treatment

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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Memantine

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

Benefit of memantine in the treatment of Alzheimer's disease not proven

A review of the use of memantine for patients with moderate or severe Alzheimer's disease has concluded there is no scientific evidence of any benefit to this group, either to patients or caregivers. The review covered 7 studies, involving 1913 patients. The longest study lasted 28 weeks. The main problem was a lack of reliable evidence, and a lack of studies of longer duration, as well as a lack of research with relevant patient groups.

http://www.eurekalert.org/pub_releases/2009-10/ifqa-bom102809.php

Memantine works differently than thought

New research shows that the drug memantine, praised as "the first and only representative of a new class of Alzheimer drugs", in fact works similar to other existing compounds, and although the data do confirm that memantine shows promising aspects for the treatment of Alzheimer’s, this is only in a narrow concentration range. Its complex pharmacological profile requires careful considerations concerning suitable doses and suitable patient groups.

Drever, B.D. et al. 2007. Memantine acts as a cholinergic stimulant in the mouse hippocampus. Journal of Alzheimer's Disease, 12 (4), 319-333.

http://www.eurekalert.org/pub_releases/2008-01/ip-maa011008.php

Some benefit from memantine for moderate-to-severe Alzheimer’s

A review of nine published studies comprising 2,339 participants has concluded that memantine has a small but significant cognitive benefit for moderate-to-severe Alzheimer’s patients. It also seems to prevent the onset of agitation. Although there was some indication of benefit for those with mild to moderate Alzheimer’s, the effects were not significant. Researchers caution that the drug treats the symptoms only, slowing the progress of the disease only.

Sastre, A. Areosa et al. 2005. Memantine for dementia. The Cochrane Database of Systematic Reviews, Issue 2.

http://www.eurekalert.org/pub_releases/2005-04/cfta-sap041505.php

New drug approved for moderate to severe Alzheimer's

The FDA recently approved memantine for treatment of moderate to severe Alzheimer’s. The drug has been used for some 20 years in Germany. While memantine significantly improved performance in Alzheimer’s sufferers in studies, the effect, as with all Alzheimer’s drugs currently in use, is small.

Tariot, P.N., Farlow, M.R., Grossberg, G.T., Graham, S.M., McDonald, S. & Gergel, I. 2004. Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: A randomized controlled trial. JAMA, 291, 317-24.

http://www.eurekalert.org/pub_releases/2004-01/uorm-jsc012004.php
http://www.eurekalert.org/pub_releases/2004-01/jaaj-ndi011504.php

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

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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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Unmet needs among those living at home with dementia

A study involving 254 people with dementia living at home has found that 99% of people with dementia and 97% of their caregivers had one or more unmet needs, 90% of which were safety-related. More than half of the patients had inadequate meaningful daily activities at a senior center or at home, one-third still needed a dementia evaluation or diagnosis, and more than 60% needed medical care for conditions related or unrelated to their dementia.

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Prion proteins might help reduce amyloid-beta plaques

New research helps explain the role of amyloid-beta plaques in the development of Alzheimer's, by finding that the prion protein known to bind strongly to small aggregates of amyloid-beta peptides, also attaches to large fibrillar clumps of amyloid-beta.

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Shift away from glycemic control in diabetes treatment

It is now realized that the focus in treating diabetes shouldn’t be so much on controlling blood sugar. New medical guidelines point to the importance of the following interventions (in order of benefit):

  1. smoking cessation (most important)
  2. blood pressure control
  3. metformin drug therapy
  4. lipid reduction
  5. glycemic control (least important).

This isn’t to say that blood sugar isn’t important; but the others should be dealt with first.

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Cancer drug not fully confirmed for Alzheimer's treatment

Last year, a cancer drug, Bexarotene, was touted as a potential treatment for Alzheimer’s disease. However, four independent studies have now failed to replicate the most dramatic result of the original study: a claim that the drug could clear half the amyloid plaques in a mere 72 hours.

Still, two of the studies confirmed findings that the drug reduced levels of amyloid-beta, and one showed improved cognition in mice.

The inconsistencies suggest more research is needed. The drug is now being tested in humans.

05/2013

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