turmeric) developed 85% few Alzheimer’s plaques then the control group. Curcumin has antioxidant, anti-inflammatory, and cholesterol lowering properties, and has long been used in India as treatment for a variety of ailments. A human trial involving 33 Alzheimer's patients will soon commence.

Yang, F., Lim, G.P., Begum, A.N., Ubeda, O.J., Simmons, M.R., Ambegaokar, S.S., Chen, P.P., Kayed, R., Glabe, C.G., Frautschy, S.A. & Cole, G.M. 2004. Curcumin inhibits formation of Abeta oligomers and fibrils and binds plaques and reduces amyloid in vivo. Journal of Biological Chemistry, published online ahead of print December 7, 2004
A copy of the full paper can be found on the Journal of Biological Chemistry Web site athttp://tinyurl.com/5bzbs

http://www.eurekalert.org/pub_releases/2004-12/potn-usn122804.php
http://www.sciencentral.com/articles/view.htm3?article_id=218392455

Dietary supplement helps Alzheimer’s

A three-month study of 55 elderly patients with mild or moderate Alzheimer’s found that those given EV-1, a dietary supplement containing, among other things, the putative antioxidant ingredient of red wine, showed no deterioration during the trial. The supplement is designed to interfere with a defective mitochondrial cycle thought to contribute to the metabolic disturbances associated with late onset Alzheimer’s. The Krebs tricarboxylic acid cycle is fuelled by glucose and regulates levels of reactive oxygen species in the body. EV-1 contains glucose, a compound called malate that primes or maintains the Krebs cycle, and resveratrol - the antioxidant component of red wine that is thought to soak up reactive oxygen species. More studies are needed to confirm this result.

The findings were presented in November at the annual meeting of the Society for Neuroscience (SFN) in New Orleans.

tags lifestyle: 

tags problems: 

Estrogen for Alzheimer's

Older news items (pre-2010) brought over from the old website

For women over 65, Combined Hormone Therapy increases risk of dementia

Much to the researchers’ surprise and disappointment, a four-year experiment involving 4,532 women at 39 medical centers, has found that combined hormone therapy (involving both estrogen and progestin) doubles the risk of Alzheimer's disease and other types of dementia in women who began the treatment at age 65 or older, although the risk is still small : for every 10,000 women 65 and older who take hormones, 23 of the predicted 45 cases of dementia a year, will be attributable to the hormones. The study also found that the combined hormone therapy produced no improvement in general cognitive function, and in fact had adverse effects on cognition among some women. This supports an earlier study suggesting that, while estrogen is helpful to cognitive function in postmenopausal women, the benefits can be cancelled out by progestin / progesterone. The study also confirmed previous research showing that the combination therapy increased the risk of stroke - previous research has indicated that risk factors for stroke are also risk factors for cognitive decline.

Shumaker, S.A., Legault, C., Rapp, S.R., Thal, L., Wallace, R.B., Ockene, J.K., Hendrix, S.L., Jones, B.N. III, Assaf, A.R., Jackson, R.D., Kotchen, J.M., Wassertheil-Smoller, S. & Wactawski-Wende, J. 2003. Estrogen Plus Progestin and the Incidence of Dementia and Mild Cognitive Impairment in Postmenopausal Women: The Women's Health Initiative Memory Study: A Randomized Controlled Trial. JAMA, 289, 2651-2662.

Rapp, S.R., Espeland, M.A., Shumaker, S.A., Henderson, V.W., Brunner, R.L., Manson, J.E., Gass, M.L.S., Stefanick, M.L., Lane, D.S., Hays, J., Johnson, K.C., Coker, L.H., Dailey, M. & Bowen, D. 2003. Effect of Estrogen Plus Progestin on Global Cognitive Function in Postmenopausal Women: The Women's Health Initiative Memory Study: A Randomized Controlled Trial. JAMA, 289, 2663-2672.

Wassertheil-Smoller, S., Hendrix, S., Limacher, M., Heiss, G., Kooperberg, C., Baird, A., Kotchen, T., Curb, J.D., Black, H., Rossouw, J.E., Aragaki, A., Safford, M., Stein, E., Laowattana, S. & Mysiw, W.J. 2003. Effect of Estrogen Plus Progestin on Stroke in Postmenopausal Women: The Women's Health Initiative: A Randomized Trial. JAMA, 289, 2673-2684.

http://www.eurekalert.org/pub_releases/2003-05/wfub-chr052203.php

Animal studies suggest why estrogen can't help after dementia has developed

Research with rats suggests that nerve cells in the brain called cholinergic neurons are needed for estrogen to help learning and memory. This suggests why starting estrogen after dementia has developed is ineffective.

Gibbs, R.B. 2002. Basal Forebrain Cholinergic Neurons Are Necessary for Estrogen to Enhance Acquisition of a Delayed Matching-to-Position T-Maze Task, Hormones and Behavior, 42(3), 245-257.

http://www.eurekalert.org/pub_releases/2002-11/uopm-asp110502.php

Long-term ERT in postmenopausal women with Alzheimer's may worsen memory

A study using female rats investigated the interaction of two conditions known to exist within the brains of female Alzheimer's patients: 1) the presence of chronic neuroinflammation, and 2) having too much or not enough estrogen. They found that rats who had their ovaries removed (to model the condition of post-menopausal women) performed more poorly on a water maze task when they had chronic brain inflammation OR long-term estrogen replacement therapy. Most significantly, those who had both conditions performed much more poorly – beyond what would be expected by either condition alone. That such results extend to postmenopausal women is supported by a 2000 study involving a long term, placebo-controlled study that examined the effects of estrogen replacement therapy on cognitive function in women with mild to moderate Alzheimer's. The effects of ERT were initially beneficial, but the performance of women receiving sustained ERT declined more than that of women receiving the placebo treatment. The results of these studies suggest that postmenopausal women with Alzheimer's disease who undergo long-term estrogen replacement therapy may make their memory loss worse.

Marriott, L.K., Hauss-Wegrzyniak, B., Benton, R.S., Vraniak, P.D. & Wenk, G.L. 2002. Long-Term Estrogen Therapy Worsens the Behavioral and Neuropathological Consequences of Chronic Brain Inflammation. Behavioral Neuroscience, 116 (5), 902-11.

http://www.eurekalert.org/pub_releases/2002-10/apa-lei102202.php

Estrogen patch may improve memory for women with Alzheimer's

A new study suggests that an estrogen skin patch given to women with mild to moderate Alzheimer's disease can improve their memory and attention skills. The study involved only 20 women for eight weeks, and the results will need to be confirmed by a larger-scale study. Research to date has been equivocal about the effects of estrogen on women with Alzheimer's, with some finding a memory-enhancing effect, and others finding no effect. It is speculated that the type of estrogen might be critical. The present study used estradiol, a type of estrogen that has been shown to have an effect on the brain.

Asthana, S., Baker, L. D., Craft, S., Stanczyk, F. Z., Veith, R. C., Raskind, M. A., & Plymate, S. R. (2001). High-dose estradiol improves cognition for women with AD Results of a randomized study. Neurology, 57(4), 605–612. doi:10.1212/WNL.57.4.605

http://www.eurekalert.org/pub_releases/2001-08/aaon-epm082001.php

tags problems: 

Anti-hypertensive drugs

Older news items (pre-2010) brought over from the old website

Some blood pressure drugs may help protect against dementia

High blood pressure is a major contributor to the development of all types of dementia. Data from over 1000 participants in the Cardiovascular Health Study, who were free of dementia when they entered the study and who were being treated for hypertension, has revealed that those taking centrally-active ACE inhibitors (which cross the blood-brain barrier) showed significantly lower rates of mental decline. However, non-centrally active ACE inhibitors were associated with an increased risk of dementia compared to those taking other anti-hypertensive drugs. Centrally-acting ACE inhibitors include captropril (Capoten®), fosinopril (Monopril®), lisinopril (Prinivil® or Zestri®), perindopril (Aceon®), ramipril (Altace®) and trandolapril (Mavik®).

Sink, K.M. et al. 2009. Angiotensin-Converting Enzyme Inhibitors and Cognitive Decline in Older Adults With Hypertension: Results From the Cardiovascular Health Study. Archives of Internal Medicine,169 (13), 1195-1202.

http://www.eurekalert.org/pub_releases/2009-07/wfub-sbp072009.php

Blood pressure drugs may cut risk of Alzheimer's by 40%

Analysis of more than 5 million UK medical records has revealed that those taking drugs known as angiotensin receptor blockers (ARBs), used to treat high blood pressure, had a 35-40% lower risk of developing Alzheimer's disease and similar neurodegenerative disorders. The drugs also appeared to slow the progression of Alzheimer's disease, reducing deaths, admissions to nursing homes and certain symptoms of the condition by up to 45%. The drugs were of most benefit to patients who had experienced a stroke. The most common ARBs are marketed as candesartan, losartan and irbesartan. In the next few months, the study will be repeated using US medical records of a further 3 million patients. It’s reported that the analysis has also identified other drugs that appear to prevent Alzheimer's and some that make the condition worse. A combination of ARBs with other drugs may reduce the risk of dementia by more than 50%.

The findings were presented at the international conference on Alzheimer's disease in Chicago.

http://www.guardian.co.uk/science/2008/jul/28/medicalresearch.health

Anti-hypertensive drug may help prevent and treat Alzheimer's disease

A review of more than 1,500 drugs commercially available for treatment of other disorders, to determine their potential value in treating Alzheimer's disease, identified 7 out of 55 candidate drugs commonly prescribed for the treatment of hypertension as capable of significantly preventing beta-amyloid production. Only one of these drugs — Valsartan — was shown to have a marked in vitro effect, and this drug has now been shown to reduce the severity of Alzheimer’s in genetically engineered mice.

Wang, J. et al. 2007. Valsartan lowers brain ß-amyloid protein levels and improves spatial learning in a mouse model of Alzheimer disease. Journal of Clinical Investigation, 117, 3393-3402.
Full text available at: http://www.jci.org/cgi/reprint/117/11/3393

http://www.eurekalert.org/pub_releases/2007-10/tmsh-adm102307.php
http://www.eurekalert.org/pub_releases/2007-10/joci-dtl101807.php

Some hypertension drugs may help reduce dementia risk

Data from the Cardiovascular Health Study, a long-term study of cardiovascular risk factors that involved 5,888 people over 65 years old, has studied 1,074 participants who were free of dementia when they entered the study and who were being treated for high blood pressure. They found use of a class of high blood pressure medicines that are centrally active ACE inhibitors was associated with lower risk of cognitive decline. The benefit did not result from ACE inhibitors in general, only to those that are centrally active (which means they can cross the blood brain barrier). Centrally acting drugs include captropril (Capoten®), fosinopril (Monopril®), lisinopril (Prinivil® or Zestri®), perindopril (Aceon®), ramipril (Altace®) and trandolapril (Mavik®).

Wolozin B, Lee A, Lee A, Whitmer R, Kazis L. Use of angiotensin receptor blockers is associated with a lower incidence and progression of Alzheimer disease. Presented at: International Conference on Alzheimer’s Disease. CA, USA, 26–31 July 2008 (Abstract O1-05-05).

http://www.eurekalert.org/pub_releases/2007-05/wfub-shd042707.php

Hypertension drugs might help Alzheimer’s

A project to determine whether drugs that are already commercially available for treatment of other disorders might help in treating Alzheimer’s disease using in vitro methods has identified several hundred drugs as having promise in preventing beta-amyloid build-up, of which seven are commonly prescribed to treat hypertension. One drug in particular was identified as effective in blocking the accumulation of beta-amyloid in the brain and preventing the deterioration of cognitive performance: Propranololo-HCL (Inderal), a drug widely prescribed to treat high blood pressure in elderly patients. Of course, clinical trials will need to occur before this can be confirmed.

The research was reported at the American College of Neuropsychopharmacology’s (ACNP) annual conference December 3 - 7, 2006, in Hollywood, FL.

http://www.eurekalert.org/pub_releases/2006-12/g-nsf120106.php

tags problems: 

Anti-inflammatory drugs

Older news items (pre-2010) brought over from the old website

Pain relievers don’t prevent Alzheimer's in the very elderly

In contrast to a number of studies indicating benefits of nonsteroidal anti-inflammatory drugs (NSAIDs) in preventing Alzheimer’s, a large, long-running study following 2,736 members of a healthcare delivery system for 12 years, has revealed that not only did use of these drugs not reduce the risk of developing dementia, the risk among these very elderly (most were over age 83 when they developed dementia) was 66% higher among heavy NSAID users than among people who used little or no NSAIDs. Heavy use was defined as having prescriptions for NSAIDs at least 68% of the time in two years. Although this seems to contradict earlier research, it may be consistent with the theory that NSAID use delays the onset of Alzheimer's – thus, studies of younger NSAID users would show fewer Alzheimer's cases, while groups of older people might show more cases.

Breitner, J.C.S. et al. 2009. Risk of dementia and AD with prior exposure to NSAIDs in an elderly community-based cohort. Neurology, Published online April 22, 2009.

http://www.eurekalert.org/pub_releases/2009-04/ghcc-prs041709.php

Inflammatory response to infection and injury may worsen dementia

Systemic inflammation – inflammation in the body as a whole – is known to have direct effects on brain function, but there has been little research into the impact of systemic inflammation on the progress of dementia and neurodegenerative diseases. Now, in a study to mimic the effect of bacterial infection in people with dementia, a mouse study has revealed that that the inflammatory response to infection in mice with prior neurodegenerative disease leads to exaggerated symptoms of the infection, causes changes in memory and learning and leads to accelerated progression of dementia.

Cunningham, C. et al. In press. Systemic Inflammation Induces Acute Behavioral and Cognitive Changes and Accelerates Neurodegenerative Disease. Biological Psychiatry.

http://www.eurekalert.org/pub_releases/2008-09/wt-irt091608.php

Anti-inflammatory drugs do not improve cognitive function in older adults

Previous studies have suggested that nonsteroidal anti-inflammatory drugs are associated with a lower risk of developing Alzheimer’s. A clinical trial involving over 2000 older adults (70+) with a family history of Alzheimer’s disease compared a twice daily treatment of 200 milligrams of either the NSAID celecoxib, or the NSAID naproxen sodium, or a placebo. The trial lasted from March 2001 to December 2004. The study found not only that NSAIDs didn’t improve cognitive function, but that naproxen (but not celecoxib) was associated with significantly lower cognitive performance.

ADAPT Research Group. 2008. Cognitive Function Over Time in the Alzheimer's Disease Anti-inflammatory Prevention Trial (ADAPT): Results of a Randomized, Controlled Trial of Naproxen and Celecoxib. Archives of Neurology, 65(7), (doi:10.1001/archneur.2008.65.7.nct70006).

http://www.eurekalert.org/pub_releases/2008-05/jaaj-add050808.php

Ibuprofen linked to reduced risk of Alzheimer's disease

A very large five-year study of older veterans (55+) has found that those who  used ibuprofen for more than five years were more than 40% less likely to develop Alzheimer’s disease. Results also showed that the longer ibuprofen was used, the lower the risk for dementia. Other types of NSAIDs, such as indomethacin, were associated with a 25% reduced risk, however others, such as celecoxib, didn’t show any benefit. There was no obvious connection between those which were associated with reduced risk and those that weren’t. It may be that the effect is a product of some other cause.

Vlad, S.C. et al. 2008. Protective effects of NSAIDs on the development of Alzheimer disease. Neurology, 70, 1672-1677.

http://www.eurekalert.org/pub_releases/2008-05/aaon-ilt042908.php

Ibuprofen, aspirin, naproxen may be equally effective at reducing Alzheimer's risk

And demonstrating that the jury is still out on NSAIDs, a review of six studies has found that people who used NSAIDs had a 23% lower risk of developing Alzheimer’s disease compared to those who never used NSAIDs. The risk reduction did not appear to depend upon the type of NSAID taken. However, the researchers were specifically looking for a difference between those NSAIDs that lower Aβ1-42 amyloid, which was what they didn’t find — and this agrees with the finding of the large veteran study. The findings of this study then may be taken as supporting the view that specific NSAIDs may be of benefit rather than a particular class of them.

Szekely, C.A. et al. 2008. No advantage of Aβ42-lowering NSAIDs for prevention of Alzheimer dementia in six pooled cohort studies. Neurology, 70, 2291-2298.

http://www.eurekalert.org/pub_releases/2008-05/aaon-ian052008.php

Low dose aspirin does not protect women against cognitive decline

Evidence that aspirin and other anti-inflammatory drugs may protect against dementia has been inconclusive. Now a large, long-running study involving 6,377 women aged 65 years or more, over ten years, has found that those who took low dose aspirin (100 mg on alternate days) performed at similar levels to a placebo group on cognitive tests. However, there was evidence of benefit in one very specific area of cognition: category fluency.

[850] Kang, J H., Cook N., Manson JA., Buring J. E., & Grodstein F.
(2007).  Low dose aspirin and cognitive function in the women's health study cognitive cohort.
BMJ. 334(7601), 987 - 987.

Full text is available at http://tinyurl.com/25kzxf

http://www.eurekalert.org/pub_releases/2007-04/bmj-lda042607.php

Conflicting results about benefit of anti-inflammatory drugs

It’s long been known that patients regularly taking nonsteroidal anti-inflammatory drugs, such as ibuprofen and naproxen, seem to have less risk of developing Alzheimer's. It’s been suggested that this might mean that Alzheimer's is a product of inflammation in the brain, and that damage happens when the microglia, the brain's immune cells, become overactive and attack healthy neurons. A new study of autopsy brain tissue, and of in vitro rat cultures indicates that, on the contrary, what’s happening is that, as microglia age, they lose their ability to protect the brain. Moreover, the latest study into the effects of anti-inflammatory drugs found no benefit for those suffering from Alzheimer’s. Indeed, it is possible that such drugs might exacerbate the problem. It is speculated that microglia may have the potential to both protect and attack neurons. The key may lie in the way microglia interact with beta-amyloid protein.

http://www.scientificamerican.com/article.cfm?id=brain-not-inflamed

Anti-inflammatories lower Alzheimer disease–related protein levels in mice

Following earlier research showing three commonly used nonsteroidal anti-inflammatory drugs (NSAIDs) were capable of selectively lowering the levels of Abeta42 (an isoform of the amyloid beta protein) in mice, investigation of 20 commonly used NSAIDs found 8 FDA-approved drugs successfully lowered Abeta42 levels in mice at doses achievable in humans.

Eriksen, J.L. et al. 2003. NSAIDs and enantiomers of flurbiprofen target γ-secretase and lower Aß42 in vivo. Journal of Clinical Investigation, 112, 440-449.

http://www.eurekalert.org/pub_releases/2003-08/joci-fds072503.php

Anti-inflammatories offer some protection against developing Alzheimer's

A review of 9 observational studies that examined the role of NSAID use in preventing Alzheimer's disease found the pooled relative risk of Alzheimer's disease among users of NSAIDs was 0.72. The risk was 0.95 among short term users (< 1 month), 0.83 among intermediate term (mostly < 24 months) and 0.27 for long term (mostly > 24 months) users. The pooled relative risk in 8 studies of aspirin use was 0.87. It was concluded that NSAIDs offer some protection against the development of Alzheimer's disease.

Etminan, M., Gill, S. & Samii, A. 2003. Effect of non-steroidal anti-inflammatory drugs on risk of Alzheimer's disease: systematic review and meta-analysis of observational studies. BMJ, 327, 128.

Buildup of amyloid plaques linked to gene inhibition

Examination of genetically engineered mice and of brain tissue from deceased Alzheimer's patients has found that the buildup of amyloid plaques in the brain dramatically inhibits six genes known to be important for the formation of new memories. The finding suggests a new approach to the treatment of Alzheimer’s disease, combining amyloid-lowering treatment with other strategies designed to block the effect of amyloid on these genes.

Dickey, C.A. et al. 2003. Selectively Reduced Expression of Synaptic Plasticity-Related Genes in Amyloid Precursor Protein + Presenilin-1 Transgenic Mice. Journal of Neuroscience, 23, 5219-5226.

http://www.eurekalert.org/pub_releases/2003-06/uosf-sla062503.php

tags problems: 

Exelon

Older news items (pre-2010) brought over from the old website

Drugs used to treat Alzheimer's in nursing homes are worsening sufferers' illness

A study of 93 patients with dementia has found that quetiapine, an anti-psychotic drug commonly used in nursing homes to treat agitation and related symptoms in people with Alzheimers' disease, actually worsens patients' illness, significantly speeding up their rate of cognitive decline. Unfortunately, quetiapine had been regarded as one of the safer of the antipsychotic drugs available. There have been safety concerns with the two most commonly used antipsychotic drugs in people with dementia, risperidone and olanzapine, because of increased risk of stroke. Participants in the trial who were taking rivastigmine showed little or no worsening of their illness. Neither drug had any effect on agitation.

Ballard, C. et al. 2005. Quetiapine and rivastigmine and cognitive decline in Alzheimer's disease: Randomised double blind placebo controlled trial. British Medical Journal, 330, 874-7.

http://www.eurekalert.org/pub_releases/2005-02/bmj-dut021605.php

Exelon more effective than thought

Exelon ® (rivastigmine tartrate) is one of the drugs used to treat the symptoms of mild-to-moderate Alzheimer’s. A new study suggests that the effects of Exelon might be more significant than was thought — it may be able to delay progression of the disease. The study found that 26 weeks after discontinuing treatment , those who had been on Exelon showed less cognitive decline than patients who had previously taken a placebo.

Farlow, M., Potkin, S., Koumaras, B., Veach, J. & Mirski, D. 2003. Analysis of Outcome in Retrieved Dropout Patients in a Rivastigmine vs Placebo, 26-Week, Alzheimer Disease Trial. Archives of Neurology, 60, 843-848.

http://www.eurekalert.org/pub_releases/2003-06/iu-mms061703.php

Exelon found to reduce cognitive decline in mild to moderate Alzheimer's patients

A one-year study found rivastigmine tartrate (Exelon®) reduces the cognitive decline of people with mild to moderate Alzheimer's disease. 545 patients completed the initial six-month phase of the trial and 532 then agreed to extend the trial another six months. Patients who received the higher dose of rivastigmine from the beginning had higher cognitive scores at the end than those patients who received a placebo or the lower dose during the first six months. This suggests early treatment with a high dose may provide benefits that are lost if treatment is delayed.

Farlow, M., Anand, R., Messina Jr, J., Hartman, R., & Veach, J. (2000). A 52-Week Study of the Efficacy of Rivastigmine in Patients with Mild to Moderately Severe Alzheimer’s Disease. European Neurology, 44(4), 236–241. doi:10.1159/000008243

http://www.eurekalert.org/pub_releases/2000-11/IU-Rtrc-0811100.php

tags problems: 

Aricept

Older news items (pre-2010) brought over from the old website

Risk of abnormally slow heart rate twice as high in those taking Alzheimer's drugs

Data from 1.4 million Canadians aged 67 and older has revealed that older patients hospitalized with bradycardia were more than twice as likely to have recently started on a cholinesterase inhibitor such as donepezil for Alzheimer's disease compared to those without bradycardia. Bradycardia is an abnormally slow resting heart rate (under 60 beats per minute). Although it can be asymptomatic, it can also cause fainting, palpitations, shortness of breath, or even death. Although there are three cholinesterase-inhibiting drugs approved for use in Canada, most had been prescribed donepezil. The findings add weight to recent guidelines suggesting that doctors should not prescribe cholinesterase inhibitors for dementia patients as a matter of course, but weigh the potential risks and benefits.

Park-Wyllie, L. Y., Mamdani, M. M., Li, P., Gill, S. S., Laupacis, A., & Juurlink, D. N. (2009). Cholinesterase Inhibitors and Hospitalization for Bradycardia: A Population-Based Study. PLoS Med, 6(9), e1000157. doi: 10.1371/journal.pmed.1000157. Full text available at http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.1000157

http://www.eurekalert.org/pub_releases/2009-10/smh-roa100109.php

Depression may increase risk of Alzheimer's disease in people with memory problems

A three-year study involving 756 people with mild cognitive impairment found increases in depressive symptoms was positively associated with increased risk in developing Alzheimer’s. The study also found that, for those who were depressed, taking the Alzheimer’s drug donepezil significantly reduced the risk of developing Alzheimer’s, compared to those taking vitamin E or placebo. Donepezil had little effect on those who were not depressed.

Lu, P.H. et al. 2009. Donepezil delays progression to AD in MCI subjects with depressive symptoms. Neurology, 72, 2115-2121.

http://www.eurekalert.org/pub_releases/2009-06/aaon-dmi060909.php

Support for Alzheimer's drug Aricept

A small sample of adults with mild age-related memory loss was randomly assigned a daily placebo or Aricept. Although both groups scored the same on memory tests, PET brain scans before and after 18 months of treatment showed that those given Aricept had an increased rate of metabolism and looked more normal than the brains of those who took the placebo. It’s suggested that the treatment of early symptoms of memory loss may protect the brain.

The findings were presented July 30 at the International Conference on Alzheimer's Disease 2008.

http://www.eurekalert.org/pub_releases/2008-07/uoc--uis072808.php

Drug improves symptoms of severe Alzheimer's disease

A six-month study involving 343 people with severe Alzheimer’s disease has found that donepezil, a drug used to treat mild to moderate Alzheimer’s, stabilized or improved cognitive function in 63% of those taking donepezil compared to 39% of those taking placebo. Compared to the placebo group, those taking donepezil showed improvement in memory, language, attention, and recognizing one’s name. The donepezil group also showed less of a decline in social interaction, skills needed to complete a jigsaw puzzle, and arranging sentences compared to the placebo group.

Black, S.E. et al. 2007. Donepezil preserves cognition and global function in patients with severe Alzheimer disease. Neurology, 69, 459-469.

http://www.eurekalert.org/pub_releases/2007-07/aaon-dis072407.php

Donezepil slows brain deterioration for some on road to Alzheimer's

According to a new study, the drug donepezil measurably (but still only slightly) slows the rate of hippocampal shrinkage in patients with mild cognitive impairment (a pre-Alzheimer's condition) who carried the apolipoprotein E4 (APOE 4) gene variant. The study involved 131 patients with mild cognitive impairment. For APOE 4 carriers, the rate of hippocampal atrophy was 4.5% per year, versus 6.14% in placebo-treated patients. Rates of shrinkage for cognitively normal people in their late 70s are approximately 1.4 percent per year. Vitamin E had no significant effect on atrophy for any patients.

Findings were presented July 17 at the Alzheimer's Association International Conference on Alzheimer's Disease and Related Disorders in Madrid, Spain.

http://www.eurekalert.org/pub_releases/2006-07/mc-msd071306.php

New memory drug works best in combination with older drug

An experimental drug – a compound known as SGS742 – has been successful in animal studies in improving memory, and is now in human clinical trials. The drug works by blocking certain chemicals that interfere with memory formation, thus enabling better acquisition and retention of new information. It alters the activity of gene control machinery that is important for memory consolidation. It was most effective when used in conjunction with Aricept, an established Alzheimer’s drug.

Helm, K.A., Haberman, R.P., Dean, S.L., Hoyt, E.C., Melcher, T., Lund, P.K. & Gallagher, M. 2005. GABAB receptor antagonist SGS742 improves spatial memory and reduces protein binding to the cAMP response element (CRE) in the hippocampus. Neuropharmacology, 48(7), 956-64

http://www.eurekalert.org/pub_releases/2005-06/jhu-nmd060905.php

Clinical diagnosis of Alzheimer's may be delayed with donepezil

In a study of people with mild cognitive impairment, those who took the drug donepezil were at reduced risk of progressing to a diagnosis of Alzheimer's during the first years of the trial, but by the end of the 3-year study there was no benefit from the drug. Of the 769 participants, 212 developed possible or probable Alzheimer’s within the 3-year study period; the donepezil group's risk of progression to a diagnosis of Alzheimer’s was reduced by 58% one year into the study, and 36% at 2 years, but no risk reduction at the end of three years. Vitamin E was also tested in the study and was found to have no effect at any point in the study.

Petersen, R.C. et al. 2005. Vitamin E and Donepezil for the Treatment of Mild Cognitive Impairment. New England Journal of Medicine, 352 (23), 2379-2388.

http://www.eurekalert.org/pub_releases/2005-04/nioa-cdo041205.php
http://www.eurekalert.org/pub_releases/2005-04/mc-dia041105.php

Donepezil may have short-term benefit for mild cognitive impairment

Preliminary data from a recently completed clinical trial of 769 patients with mild cognitive impairment indicates that those taking the drug donepezil were at reduced risk of progressing to Alzheimer's disease for 18 months. The reduced risk disappeared after 18 months, and by the end of the 3-year study, the probability of progressing to Alzheimer’s was the same in the two groups. The study compared donepezil, vitamin E, or placebo. There was no apparent benefit from vitamin E.

The data were presented at the Alzheimer Association's 9th International Conference on Research on AD and Related Disorders (ICAD) in Philadelphia on July 18, 2004.

http://www.eurekalert.org/pub_releases/2004-07/nioa-dmh071504.php
http://www.eurekalert.org/pub_releases/2004-07/mc-tcs071504.php

Doubt over effectiveness of cholinesterase inhibitors for treatment of Alzheimer's

A study involving 565 Alzheimer’s patients has found that while donepezil did improve tests of mental and functional ability over the first 2 years of treatment, the improvement was slight, and there was no significant delay in institutionalization or progression of disability. There were also no differences between donepezil and placebo in behavioral and psychological symptoms, formal care costs, unpaid caregiver time, adverse events or deaths, or between the two doses of donepezil used in the study.

AD2000 Collaborative Group. 2004. Long-term donepezil treatment in 565 patients with Alzheimer's disease (AD2000): randomised double-blind trial. The Lancet, 363 (9427), 2105-15.

http://www.eurekalert.org/pub_releases/2004-06/l-doe062304.php

ARICEPT® helpful in treating patients with severe Alzheimer's

A new analysis from the Moderate to Severe Alzheimer's Disease Study (MSAD), previously published in Neurology in August 2001, suggests that ARICEPT® may also be helpful to those with more advanced Alzheimer’s. The study involved 145 patients with severe Alzheimer's disease who were residing in the community or in assisted living settings. Patients requiring total nursing care were ineligible. ARICEPT®-treated patients showed cognitive improvement ; improved or stable global function; less decline on activities of daily living; fewer behavioral disturbances. Some 10% had to drop out because of adverse reactions.

The data were presented at the American Academy of Neurology (AAN) 55th Annual Meeting.

http://www.eurekalert.org/pub_releases/2003-04/ei-nsf040303.php

ARICEPT better than Reminyl for cognition

Results from the first study to directly compare the two Alzheimer drugs, ARICEPT® (donepezil HCl tablets) and Reminyl® (galantamine HBr tablets), found that ARICEPT-treated patients showed significant benefit over patients receiving Reminyl®. Not only were cognitive benefits greater, but ARICEPT® was tolerated significantly better.

The study was presented at the 7th International Geneva/Springfield Symposium on Advances in Alzheimer Therapy (AAT) in Geneva, Switzerland.

http://www.eurekalert.org/pub_releases/2002-04/pn-asi040302.php

Aricept helpful for those with moderate to severe Alzheimer's

The benefits of ARICEPT® (donepezil hydrochloride) may extend into more advanced stages of Alzheimer's disease than previously investigated, according to a first-ever published study of ARICEPT® in patients with moderate to severe Alzheimer's disease, which found significant benefits in patient function, cognition, behavior, and activities of daily living, with very good tolerability. ARICEPT® is approved for the treatment of symptoms of mild to moderate Alzheimer’s disease. Further study of ARICEPT® in patients with severe Alzheimer's disease is currently under way.

Feldman, H., Gauthier, S., Hecker, J., Vellas, B., Subbiah, P., & Whalen, E. (2001). A 24-week, randomized, double-blind study of donepezil in moderate to severe Alzheimer’s disease. Neurology, 57(4), 613–620. doi:10.1212/WNL.57.4.613

http://www.eurekalert.org/pub_releases/2001-08/pn-fps082701.php

Alzheimer's patients taking Aricept maintain daily activities longer

In a 54-week U.S. study of 415 people with mild to moderate Alzheimer's, patients who took the drug donepezil maintained their level of functioning in everyday activities such as shopping and fixing meals, 72 percent longer than those who received a placebo did. The study measured the amount of time before patients' functioning declined based on a clinical rating scale. Those taking donepezil declined, on average, five months later than the people taking the placebo.
Another study found that patients with mild to moderate Alzheimer's disease taking placebo declined by about twice as much as those taking donepezil, based on a scale of cognitive ability, functioning in daily activities and other factors. The one-year study involved 286 people in Scandinavia and the Netherlands.

Mohs, R. C., Doody, R. S., Morris, J. C., Ieni, J. R., Rogers, S. L., Perdomo, C. A., & Pratt, R. D. (2001). A 1-year, placebo-controlled preservation of function survival study of donepezil in AD patients. Neurology, 57(3), 481–488. doi:10.1212/WNL.57.3.481

Winblad, B., Engedal, K., Soininen, H., Verhey, F., Waldemar, G., Wimo, A., … Subbiah, P. (2001). A 1-year, randomized, placebo-controlled study of donepezil in patients with mild to moderate AD. Neurology, 57(3), 489–495. doi:10.1212/WNL.57.3.489

http://www.eurekalert.org/pub_releases/2001-08/aaon-apt080601.php

The drug Aricept might be more effective for Alzheimers sufferers than previously thought

A new study has demonstrated that the drug Aricept® can "switch on" brain cells thought to be irreparably damaged in Alzheimers sufferers. Previous research suggested Aricept had no such dramatic effects. The new findings may enable more effective use to be made of the drug.

www.guardian.co.uk/Archive/Article/0,4273,4080005,00.html

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Reminyl

Older news items (pre-2010) brought over from the old website

Reduced risk of institutionalization in patients with dementia

A study of 596 patients from 7 countries found that dementia patients receiving long-term treatment with REMINYL (more than 36 months) may be able to stay at home for longer compared to those receiving treatment for shorter periods of time. Experts believe the long-term clinical efficacy of galantamine may be because as well as enhancing levels of the neurotransmitter acetylcholine, it also (unlike other treatments), has a modulating effect on the brain's nicotinic receptors, which is believed to increase their effectiveness. Nicotinic receptors are thought to play a key role in attention, memory and learning.

Pirttilä, T., van Baelen, B. & Kavanagh, S. 2004. Effect of galantamine on time to residential or nursing home admission. Poster presented at the 17th European Congress of Neuropsychopharmacology, Stockholm, Sweden 2004.

http://www.eurekalert.org/pub_releases/2004-11/rc-rro110904.php

Patients' medications eases caregiver distress

In a new analysis of an earlier study, researchers have discovered that the drugs currently used to alleviate the symptoms of Alzheimer’s not only help confusion and memory loss, but also alleviates or delays symptoms like agitation, depression, and psychosis, and thus have flow-on effects of alleviating the burden on caregivers. For patients not already exhibiting behavioral problems, treatment with galantamine delayed their symptoms for more than three years on average. This is added impetus to treat patients with dementia with cholinesterase inhibitors as early as possible.

Cummings, J.L., Schneider, L., Tariot, P.N., Kershaw, P.R. & Yuan, W. 2004. Reduction of Behavioral Disturbances and Caregiver Distress by Galantamine in Patients With Alzheimer’s Disease. American Journal of Psychiatry, 161, 532-538.

http://www.eurekalert.org/pub_releases/2004-04/uorm-crt040504.php

ARICEPT better than Reminyl for cognition

Results from the first study to directly compare the two Alzheimer drugs, ARICEPT® (donepezil HCl tablets) and Reminyl® (galantamine HBr tablets), found that ARICEPT-treated patients showed significant benefit over patients receiving Reminyl®. Not only were cognitive benefits greater, but ARICEPT® was tolerated significantly better.

The study was presented at the 7th International Geneva/Springfield Symposium on Advances in Alzheimer Therapy (AAT) in Geneva, Switzerland.

http://www.eurekalert.org/pub_releases/2002-04/pn-asi040302.php

Reminyl may help those with vascular dementia

Reminyl (galantamine) may be effective in treating dementia in patients with cerebrovascular disease, such as stroke. Data from a study presented at the XVII World Congress of Neurology show that Reminyl improves memory, orientation and language skills of patients with vascular dementia or a combination of Alzheimer's disease and cerebrovascular disease ("mixed" dementia) for at least 12 months. The results also showed that Reminyl improved or maintained the ability of these individuals to perform normal activities of daily living, such as bathing, dressing and doing housework. However, Reminyl is not yet approved for the treatment of vascular dementia.

http://www.eurekalert.org/pub_releases/2001-06/K-DsnA-1806101.php

Potential impact of Reminyl on caregiver 'burden' in Alzheimer's disease

Several studies presented at the Tenth Congress of the International Psychogeriatric Association (IPA) assessed the impact of Reminyl treatment on patient functioning by exploring the resulting impact on time required of family caregivers. One study of 435 patients from Europe and Canada, focused on the time caregivers spent supervising their family members or assisting them with activities of daily living, such as dressing and bathing. It was found that the time required to supervise patients who received a placebo increased by approximately two hours per day over the six months, while the time spent supervising individuals who took Reminyl did not increase significantly. In addition, the time that caregivers spent assisting patients on placebo with daily-living activities increased steadily throughout the trial, totalling an average of 23 extra minutes per day by the end of six months. On the other hand, caregivers of patients taking Reminyl reported a decrease in the amount of time spent assisting their charges by an average of 38 minutes per day.
A different study focused on caregiver distress and analysed data from a five-month study of 286 U.S. patients. Participating caregivers rated the degree of distress they experienced in response to 10 types of patient symptoms, such as hallucinations, delusions and agitation. The analysis found that after five months, distress significantly increased among those caring for patients who took placebo. In contrast, distress scores were not significantly different at the end of the study than at the beginning for those caring for persons who received Reminyl.

http://www.eurekalert.org/pub_releases/2001-09/k-sod091301.php

Galantamine therapy shows sustained cognitive benefits for Alzheimer's patients

Previous studies have demonstrated the benefits of galantamine (Reminyl™) treatment in terms of efficacy and safety in the short-term. A recent study followed 636 Alzheimer’s patients over two years, and found that patients receiving galantamine throughout the study maintained cognitive benefits, while the placebo comparison group declined. Moreover, the cognitive benefits of galantamine increased over time, relative to the predicted rates of decline in untreated patients.

The study was presented at the American Academy of Neurology's 53rd Annual Meeting in Philadelphia.

http://www.eurekalert.org/pub_releases/2001-05/AAoN-Gtss-0905101.php
http://my.webmd.com/condition_center_content/alz/article/1728.79858

Another drug for Alzheimer's sufferers

Another drug for Alzheimer's sufferers has been approved by the FDA. Reminyl® is of the same nature as the other three medications already available( Cognex®, Aricept®, and Exelon®). These are all cholinesterase inhibitors; they interfere with the action of an enzyme that would otherwise reduce the brain's supply of acetylcholine, a chemical messenger that is essential for thought processes and nerve function.

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Approved Alzheimer's Drugs

Older news items (pre-2010) brought over from the old website

 

Mixed pathology of dementia indicates combination therapies needed

Data from the Medical Research Council's Cognitive Function and Ageing Study, including post-mortem study of the brains of 456 participants, has enabled researchers to estimate the contribution of each type of pathology to dementia in the population as a whole. The main pathological contributors to dementia were age (18%), small brain (12%), amyloid plaques (8%) and neurofibrillary tangles (11%), small blood vessel disease (12%), multiple vascular pathologies (9%), and hippocampal atrophy (10%). Other significant factors include cerebral amyloid angiopathy (7%) and Lewy bodies (3%). The findings support to the need for a range of strategies, and combination therapies, tailored to the particular needs of the patient. It also points to why particular therapies may be more successful with some individuals but not others.

Matthews, F. E., Brayne, C., Lowe, J., McKeith, I., Wharton, S. B., & Ince, P. (2009). Epidemiological Pathology of Dementia: Attributable-Risks at Death in the Medical Research Council Cognitive Function and Ageing Study. PLoS Med, 6(11), e1000180. doi: 10.1371/journal.pmed.1000180. Full text available at http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.1000180

http://www.eurekalert.org/pub_releases/2009-11/plos-utp110409.php

Recommended: Use of antipsychotic drugs for dementia patients should be curtailed

A report just out from the U.K. Department of Health has concluded that as many as 144,000 dementia patients are being given anti-psychotic drugs unnecessarily, and that excessive use of the medication causes an estimated 1,800 deaths and almost as many strokes every year. It recommended that the use of the drugs could be cut by two-thirds over the course of the next three years, but urged carers and family not to act hastily, warning that stopping prescriptions immediately for many patients could be dangerous.

http://www.guardian.co.uk/society/2009/nov/12/anti-psychotic-drugs-kill-dementia-patients
http://news.bbc.co.uk/2/hi/health/8356423.stm

Risk of abnormally slow heart rate twice as high in those taking Alzheimer's drugs

Data from 1.4 million Canadians aged 67 and older has revealed that older patients hospitalized with bradycardia were more than twice as likely to have recently started on a cholinesterase inhibitor such as donepezil for Alzheimer's disease compared to those without bradycardia. Bradycardia is an abnormally slow resting heart rate (under 60 beats per minute). Although it can be asymptomatic, it can also cause fainting, palpitations, shortness of breath, or even death. Although there are three cholinesterase-inhibiting drugs approved for use in Canada, most had been prescribed donepezil. The findings add weight to recent guidelines suggesting that doctors should not prescribe cholinesterase inhibitors for dementia patients as a matter of course, but weigh the potential risks and benefits.

Park-Wyllie, L. Y., Mamdani, M. M., Li, P., Gill, S. S., Laupacis, A., & Juurlink, D. N. (2009). Cholinesterase Inhibitors and Hospitalization for Bradycardia: A Population-Based Study. PLoS Med, 6(9), e1000157. doi: 10.1371/journal.pmed.1000157. Full text available at http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.1000157

http://www.eurekalert.org/pub_releases/2009-10/smh-roa100109.php

Dementia drugs have greater side-effects than thought

A very large study has found that use of cholinesterase inhibitors (the Alzheimer’s drugs Aricept, Exelon and Reminyl) is associated with increased rates of fainting, slowed heartrate, pacemaker insertion, and hip fracture. Both the injuries incurred from falling and the risks from pacemaker implants are "downstream consequences" of not recognizing that fainting and slowed heartrate may be a consequence of taking these drugs.

Gill, S.S. et al. 2009. Syncope and Its Consequences in Patients With Dementia Receiving Cholinesterase Inhibitors: A Population-Based Cohort Study. Archives of Internal Medicine, 169 (9), 867-873.

http://www.eurekalert.org/pub_releases/2009-05/qu-ddm052709.php

Benefit of combination therapy for Alzheimer's

The first long-term study of the real-world use of Alzheimer's drugs has found that extended treatment with Alzheimer's disease drugs can significantly slow the rate at which the disorder advances, and combination therapy with two different classes of drugs (cholinesterase inhibitors and memantine) is even better at helping patients maintain their ability to perform daily activities. The results showed significant differences in the rate of symptom progression among all three groups – with the smallest level of decline in those receiving combination therapy. Cholinesterase inhibitors are approved for use in mild to moderate dementia, while memantine has been approved for advanced dementia. But these findings suggest there may be an advantage in prescribing both types of drugs as initial treatment.

Atri, A. et al. 2008. Long-term Course and Effectiveness of Combination Therapy in Alzheimer Disease. Alzheimer Disease & Associated Disorders, 22(3), 209-221.

http://www.eurekalert.org/pub_releases/2008-09/mgh-scb092208.php

Drugs may not delay onset of dementia

A review of six clinical trials that had addressed the use of cholinesterase inhibitors (donepezil, rivastigmine and galantamine) with MCI patients has found that in none of the trials did the use of the drugs significantly reduce the rate of progression from MCI to dementia.

Raschetti, R., Albanese, E., Vanacore, N. & Maggini, M. 2007. Cholinesterase inhibitors in mild cognitive impairment: A systematic review of randomised trials. PLoS Medicine, 4(11), e338. Full text available at http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0040338

http://www.eurekalert.org/pub_releases/2007-11/plos-dmn112207.php

Negative review of recommended Alzheimer's drugs

A review of the 22 published, double-blind, randomised trials of the three cholinesterase inhibitors currently recommended for Alzheimer’s disease (donepezil, rivastigmine, and galantamine) has found considerable flaws in the methodology of all trials, and concluded that “Because of flawed methods and small clinical benefits, the scientific basis for recommendations of cholinesterase inhibitors for the treatment of Alzheimer's disease is questionable.”

Kaduszkiewicz, H., Zimmermann, T., Beck-Bornholdt, H-P. & van den Bussche, H. 2005. Cholinesterase inhibitors for patients with Alzheimer's disease: systematic review of randomised clinical trials. British Medical Journal, 331, 321-327.

Anti-inflammatory function of Alzheimer's disease drugs revealed

Current Alzheimer’s drugs focus on preventing the breakdown of acetylcholine. Acetylcholine-producing cells are among the first to die in Alzheimer's patients. Research has also shown that the brains of Alzheimer's patients are characterized by excessive immune activation and inflammation, which are induced by overproduction of an inflammation-producing protein called interleukin-1 and related compounds. Now a new study has found that current Alzheimer's drugs cause a marked reduction in the production of interleukin-1. The findings suggest a new interpretation of why acetylcholine is important; when the acetylcholine increases (as a result of the drug), there is a reduction of the production of interleukin-1. The study also describes the use of a new drug (EN101) which produces these effects in a more efficient way than known heretofore by destroying the molecular antecedent (messenger RNA) of the enzyme, rather than simply blocking the enzyme's activity.

Pollak, Y., Gilboa, A., Ben-Menachem, O., Ben-Hur, T., Soreq, H. & Yirmiya, R. 2005. Acetylcholinesterase inhibitors reduce brain and blood interleukin-1 g production. Annals of Neurology, 57(5), 741-745.

http://www.eurekalert.org/pub_releases/2005-07/thuo-afo072805.php

Drugs used to treat Alzheimer's in nursing homes are worsening sufferers' illness

A study of 93 patients with dementia has found that quetiapine, an anti-psychotic drug commonly used in nursing homes to treat agitation and related symptoms in people with Alzheimers' disease, actually worsens patients' illness, significantly speeding up their rate of cognitive decline. Unfortunately, quetiapine had been regarded as one of the safer of the antipsychotic drugs available. There have been safety concerns with the two most commonly used antipsychotic drugs in people with dementia, risperidone and olanzapine, because of increased risk of stroke. Participants in the trial who were taking rivastigmine showed little or no worsening of their illness. Neither drug had any effect on agitation.

Ballard, C. et al. 2005. Quetiapine and rivastigmine and cognitive decline in Alzheimer's disease: Randomised double blind placebo controlled trial. British Medical Journal, 330, 874-7.

http://www.eurekalert.org/pub_releases/2005-02/bmj-dut021605.php

Research clarifies how Alzheimer's medicines work

New research clarifies how cholinesterase inhibitors alleviate mild-to-moderate Alzheimer's. When scientists chemically blocked receptors for an important neurotransmitter called acetylcholine, even healthy young people found it significantly harder to learn and remember – especially in the face of interference. Cholinesterase inhibitors slow the breakdown of acetylcholine. The finding also helps explain why Parkinson's disease, dementia due to multiple strokes, multiple sclerosis and schizophrenia, are all also associated with memory problems — all these conditions, like Alzheimer’s, are associated with lower levels of acetylcholine in the brain.

Atri, A., Norman, K.A., Nicolas, M.M., Cramer, S.C., Hasselmo, M.E., Sherman, S., Kirchhoff, B.A., Greicius, M.D., Breiter, H.C. & Stern, C.E. 2004. Central Cholinergic Receptors Impairs New Learning and Increases Proactive Interference in a Word Paired-Associate Memory Task. Behavioral Neuroscience, 118 (1).

http://www.eurekalert.org/pub_releases/2004-02/apa-rch020904.php

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Physical activity saves hippocampus in people at risk of Alzheimer's

A study involving 97 healthy older adults (65-89) has found that those with the “Alzheimer’s gene” (APOe4) who didn’t engage in much physical activity showed a decrease in hippocampal volume (3%) over 18 months. Those with the gene who did exercise showed no change in the size of their

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