Alzheimers

Alzheimer's & other dementias

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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How the Alzheimer’s gene increases risk

We know that the E4 variant of the APOE gene greatly increases the risk of developing Alzheimer’s disease, but the reason is a little more mysterious. It has been thought that it makes it easier for amyloid plaques to form because it produces a protein that binds to amyloid beta.

05/2013

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High blood sugar may raise Alzheimer’s risk

I’ve talked before about the evidence linking diabetes to an increased risk of Alzheimer’s disease, but now a new study suggests that elevated blood sugar levels increase Alzheimer’s risk even in those without diabetes, even in those without ‘pre-diabetes’.

05/2013

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Gene doubles Alzheimer’s risk in African Americans

A study involving nearly 6,000 African American older adults has found those with a specific gene variant have almost double the risk of developing late-onset Alzheimer’s disease compared with African Americans who lack the variant. The size of the effect is comparable to that of the ‘Alzheimer’s gene’, APOE-e4.

04/2013

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Alzheimer's Treatment - Neurological & surgical interventions

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

Gene Therapy

Targeting a key enzyme with gene therapy reversed course of Alzheimer's disease in mouse models

A study using genetically engineered mice has reversed the rats' memory loss by silencing a gene that helps produce amyloid plaques. The size and number of plaques were reduced by two-thirds within a month.

Singer, O. et al. 2005. Targeting BACE1 with siRNAs ameliorates Alzheimer disease neuropathology in a transgenic model. Nature Neuroscience, 8, 1343-1349.

http://www.eurekalert.org/pub_releases/2005-09/si-tak092005.php

Gene therapy slows cognitive decline in trial

The first human clinical trial of gene therapy for Alzheimer’s, involving 8 volunteers, has found an increase in the brain’s use of glucose — a sign of brain activity — and a significant slowing of the patients’ rate of cognitive decline in the 6 patients who completed the procedure safely.

Tuszynski, M.H. et al. 2005. A phase 1 clinical trial of nerve growth factor gene therapy for Alzheimer disease. Nature Medicine, 11(5), 551-555.

http://www.eurekalert.org/pub_releases/2005-04/uoc--acd041805.php

New gene therapy technique

A new technique using gene therapy to deliver nerve growth factor into regions of the brain where neurons are degenerating is being trialed in a two-year study. The technique, which requires neurosurgery to inject the drug precisely where it is required (the basal forebrain), uses a new drug called CERE-110. Extensive studies in several animal models, including primates, have showed that NGF gene delivery to the basal forebrain prevented the death of cholinergic neurons (which undergo severe degeneration and death in Alzheimer's disease patients).

http://www.eurekalert.org/pub_releases/2004-09/rpsl-seg092004.php

Preliminary results promising in Alzheimer's gene therapy trial

A small, preliminary study has had some success in delaying brain cell loss in early Alzheimer’s patients through the surgical placement of genetically modified tissue directly into their brains.

The study was reported on April 27 at the American Academy of Neurology meeting in San Francisco.

http://www.eurekalert.org/pub_releases/2004-04/uoc--pra042204.php

UCSD team performs first surgery in gene therapy protocol for Alzheimer's disease

In a groundbreaking procedure, physicians at the University of California, San Diego (UCSD) School of Medicine have surgically implanted genetically modified tissue into the brain of an Alzheimer's patient. This launches the first phase of an experimental gene therapy protocol for Alzheimer's disease. The therapy delivers a natural molecule called nerve growth factor (NGF) to the dying cells in the brain.
If the protocol is successful, implanted cells could begin to affect brain function in a month or two, but Tuszynski cautions that "it may take several years to test the procedure in a large enough number of patients to determine whether it will be useful therapy." The therapy is not expected to cure Alzheimer's disease, but it may restore some brain cells and alleviate symptoms such as short-term memory loss for several years.

Conner, J. M., Darracq, M. A., Roberts, J., & Tuszynski, M. H. (2001). Nontropic actions of neurotrophins: Subcortical nerve growth factor gene delivery reverses age-related degeneration of primate cortical cholinergic innervation. Proceedings of the National Academy of Sciences, 98(4), 1941–1946. doi:10.1073/pnas.98.4.1941

http://www.eurekalert.org/pub_releases/2001-04/UNKN-Utpf-0904101.php

CSF shunt

Draining toxins from cerebrospinal fluid stabilizes cognitive decline

The ever-slowing capacity to clear the build-up of such toxins as isoprostanes and misfolded proteins that accumulate in the brains of Alzheimer's disease patients causes the death of cells involved in memory and language. A preliminary study has shown that reducing the levels of isoprostanes by draining cerebral spinal fluid can stave off future reductions in cognitive abilities. Cognitive scores in the 8 patients receiving the treatment were stable after one year, while scores in those not receiving the treatment declined 20%. The next phase of the study involves nearly 100 patients.

Praticò, D., Yao, Y., Rokach, J., Mayo, M., Silverberg, G.G. & McGuire, D. 2004. Reduction of brain lipid peroxidation by CSF drainage in Alzheimer’s disease patients. Journal of Alzheimer's Disease, 6(4), 385-389.

http://www.eurekalert.org/pub_releases/2004-08/uopm-dti082004.php

Can Alzheimer's disease be slowed by shunting cerebrospinal fluid?

A pilot study has tested the hypothesis that improving cerebrospinal fluid (CSF) turnover will slow or stop the progression of dementia in people with Alzheimer's disease. CSF shunting for dementia, described in 1969, was largely abandoned due to mixed clinical results and an unacceptably high incidence of adverse events. However recent clinical studies in which CSF shunting was used to treat patients with symptomatic hydrocephalus demonstrated a coincidental lack of cognitive decline in patients who also had Alzheimer's dementia. A pilot study has found Alzheimer's patients who were shunted experienced relative stability while the control group demonstrated a fairly robust decline in cognitive function over the 12 months of the study. A larger, multi-center, controlled clinical trial is now underway.

Silverberg, G.D., Levinthal, E., Sullivan, E.V., Bloch, D.A., Chang, S.D., Leverenz, J., Flitman, S., Winn, R., Marciano, F., Saul, T., Huhn, S., Mayo, M. & McGuire, D. 2002. Assessment of low-flow CSF drainage as a treatment for AD: Results of a randomized pilot study. Neurology, 59, 1139-1145.

http://www.eurekalert.org/pub_releases/2002-10/aaon-cad101502.php

Possible new surgical treatment

An 18-month, double-blind placebo study into a new surgical treatment for Alzheimer’s disease using a device called the COGNIShunt, is being undertaken by neurologists at Emory University. The shunt is designed to drain cerebrospinal fluid (CSF) from the skull and into the abdominal cavity. By reducing the build-up of CSF around the brain, doctors hope this device will help to stabilize the disease. In a pilot study of the COGNIShunt, the device was well tolerated by individuals with mild to moderate Alzheimer’s disease.

http://www.eurekalert.org/pub_releases/2002-03/euhs-esc032102.php

Animal studies

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

Neural stem cells offer potential treatment for Alzheimer's

Genetically engineered mice performed markedly better on memory tests a month after neural stem cells were injected into their Alzheimer-like brains. The stem cells secreted a protein that created more neural connections, improving cognitive function. Surprisingly, only 6% of the stem cells became neurons (most became ‘support cells’: astrocytes and oligodendrocytes). The benefit of stem cells seemed rather to lie in their secretion of BDNF, which encouraged the formation of new synapses. The direct injection of BDNF also had cognitive benefit, but not as much as with the neural stem cells, which provided a more long-term and consistent supply of the protein.

Norton, M.C. et al. 2009. Caregiver–Recipient Closeness and Symptom Progression in Alzheimer Disease. The Cache County Dementia Progression Study. The Journals of Gerontology Series B: Psychological Sciences and Social Sciences, Advance Access published on June 29, 2009. Full text available at http://www.pnas.org/content/106/32/13594.abstract

http://www.eurekalert.org/pub_releases/2009-07/uoc--nsc072009.php

Growth factor protects key brain cells in Alzheimer's models

In a series of cell culture and animal studies, involving genetically engineered mice, rats, and rhesus monkeys, injections of brain-derived neurotrophic factor (BDNF) resulted in significant improvement in brain functioning and on learning and memory tests. The growth factor, important for neurogenesis, is normally produced in the entorhinal cortex, an area damaged early in Alzheimer’s disease.

Nagahara, A.H. et al. 2009. Neuroprotective effects of brain-derived neurotrophic factor in rodent and primate models of Alzheimer's disease. Nature Medicine, 15, 331–337.

http://www.eurekalert.org/pub_releases/2009-02/uoc--gfp020309.php

Inhibitor of amyloid-beta clearing enzyme found

A new way of destroying amyloid-beta proteins has been found. Following previous research showing that the enzyme cathepsin B destroys the protein, scientists have now succeeded in increasing the activity of the enzyme by reducing the activity of the protease inhibitors cystatin C, the enzyme’s natural inhibitor. In mice, this had the effect of improving memory and extending life.

Sun, B. et al. 2008. Cystatin C-Cathepsin B Axis Regulates Amyloid Beta Levels and Associated Neuronal Deficits in an Animal Model of Alzheimer's Disease. Neuron, 60 (2), 247-257.

http://www.eurekalert.org/pub_releases/2008-10/gi-gsf102008.php

New way to target Alzheimer's disease

In a series of studies in transgenic mice, a synthetic peptide designed to block the interaction between apolipoprotein E and amyloid-beta protein reduced the aggregation of toxic amyloid protein in the brain by around 50%. The treated mice showed no memory decline.

Sadowski, M.J. et al. 2006. Blocking the apolipoprotein E/amyloid- interaction as a potential therapeutic approach for Alzheimer's disease. Proceedings of the National Academy of Sciences, 103, 18787-18792. The full text is available at http://www.pnas.org/cgi/content/full/103/49/18787

http://www.eurekalert.org/pub_releases/2006-12/nyum-sda120406.php

Androgen therapy may slow progress of Alzheimer's disease

Recent studies have suggested a link between testosterone loss in men and Alzheimer’s. A new study has now found a correlation between low testosterone and elevated beta-amyloid, providing more support that testosterone depletion in aging men increases the risk of Alzheimer’s. Testosterone belongs to a group of steroid hormones called androgens. The mouse study found that androgen therapy was successful in preventing beta-amyloid accumulation and cognitive decline in castrated mice.

Rosario, E.R. et al. 2006. Androgens Regulate the Development of Neuropathology in a Triple Transgenic Mouse Model of Alzheimer's Disease. Journal of Neuroscience, 26, 13384-13389.

http://www.eurekalert.org/pub_releases/2006-12/sfn-tm121906.php

Insulin receptor stops progression of Alzheimer's

Following previous research suggesting Alzheimer's might be a brain-specific neuroendocrine disorder, or a Type 3 diabetes, a new study has found that stimulation of a receptor in the brain that controls insulin responses prevents several components of neurodegeneration and preserves learning and memory in rats with induced Alzheimer's disease, raising the possibility that patients in the very early stages of Alzheimer’s might be treatable.

de la Monte, S.M. et al. 2006. Therapeutic rescue of neurodegeneration in experimental type 3 diabetes: relevance to Alzheimer’s disease. Journal of Alzheimer's Disease, 10 (1), 89-109.

http://www.eurekalert.org/pub_releases/2006-09/l-irs092106.php

Brain enzyme treatment for Alzheimer's

In a new approach to treating Alzheimer’s, increasing brain levels of ubiquitin C-terminal hydrolase L1 (Uch-L1) — an enzyme that helps neurons rid themselves of excess or aberrant proteins — has restored a great deal of brain activity to mice with Alzheimer's symptoms. The enzyme Uch-L1 is part of a network that controls a memory molecule called CREB, which is inhibited by amyloid beta proteins in people with Alzheimer's. Uch-L1 is found at reduced levels in the Alzheimer's brain. As well as improving memory in genetically engineered mice, treatments that restored Uch-L1 levels corrected deficits in nerve transmission both in brain slices treated with amyloid-beta and in slices taken from transgenic mice.

Gong, B. et al. 2006. Ubiquitin Hydrolase Uch-L1 Rescues B-Amyloid-Induced Decreases in Synaptic Function and Contextual Memory. Cell, 126, 775–788.

http://www.eurekalert.org/pub_releases/2006-08/cp-bet082106.php
http://www.eurekalert.org/pub_releases/2006-08/cumc-crr082206.php

Why chances of Alzheimer's increase with age

Experiments with roundworms have revealed two important proteins that help slow down the accumulation of amyloid-beta. HSF-1 breaks apart amyloid and disposes of it — but aging slows HSF-1, so it can't keep up. DAF-16 helps it out, by clumping extra amyloid together in a way that makes it less toxic. The finding supports recent research indicating amyloid clumps, or plaques, are not the main problem, rather, smaller amyloid tendrils inside cells are. The study also explains why aging increases the likelihood of Alzheimer’s. Most importantly of all, it suggests a new approach to treating Alzheimer’s.

Cohen, E. et al. 2006. Opposing Activities Protect Against Age-Onset Proteotoxicity. Science, 313 (5793), 1604–1610.

http://www.msnbc.msn.com/id/14290153/
http://www.boston.com/news/nation/articles/2006/08/11/scientists_find_natural_alzheimers_controls/

Potential new treatment strategy for Alzheimer's

A study has identified several new compounds that could play a role in preventing or treating Alzheimer's disease and other degenerative conditions of the nervous system. In culture, these compounds bind with a receptor called p75NTR; a receptor that in the body binds neurotrophins. There is some evidence that in Alzheimer's, some of the neurons that die express the p75NTR binding site, indicating they may be dying because neurotrophins are binding to them. Because the new compounds bind with p75NTR in place of neurotrophins, they may provide a means of preventing damage that neurotrophins would otherwise be causing. The compounds were also found to inhibit the death of oligodendrocytes.

Massa, S.M. et al. 2006. Small, Nonpeptide p75NTR Ligands Induce Survival Signaling and Inhibit proNGF-Induced Death. Journal of Neuroscience, 26, 5288-5300.

http://www.eurekalert.org/pub_releases/2006-05/uoc--pnt051706.php

Memory loss in genetically engineered mice reversed

Mice were genetically engineered to develop dementia; the transgene was designed to be able to be turned off. The researchers expected that when the transgene expressing the dementia was turned off, memory loss would stop. Instead, they were surprised to find the loss was reversed; the mice regained their memory. A further surprise occurred when it was found that the neurofibrillary tangles, thought to be one of the causes of dementia, remained, and even increased, suggesting that the tangles are not a cause of dementia.

SantaCruz, K. et al. 2005. Tau Suppression in a Neurodegenerative Mouse Model Improves Memory Function, Science, 309 (5733), 476-481.

http://www.eurekalert.org/pub_releases/2005-07/uom-uom071105.php

Inhibiting Apolipoprotein E possible means of therapeutic intervention

It has been known that the inflammatory protein ApoE can speed the buildup in the brain of amyloid plaques,but the mechanism has not been known. A mouse study found ApoE is responsible for converting harmless amyloid-beta into the toxic fibrous deposits known as filamentous amyloid. This process is needed to damage nerve cells in parts of the brain controlling memory and cognition. Mice with Alzheimer's disease showed memory deficits only when the ApoE gene was present. The study suggests that preventing ApoE from acting upon amyloid-beta may prove to be an effective means of therapeutic intervention.

Costa, D.A., Nilsson, L.N.G., Bales, K.R., Paul, S.M. & Potter, H. 2004. Apolipoprotein E is required for the formation of filamentous amyloid but not for amorphous AB deposition, in an Aâ PP/PS double transgenic mouse model of Alzheimer's disease. Journal of Alzheimer's Disease, 6, 509–514.

Nilsson, L.N.G., Arendash, G.W., Leighty, R.E., Costa, D.A., Garcia, M.F., Cracciola, J.R., Rojiani, A., Wu, X., Bales, K.R., Paul, S.M. & Potter, H. 2004. Cognitive impairment in PDAPP mice depends on ApoE and ACT-catalyzed amyloid. Neurobiology of Aging, 25 (9), 1153-1167.

http://www.eurekalert.org/pub_releases/2004-10/uosf-rur102904.php

Researchers identify brain protein that halts progression of Alzheimer's

Researchers have identified a protein in the brain, "transthyretin," that halts the progression of Alzheimer's disease in human brain tissue by blocking beta-amyloid.

The findings were presented on October 26 at the 34th annual meeting of the Society for Neuroscience in San Diego, Calif.

http://www.eurekalert.org/pub_releases/2004-10/nioe-rib102504.php

Early clinical treatment can halt progression of Alzheimer's disease

A study using genetically engineered mice has provided evidence that early clinical treatment of brain lesions (by injecting anti-beta-amyloid antibodies into the hippocampus) can halt the progression of Alzheimer's disease. The clearance of amyloid plaques led to the clearance of the lesions caused by neurofibrillary tangles. The effect on neurofibrillary tangles only occurs, however, if done at a particular stage of the tangle’s growth — the earlier the treatment begins, therefore, the better the chance of success. The demonstration that early treatment of amyloid plaques stops the progression of Alzheimer’s provides support for the controversial theory that the accumulation of amyloid plaques is the initiating trigger of the disease process.

Oddo, S., Billings, L., Kesslak, P., Cribbs, D.H. & LaFerla, F.M. 2004. Aβ Immunotherapy Leads to Clearance of Early, but Not Late, Hyperphosphorylated Tau Aggregates via the Proteasome. Neuron, 43, 321-332.

http://www.eurekalert.org/pub_releases/2004-08/uoc--ect072804.php

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

A new approach to slowing the progression of Alzheimer’s

Researchers have discovered the molecules that play a critical role in making the brain think it is under attack from the amyloid plaques characteristic of Alzheimer’s disease. Microglial cells detect beta amyloid plaques and gear up to fight them as foreign invaders. However, for some unknown reason, they don’t follow through on the attack, but remain inflamed. It is this inflammation that causes a lot of the problem. Research has now shown that the microglial cells at least four different receptor proteins to bind to the amyloid. Each one of these receptor proteins act together at the same time to drive the inflammation. This discovery suggests a new approach to treating Alzheimer’s — finding a means to block these receptors.

Bamberger, M.E., Harris, M.E., McDonald, D.R., Husemann, J. & Landreth, G.E. 2003. A Cell Surface Receptor Complex for Fibrillar b-Amyloid Mediates Microglial Activation. Journal of Neuroscience, 23, 2665-2674.

http://www.eurekalert.org/pub_releases/2003-04/cwru-mti042903.php

Gene transfer reduces levels of key Alzheimer's disease protein

An animal study has found that a molecule that naturally degrades of the protein beta-amyloid (the substance in the amyloid plaques indicative of Alzheimer’s) appears to reduce the levels of that protein by nearly 50% when delivered by gene therapy.

Marr, R.A., Rockenstein, E., Mukherjee, A., Kindy, M.S., Hersh, L.B., Gage, F.H., Verma, I.M. & Masliah, E. 2003. Neprilysin Gene Transfer Reduces Human Amyloid Pathology in Transgenic Mice. Journal of Neuroscience, 23, 1992-1996.

http://www.eurekalert.org/pub_releases/2003-03/si-gtr032003.php

Growth factor creates new neurons; may aid treatment of neurological diseases

In a series of studies, a growth factor (BDNF) was introduced into the adult rat brain, and was found to produce new neurons in various brain regions. BDNF is reduced in parts of the brain of those with Huntington’s disease and Alzheimer’s disease. These studies indicate that supplementing the adult brain with BDNF not only supports neurons in those brains, but also induces new neurons from precursor cells.

Pencea, V., Bingaman, K. D., Wiegand, S. J., & Luskin, M. B. (2001). Infusion of Brain-Derived Neurotrophic Factor into the Lateral Ventricle of the Adult Rat Leads to New Neurons in the Parenchyma of the Striatum, Septum, Thalamus, and Hypothalamus. The Journal of Neuroscience, 21(17), 6706–6717. Retrieved from http://www.jneurosci.org/content/21/17/6706

Benraiss, A., Chmielnicki, E., Lerner, K., Roh, D., & Goldman, S. A. (2001). Adenoviral Brain-Derived Neurotrophic Factor Induces Both Neostriatal and Olfactory Neuronal Recruitment from Endogenous Progenitor Cells in the Adult Forebrain. The Journal of Neuroscience, 21(17), 6718–6731. Retrieved from http://www.jneurosci.org/content/21/17/6718

http://www.eurekalert.org/pub_releases/2001-08/sfn-nnm083101.php

Transplanted human neural stem cells improve memory in rats

Laboratory-grown human neural stem cells, the building blocks of the brain, were successfully transplanted for the first time into the brains of aged rats and dramatically improved the animals' cognitive function. The results of the study could lay the foundation for new treatments in diseases such as Alzheimer's and Parkinson's.
Neural cell transplant studies recently suffered a setback when transplanted fetal cells worsened symptoms in Parkinson's patients. However, such fetal cells are already differentiated. Laboratory-grown stem cells are not differentiated, allowing the host brain to take over, dictating where the stem cells should migrate and what types of cells they should become. As a result, the transplanted cells became functionally integrated into the neuronal circuitry of the host animal. Postmortem examination of the rats' brains demonstrated that the transplanted human brain cells had not only differentiated and were thriving in the new environment, but that the rats' own neuronal fibers had grown dramatically in areas associated with spatial memory.

Qu,T, Brannen, C.L., Kim, H.M., & Sugay, K. (n.d.). Human neural stem cells improve cognitive function of aged brain. Retrieved 27 April 2013, from http://journals.lww.com/neuroreport/Fulltext/2001/05080/Human_neural_ste...

http://www.eurekalert.org/pub_releases/2001-04/UoIa-Thns-2304101.php

tags development: 

tags problems: 

Alzheimer's: Diagnosis & Assessment

Separate pages for

Early Markers

Cognitive Tests

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

Diagnosis & assessment

Dementia often undiagnosed

A study involving 553 patients of 34 primary care physicians affiliated with three Portland-area managed health care plans has confirmed previous research finding that many older patients showing signs of dementia are not being diagnosed. The study found that only 18% of mildly impaired patients and 34.8% of moderately-to-severely impaired patients were clinically evaluated for dementia, and that none of the mildly impaired patients and just 4.3% of the more severely impaired patients were offered dementia medication.

Boise, L., Neal, M. B., & Kaye, J. (2004). Dementia Assessment in Primary Care: Results From a Study in Three Managed Care Systems. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 59(6), M621–M626. doi:10.1093/gerona/59.6.M621

http://www.eurekalert.org/pub_releases/2004-07/ohs-sdo071504.php

Life expectancy following diagnosis of Alzheimer’s depends on age at diagnosis

A new study reveals that the life span of people with Alzheimer's disease depends greatly on the age of the person when Alzheimer's disease is diagnosed. The study indicates that the median survival of patients with Alzheimer's disease could range from 8.3 years for those diagnosed at age 65 to 3.4 years for those diagnosed at age 90. There were no significant differences between men and women. The average length of time between the onset of symptoms and the diagnosis of Alzheimer's was 2.8 years.

Brookmeyer, R., Corrada, M.M., Curriero, F.C. & Kawas, C. 2002. Survival Following Diagnosis of Alzheimer Disease, Archives of Neurology, 59, 1764-1767.

http://www.eurekalert.org/pub_releases/2002-11/jhub-lef111502.php

New tests

Biomarker signatures predict conversion from MCI to Alzheimer's

Cerebrospinal fluid samples from 410 volunteers (100 with mild Alzheimer’s; 196 with MCI; 114 cognitively normal older adults) has revealed that concentrations of amyloid beta-42 peptide and tau protein successfully assessed brain status and predicted development. The test diagnosed Alzheimer’s with 96% accuracy; ruled out Alzheimer’s with 95% accuracy; and predicted the conversion from MCI to Alzheimer’s with 82% accuracy.

Shaw, L.M. et al. 2009. Cerebrospinal fluid biomarker signature in Alzheimer's disease neuroimaging initiative subjects. Annals of Neurology, Published Online March 18 2009.

http://www.eurekalert.org/pub_releases/2009-03/uops-pmp031609.php

Computers better at diagnosing Alzheimer's

A new method has been developed that allows a standard computer to spot the differences between brain scans from patients with proven Alzheimer’s disease and people with no signs of the disease at all. The accuracy is better than the 86% correct diagnostic rate of best clinical practice. The method was also better at distinguishing Alzheimer’s from fronto-temporal dementia. The findings may help ensure that patients are diagnosed earlier, increasing treatment options.

Klöppel, S. et al 2008. Automatic classification of MR scans in Alzheimer's disease. Brain, 131, 681-689.

http://www.eurekalert.org/pub_releases/2008-02/wt-ccb022108.php

Portable device quickly detects early Alzheimer's

A new device may allow patients to take a brief, inexpensive test that could be administered as part of a routine yearly checkup at a doctor’s office to detect mild cognitive impairment (MCI) — often the earliest stage of Alzheimer’s. The device, called DETECT, takes about ten minutes to run through a battery of visual and auditory stimuli such as pictures and words that assess cognitive abilities relative to age, gauging reaction time and memory capabilities. Its software can track cognitive capabilities year to year during annual appointments. Moreover, because the device blocks outside sound and light from the patient’s environment, it can be administered in virtually any setting, providing more consistent results. Preliminary analysis gives the test similar accuracy to the 90-minute “Gold Standard” pen and paper test. The device is expected to be commercialized later this year.

http://www.eurekalert.org/pub_releases/2008-01/giot-pdq011608.php

New diagnostic criteria for Alzheimer's disease

An international group of Alzheimer’s disease (AD) experts have proposed new diagnostic criteria for Alzheimer’s. The existing criteria were published in 1984. To meet the new criteria for probable AD, patients must show progressive memory loss over more than six months, plus at least one or more of the supportive biomarker criteria. These include: atrophy in a particular part of the brain shown by MRI, abnormal biomarker proteins in the cerebrospinal fluid, a specific pattern on PET of the brain, and a genetic mutation for AD within the immediate family.

Dubois, B. et al. 2007. Research criteria for the diagnosis of Alzheimer's disease: revising the NINCDS–ADRDA criteria. Lancet Neurology, 6, 734-746.

http://www.eurekalert.org/pub_releases/2007-07/l-ndc070607.php

Protein 'fingerprint' in spinal fluid could spot Alzheimer's disease early

In a pilot study, a panel of 23 protein biomarkers in cerebrospinal fluid has been found to be over 90% sensitive in identifying people with Alzheimer's disease.

Finehout, E.J. et al. 2006. Cerebrospinal fluid proteomic biomarkers for Alzheimer's disease (pNA). Annals of Neurology, published online ahead of print December 13

http://www.eurekalert.org/pub_releases/2006-12/cuns-pi120706.php

New reliable test for Alzheimer's

A new test for Alzheimer’s promises a reliable means of diagnosing Alzheimer’s in a living patient. Combined with clinical assessment, testing blood flow in a specific region of the brain may boost the degree of diagnostic certainty in difficult cases from 90% to almost 100%. The test involves use of single-photon emission computed tomography (SPECT) — a radioisotope test that produces a three-dimensional picture of the amount of blood flowing in certain regions of the brain — to identify a characteristic sign of Alzheimer's disease (reduced blood flow in the posterior cingulate cortex) and distinguish it from a group of illnesses known as frontotemporal diseases, which comprise the second-leading cause of dementia in the elderly. The test did fail to identify Alzheimer’s patients with an atypical form of Alzheimer’s known as tangle-predominant AD. This form of Alzheimer’s also appears to be resistant to drugs currently used to help treat Alzheimer’s. Evidence of shrinkage in brain structures such as the hippocampus and parietal cortex is also central to diagnosing Alzheimer's. This atrophy can be seen on a standard MRI.

Bonte, F.J., Harris, T.S., Roney, C.A. & Hynan, L.S. 2004. Differential Diagnosis Between Alzheimer's and Frontotemporal Disease by the Posterior Cingulate Sign. Journal of Nuclear Medicine, 45 (5), 771-4.

http://www.eurekalert.org/pub_releases/2004-05/uots-rin050404.php
http://www.eurekalert.org/pub_releases/2004-05/sonm-sis050504.php

New diagnostic marker for Alzheimer's disease

A mouse study has unexpectedly revealed that a protein that senses changes in calcium levels can be used to estimate the extent of cognitive deficits caused by toxic amyloid peptides found in Alzheimer brains. The discovery came about when researchers found that those mice with learning and memory deficits had not only the expected high level of amyloid peptides in their brains, but also had very low levels of a protein called calbindin that binds calcium and regulates functions in granule cells, located in the dentate gyrus (a region that plays an important role in memory formation). Examination of autopsy brain tissue from Alzheimer sufferers has confirmed this finding. It is hoped that this will prove a valuable diagnostic marker.

Palop, J.J. et al. 2003. Neuronal depletion of calcium-dependent proteins in the dentate gyrus is tightly linked to Alzheimer's disease-related cognitive deficits. PNAS, 100, 9572-9577.

http://www.eurekalert.org/pub_releases/2003-07/uoc--bcs071003.php

A new portable device might be able to screen for Alzheimer's

NeuroGraph™, a portable device that provides an almost instantaneous reading of brain activity and can swiftly detect differences from the norm, offers enormous commercial potential as a screening device for Alzheimer’s disease. It might also be useful in pharmaceutical trials, to test the efficacy of new drugs on brain activity against drugs already on the market.

http://www.eurekalert.org/pub_releases/2001-09/oonr-da091901.php

New home-safety assessment scale for people with dementia living at home

A pan-Canadian team of researchers designed, tested and validated the first "Home-safety Assessment Scale for People with Dementia Living at Home" (S.A.S.). The SAS has been tested and validated among 175 patients in English and French, in both urban and rural areas. "Thanks to the SAS, physicians, nurses, family helpers, social workers, physiotherapists and occupational therapists can now evaluate in a few minutes the risks of accidents in any particular home."

http://www.eurekalert.org/pub_releases/2001-09/mu-nha091401.php

Diagnosing Alzheimer's

It is not always easy for doctors to know whether a patient is suffering from Alzheimer's disease or some other form of dementia. A new study suggests tracking a patient's circadian rhythm (the daily cycle of body temperature change and activity) may lead not only to better diagnosis but also to better therapy for the devastating sleep disturbances that often accompany dementia. The study looked at the circadian rhythms of 38 dementia patients over six years. Some had Alzheimer's; others had what is known as fronto-temporal degeneration. Patients with Alzheimer's reached their temperature peak much later in the day than healthy people. People with fronto-temporal dementia had a normal temperature rhythm, but their activity levels peaked much earlier compared with levels of healthy people. And while people with fronto-temporal degeneration did have restful periods, these were much rarer with Alzheimer's. Their work, the researchers said, may help doctors who have tried to treat insomnia in dementia patients with melatonin and light therapy, in an effort to "reset" their biological clocks.

Harch, P. G., Kriedt, C., Van Meter, K. W., & Sutherland, R. J. (2007). Hyperbaric oxygen therapy improves spatial learning and memory in a rat model of chronic traumatic brain injury. Brain Research, 1174, 120–129. doi:10.1016/j.brainres.2007.06.105

http://www.nytimes.com/2001/04/17/health/17VITA-5.html

New guidelines for diagnosis and treatment of Alzheimer's

Experts reviewed more than a thousand studies to develop new guidelines for physicians for diagnosis and treatment of Alzheimer's. The recommendations include topics ranging from how to recognize early signs of Alzheimer's, how to diagnose, when medication is most effective and what types of support can improve the quality of life for patients and caregivers.
"It's important to remember there are choices available that can make a difference in your life or the life of your husband, grandmother, neighbor or anyone you care about who has Alzheimer's disease," said neurologist Steven DeKosky, MD, co-author of the guidelines. Early diagnosis is important because research shows current medication and care options are most effective in people with mild to moderate Alzheimer's disease. While Alzheimer's disease has no cure, medication can improve quality of life and cognitive functions–including memory, thought and reasoning– particularly among people who are mildly to moderately affected. Regular routines and activities such as mild exercise or walking can help with behavioral symptoms. In addition, education and support for caregivers can improve the well-being of both the person with Alzheimer's disease and the caregiver.
While the comprehensive guidelines were developed for physician use, a summary is available to help patients and their families better understand the options to discuss with their doctor.

Petersen, R. C., Stevens, J. C., Ganguli, M., Tangalos, E. G., Cummings, J. L., & DeKosky, S. T. (2001). Practice parameter: Early detection of dementia: Mild cognitive impairment (an evidence-based review) Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology, 56(9), 1133–1142. doi:10.1212/WNL.56.9.1133

Knopman, D. S., DeKosky, S. T., Cummings, J. L., Chui, H., Corey–Bloom, J., Relkin, N., … Stevens, J. C. (2001). Practice parameter: Diagnosis of dementia (an evidence-based review) Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology, 56(9), 1143–1153. doi:10.1212/WNL.56.9.1143

Doody, R. S., Stevens, J. C., Beck, C., Dubinsky, R. M., Kaye, J. A., Gwyther, L., … Cummings, J. L. (2001). Practice parameter: Management of dementia (an evidence-based review) Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology, 56(9), 1154–1166. doi:10.1212/WNL.56.9.1154

http://www.eurekalert.org/pub_releases/2001-05/AAoN-Ngee-0605101.php

Scans

PET scans may improve accuracy of dementia diagnosis

A study involving 66 patients with mild dementia or mild cognitive impairment, who were diagnosed with either Alzheimer's disease, frontotemporal dementia or dementia with Lewy bodies, by three specialists, had these diagnoses changed more than 25% of the time after PET imaging. The findings point to the importance of using PET scans to accurately diagnose the type of dementia.

Frey, K. et al. 2009. PET neurochemical vs. clinical phenotypes in mild-early dementia. Presented at the SNM's 56th Annual Meeting, June 13-17, 2009. Scientific Paper 251.

http://www.eurekalert.org/pub_releases/2009-06/sonm-psm061409.php

Technique shows brain aging before symptoms appear

A new chemical marker called FDDNP, which binds to plaque and tangle deposits in the brain, has enabled PET scans to reveal exactly where these abnormal protein deposits are accumulating, and has found that older age correlated with higher concentrations of FDDNP in the medial and lateral temporal regions of the brain, areas involved with memory, where plaques and tangles usually collect. Of the 76 study volunteers, 34 carried the ‘Alzheimer’s gene’. This group demonstrated higher FDDNP levels in the frontal region of the brain than those without the gene variant. Thirty-six of the volunteers had mild cognitive impairment, and these had higher measures of FDDNP in the medial temporal brain regions than normal volunteers. Those who had both MCI and the APOE-4 gene also had higher concentrations of FDDNP in the medial temporal brain regions than those who had MCI but not APOE-4. The pilot study offers hope of early diagnosis of brain impairment, before symptoms show themselves.

Small, G.W. et al. 2009. Influence of Cognitive Status, Age, and APOE-4 Genetic Risk on Brain FDDNP Positron-Emission Tomography Imaging in Persons Without Dementia. Archives of General Psychiatry, 66(1), 81-87.

http://www.eurekalert.org/pub_releases/2009-01/uoc--uat010509.php

MRI brain scans accurate in early diagnosis of Alzheimer's disease

Adding to the growing body of evidence indicating MRI brain scans provide valuable diagnostic information about Alzheimer's disease, a study in which a new visual rating system for evaluating the severity of shrinkage in the medial temporal lobe was used on brain scans of 260 people has found that scores accurately distinguished those with Alzheimer’s from those with mild cognitive impairment and those without memory problems. The test also accurately predicted those who would move from one group to another within a year or two.

Duara, R. et al. 2008. Medial temporal lobe atrophy on MRI scans and the diagnosis of Alzheimer disease. Neurology, 71, 1986-1992.

http://www.eurekalert.org/pub_releases/2008-12/uosf-mbs121808.php

Study validates Pittsburgh Compound-B in identifying Alzheimer's disease toxins

Previous research demonstrating that Pittsburgh Compound-B (PiB) binds to beta-amyloid deposits has involved only the autopsied brains of patients afflicted with Alzheimer’s. A new study correlated PiB-identified beta-amyloid deposits in a living patient with post-mortem autopsy results 10 months later, confirming that PiB allows accurate assessment of the amount of beta-amyloid plaques in brains of people afflicted with Alzheimer’s. A further study of the autopsied brains of 27 other patients with confirmed Alzheimer’s confirmed that PiB binds almost exclusively to beta-amyloid.

Ikonomovic, M.D. et al. 2008. Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer's disease. Brain Advance Access, published on March 12, 2008.
Full text at http://brain.oxfordjournals.org/cgi/content/abstract/awn016v1

http://www.eurekalert.org/pub_releases/2008-03/uops-svp032608.php

Brain scans show early Alzheimer's disease in people with memory problems

PET scans performed on the brains of 13 elderly men and women with mild cognitive impairment (MCI) and 14 elderly people without memory problems found that those with MCI had as much as 39% more PIB uptake in some parts of the brain than people without MCI, and about half of the MCI patients had PIB uptake in the Alzheimer's disease range. MCI subjects with at least one APOE 4 allele tended to have higher PIB uptake than MCI subjects without APOE 4. PIB is an imaging agent that allows amyloid plaque to be seen and measured.

Kemppainen, N.M. et al. 2007. PET amyloid ligand [11C]PIB uptake is increased in mild cognitive impairment. Neurology, 68, 1603-1606.

http://www.eurekalert.org/pub_releases/2007-05/aaon-bs050107.php

Compound shows promise for early detection of Alzheimer's disease

A new molecular marker called FDDNP has been found to track the progression of Alzheimer’s in PET scans more effectively than other markers, giving hope of earlier, more accurate diagnosis of the disease.

Small, G.W. et al. 2006. PET of Brain Amyloid and Tau in Mild Cognitive Impairment. The New England Journal of Medicine, 355 (25), 2652-63.

http://www.eurekalert.org/pub_releases/2006-12/nioa-nic121906.php
http://www.eurekalert.org/pub_releases/2006-12/uoc--nit121506.php

Non-invasive MRI technique distinguishes between Alzheimer's and frontotemporal dementia

A new study has found that a non-invasive imaging technique called arterial spin labeling is just as accurate and much faster and cheaper compared to invasive scanning techniques in distinguishing Alzheimer's disease from frontotemporal dementia (FTD). Frontotemporal dementia is the second-most common dementia after Alzheimer's disease. The present study aimed simply at differentiating the two types of dementia; further research needs to be done to confirm that the technique can be used to diagnose an individual patient.

The results were presented at the first International Conference on Prevention of Dementia, held June 18-21 in Washington, D.C.

http://www.eurekalert.org/pub_releases/2005-06/uoc--nmt061605.php

New computer program may enable early prediction of Alzheimer's risk

Researchers have developed a brain scan-based computer program that quickly and accurately measures metabolic activity in the hippocampus, a key brain region that shrinks with the development of Alzheimer’s. The study followed 53 normal subjects aged 54 to 80 for at least 9 years and in some cases for as long as 24 years, and found that hippocampal glucose metabolism was significantly reduced on the first scan of those 25 individuals who would later experience cognitive decline related to either mild cognitive impairment or to Alzheimer's. The findings bring hope of being able to predict who will develop Alzheimer’s at least 9 years ahead of symptoms.

Mosconi, L., Tsui, W-H., De Santi, S., Li, J., Rusinek, H., Convit, A., Li, Y., Boppana, M. & de Leon, M.J. 2005. Reduced hippocampal metabolism in MCI and AD: Automated FDG-PET image analysis. Neurology, 64, 1860-1867.

http://www.eurekalert.org/pub_releases/2005-06/nyum-ncp061505.php

Expert system gives non-experts diagnostic accuracy of Alzheimer's disease from PET scans

A computer program has been developed that enhances the diagnostic accuracy of PET scans with Alzheimer's patients. A PET scan is a very reliable noninvasive test, but only in the hands of an experienced investigator. The new program enables even inexperienced doctors to diagnose reliably, hopefully enabling diagnosis to occur earlier.

Siessmeier, T., Oehm, S., Drzezga, A., Fellgiebel, A., Schreckenberger, M., Uthman, T. & Bartenstein, P. 2005. Use of an Expert System for the Diagnosis of Suspected Alzheimer's Disease (AD) With FDG PET. Presented at the Society of Nuclear Medicine's 52nd Annual Meeting in Toronto; Scientific Poster Abstract 155

http://www.eurekalert.org/pub_releases/2005-06/sonm-esd061605.php

Pet scans detect brain differences in people at risk for Alzheimer's

Brain imaging of 32 participants, mostly in their 60s and 70s, has found clear differences in brain function between healthy people who carry a genetic risk factor for Alzheimer's disease and those who lack the factor. More research is needed before it's known for certain if the difference is an early sign of Alzheimer's.

Scarmeas, N., Habeck, C., Anderson, K.E., Hilton, J., Devanand, D.P., Pelton, G.H., Tabert, M.H., Flynn, J., Park, A., Ciappa, A., Tycko, B. & Stern, Y. 2004. Altered PET Functional Brain Responses in Cognitively Intact Elderly Persons at Risk for Alzheimer Disease (Carriers of the {epsilon}4 Allele). American Journal of Geriatric Psychiatry, 12, 596-605.

http://www.eurekalert.org/pub_releases/2004-11/cuco-psd111904.php

Rate of brain volume loss predicts dementia

A new study has found that rates of total brain volume loss may help identify patients with mild cognitive impairment who are at high risk of developing dementia. The study followed 55 people over 14 years, and found that loss of volume in the hippocampus predicted which mildly cognitively impaired individuals would stay stable and which would decline to Alzheimer's with 70% accuracy, while the rate of total brain volume loss was 62% accurate in predicting cognitive outcome. Combining both variables produced the strongest model: 75% accuracy. The discovery could help doctors plan early treatment strategies and prevention studies.

The study was presented at the 56th annual meeting of the American Academy of Neurology in San Francisco.

http://www.eurekalert.org/pub_releases/2004-04/ohs-osr042804.php

New PET technique improves accuracy of early diagnosis of Alzheimer's

A new study identifies a new Positron Emission Tomography (PET) scanning technique that may increase the already high accuracy of PET in diagnosing Alzheimer’s at a very early stage. Altered brain connections between the entorhinal cortex and both hemispheres of the brain can be clearly identified with 18F-FDG PET. The entorhinal cortex is a critical site for learning and memory. It now appears that most of its connections to the neocortex in both hemispheres are destroyed at a very early stage of Alzheimer’s.

Mosconi, L., Pupi, A., De Cristofaro, M.T.R., Fayyaz, M. & Herholz, K. 2004. Functional Interactions of the Entorhinal Cortex: An 18F-FDG PET Study on Normal Aging and Alzheimer's Disease. Journal of Nuclear Medicine, 45 (3), 382-392.

http://www.eurekalert.org/pub_releases/2004-03/sonm-nss031104.php

New technique allows sight of amyloid plaque in living brains

The first human study has now been completed of a compound that, through PET scanning, enables researchers to see the amyloid plaque deposits in the brains of Alzheimer’s sufferers. The compound has been dubbed Pittsburgh Compound B (PIB), and should be a very useful new tool in Alzheimer’s research.

Klunk, W.E. et al. 2004. Imaging brain amyloid in Alzheimer's disease with Pittsburgh Compound-B. Annals of Neurology, 55 (3), 306-319.

http://www.eurekalert.org/pub_releases/2004-01/uopm-uop012104.php

Hippocampal damage seen in those with alcoholic memory disorder and those with Alzheimer's

A comparison between the brains of five men with alcoholic Korsakoff's syndrome and the brains of men with Alzheimer's disease as well as the brains of healthy men, found that the brains of all Korsakoff's patients and Alzheimer's patients were comparable in significant volume loss in the hippocampus. Greater hippocampal damage (for Korsakoff's patients) and smaller hippocampal size (for Alzheimer’s) was correlated with poorer memory performance. It is suggested that, although there are of course a number of differences between these disorders, the nature of the memory impairment may be the same. Awareness of the similarities may help detection of both disorders.

Sullivan, E.V. & Marsh, L. 2003. Hippocampal volume deficits in alcoholic Korsakoff’s syndrome. Neurology, 61, 1716-1719.

http://www.eurekalert.org/pub_releases/2003-12/aaon-seu121503.php

Imaging techniques help distinguish between Alzheimer's and vascular dementia

A combination of magnetic resonance imaging (MRI) and MR spectroscopy has enabled researchers to differentiate between Alzheimer’s and dementia caused by poor blood flow (vascular dementia). Comparison of the brains of those with Alzheimer’s, those who had suffered subcortical ischemic vascular dementia (SIVD), and those belonging to cognitively normal older adults, also found significant differences in the chemical signature of various brain regions, leading researchers to suggest that in patients with SIVD, there may only be neuronal dysfunction rather than neuronal loss, offering hope for recovery of neuronal function in these areas. More research is needed to confirm these results.

Schuff, N. et al. 2003. Different patterns of N-acetylaspartate loss in subcortical ischemic vascular dementia and AD. Neurology, 61, 358-364.

Activity in the mediotemporal lobe lower in elderly with poor memory

An imaging study has revealed that, although there is no difference on standard MRI scans,scans showing the amount of oxygen (and thus activity) find that elderly persons with a poor memory have less activity in the mediotemporal lobe when storing new information than elderly persons with a normally functioning memory.This more sensitive scan may help early diagnosis of Alzheimer's.

The research was done as part of a doctoral thesis by Dr Sander Daselaar.

http://www.eurekalert.org/pub_releases/2003-03/nofs-svp032103.php

PET scans can help early diagnosis of Alzheimer's

Early diagnosis of Alzheimer’s is becoming more and more important, with the arrival of drugs and therapies which can help slow the progression of the disease, if caught early. A new study reveals that PET scans may be able to identify Alzheimer’s, and distinguish it from other dementias.

Initial results were presented recently at the International Conference on Alzheimer's Disease and Related Disorders.

http://www.eurekalert.org/pub_releases/2002-11/uomh-sit110102.php

Value of PET scans in diagnosing Alzheimer’s

A new study has measured the advantage of early diagnosis of Alzheimer’s using PET scanning. The study compared the use of two strategies for diagnosing Alzheimer's: clinical evaluation using the American Academy of Neurology (AAN) 2001 recommendations, and the same with the addition of a PET scan. They concluded that, although both approaches accurately diagnosed most Alzheimer's patients, the appropriate use of PET reduced erroneous diagnoses by half. A review of the literature suggested conventional methods would falsely attribute symptoms to early Alzheimer's in 23 cases out of 100, and overlook eight cases. Analysis suggested that incorporating PET scans would have prevented 11 of the 23 false positives and five of the eight false negatives. The researchers estimated that PET could cut unnecessary drug therapy by half (48%) and reduce months in a nursing home by 62%.

Cummings, J.L. 2002. 2-Deoxy-2-[18F]Fluoro-D-Glucose Positron Emission Tomography in Alzheimer's Diagnosis: Time for Technology Transfer, Molecular Imaging and Biology, 4 (6), 385-386.

http://www.eurekalert.org/pub_releases/2002-10/uoc--uss100402.php

MRI brain scan may detect Alzheimer's disease decades before first symptoms

MRI scans of the brain may detect Alzheimer’s disease decades before the first clinical signs of dementia occur, according to a study revealing that shrinkage of the hippocampus occurs very early in the disease process.

Gosche, K.M., Mortimer, J.A., Smith, C.D., Markesbery, W.R. & Snowdon, D.A. 2002. Hippocampal volume as an index of Alzheimer neuropathology: Findings from the Nun Study. Neurology, 58, 1476-1482.

http://www.eurekalert.org/pub_releases/2002-05/uosf-mbs052302.php

Brain scans predict cognitive impairment

A three-year study of 48 healthy people from 60 to 80 years old, by New York University School of Medicine researchers, predicted which healthy elderly men and women would develop memory impairment based on scans of their brains. At the beginning of the study, everyone scored within the normal range on a battery of tests typically used to detect early loss of memory and other mental skills. However, PET scans revealed a reduction in glucose metabolism in an area of the brain called the entorhinal cortex among 12 people. Three years later, 11 of these people had experienced mild cognitive impairment and one had developed Alzheimer's disease. "Our work extends the use of PET scanning to identifying in normal aging subjects the earliest metabolic abnormalities that may lead to the memory losses referred to as mild cognitive impairment (MCI). The diagnosis of MCI carries a high risk for future Alzheimer's disease."

Leon, M. J. de, Convit, A., Wolf, O. T., Tarshish, C. Y., DeSanti, S., Rusinek, H., … Fowler, J. (2001). Prediction of cognitive decline in normal elderly subjects with 2-[18F]fluoro-2-deoxy-d-glucose/positron-emission tomography (FDG/PET). Proceedings of the National Academy of Sciences, 98(19), 10966–10971. doi:10.1073/pnas.191044198

http://www.eurekalert.org/pub_releases/2001-09/nyum-bps090701.php

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Alzheimer's: Causes

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

Role of fatty acids in Alzheimer's disease

Fatty acids are rapidly taken up by the brain and incorporated into phospholipids, a class of fats that form the membrane or barrier that shields the content of cells from the external environment. Now genetically engineered mice have revealed that there is a striking increase in arachidonic acid and related metabolites in the hippocampus. Removal or reduction of the enzyme that releases this acid prevented memory deficits in the Alzheimer mice. It’s thought that the acid causes too much excitation.

Sanchez-Mejia, R.O. et al. 2008. Phospholipase A2 reduction ameliorates cognitive deficits in a mouse model of Alzheimer's disease. Nature Neuroscience, 11, 1311-1318.

http://www.eurekalert.org/pub_releases/2008-10/gi-gsi101408.php

Support for view of Alzheimer's as form of diabetes

Research in the last few years has raised the possibility that Alzheimer’s memory loss could be due to a third form of diabetes. A new study clarifies the connection between insulin and Alzheimer’s. It seems that the toxic protein ADDL, found in the brains of individuals with Alzheimer’s, removes insulin receptors from nerve cells, rendering those neurons insulin resistant. The findings suggest that some existing drugs now used to treat diabetic patients may be useful for Alzheimer’s treatment.

Zhao,W-Q. et al. 2007. Amyloid beta oligomers induce impairment of neuronal insulin receptors. FASEB Journal, published online ahead of print August 24.

http://www.eurekalert.org/pub_releases/2007-09/nu-dst092607.php

Link between size of hippocampus and progression to Alzheimer's

A study of 20 older adults with mild cognitive impairment has found that the hippocampus was smaller in those who developed into Alzheimer's during the 3 year period.

Apostolova, L.G. et al. 2006. Conversion of Mild Cognitive Impairment to Alzheimer Disease Predicted by Hippocampal Atrophy Maps. Archives of Neurology, 63, 693-699.

http://www.eurekalert.org/pub_releases/2006-05/uoc--rml050406.php

Post-mortem brain studies reveal features of mild cognitive impairment

Autopsies have revealed that the brains of patients with mild cognitive impairment display pathologic features that appear to place them at an intermediate stage between normal aging and Alzheimer's disease. For instance, the patients had begun developing neurofibrillary tangles, but the number of plaques was similar to that in healthy patients. All patients with mild cognitive impairment had abnormalities in their temporal lobes, which likely caused their cognitive difficulties, and many also had abnormalities in other areas that did not relate to the features of Alzheimer's disease. In a second study, of 34 patients with mild cognitive impairment who had progressed to clinical dementia before their deaths, 24 were diagnosed (post-mortem) with Alzheimer’s, and 10 with other types of dementia. As in the other study, all patients had abnormalities in their temporal lobes.

Petersen, R.C. et al. 2006. Neuropathologic Features of Amnestic Mild Cognitive Impairment. Archives of Neurology, 63, 665-672.

Jicha, G.A. et al. 2006. Neuropathologic Outcome of Mild Cognitive Impairment Following Progression to Clinical Dementia. Archives of Neurology, 63, 674-681.

http://www.eurekalert.org/pub_releases/2006-05/jaaj-pbs050406.php

Neurons can produce apolipoprotein E

Apolipoprotein E has been known to be synthesized in the brain in support cells such as astrocytes, microglia, and ependymal layer cells. Controversial for the last decade has been the question of whether or not neurons can produce apoE. Using a unique mouse model, researchers have now demonstrated that neurons can produce apoE, but only in response to injury to the brain.

Xu, Q. et al. 2006. Profile and Regulation of Apolipoprotein E (ApoE) Expression in the CNS in Mice with Targeting of Green Fluorescent Protein Gene to the ApoE Locus. Journal of Neuroscience, 26, 4985-4994.

http://www.eurekalert.org/pub_releases/2006-05/gi-gsp051006.php

Protein identified as cause of memory loss

Researchers have identified a substance in the brain that is proven to cause memory loss, giving drug developers a target for creating drugs to treat memory loss in people with dementia. The substance is a form of the amyloid-beta protein that is distinct from plaques and has been given the name Ab*56. Ab*56 impairs memory independently of plaques or neuronal loss, and may contribute to cognitive deficits associated with Alzheimer's disease.

Lesné, S. et al. 2006. A specific amyloid-beta protein assembly in the brain impairs memory. Nature, 440, 352-357.

http://www.eurekalert.org/pub_releases/2006-03/uom-uom_1031306.php

Reduced insulin in the brain triggers Alzheimer's degeneration

By depleting insulin and its related proteins in the brain, researchers have replicated the progression of Alzheimer's disease – including plaque deposits, neurofibrillary tangles, impaired cognitive functioning, cell loss and overall brain deterioration – in an experimental animal model. Brain deterioration was not related to the pancreas, raising the possibility that Alzheimer's is a neuroendocrine disorder, or a Type 3 diabetes.

Lester-Coll, N. et al. 2006. Intracerebral streptozotocin model of type 3 diabetes: relevance to sporadic Alzheimer’s disease. Journal of Alzheimer’s Disease, 9(1)

http://www.eurekalert.org/pub_releases/2006-03/l-rii031606.php

Pin1 enzyme key in preventing onset of Alzheimer's disease

An enzyme called Pin1, previously shown to prevent the formation of the tangles characteristic of Alzheimer's brains, has now been shown to also play a pivotal role in guarding against the development of the plaques that are also characteristic of Alzheimer's. These findings establish a direct link between amyloid plaques and tau tangles, and provide further evidence that Pin1 (prolyl isomerase) is essential to protect individuals from age-related neurodegeneration.

Pastorino, L. et al. 2006. The prolyl isomerase Pin1 regulates amyloid precursor protein processing and amyloid-beta production Nature, 440, 528-534.

http://www.eurekalert.org/pub_releases/2006-03/hms-nrs032006.php

Link between APOE and memory neurotransmitter

A new link in the complex chain of Alzheimer’s development has been found. It’s been found that receptors that bind apolipoprotein E (APOE) and those that bind glutamate are in fact connected, separated only by a small protein. It may be that inefficient or high levels of APOE are clogging these binding sites, preventing glutamate from activating the processes necessary to form memories. It may also be that the APOE4 variant — associated with Alzheimer's — is less efficient at removing lipid debris in the brain than is APOE2 or APOE3.

Hoe, H-S. et al. 2006. Apolipoprotein E Receptor 2 Interactions with the N-Methyl-D-aspartate Receptor. Journal of Biological Chemistry, 281, 3425-3431.

http://www.eurekalert.org/pub_releases/2006-02/gumc-nrr020906.php

Two pathways lead to Alzheimer's disease

Mild cognitive impairment (MCI), a transitional stage between normal cognition and Alzheimer's disease, has been categorized into two sub-types on the basis of differing symptoms. Those with the amnesic subtype (MCI-A) have memory impairments only, while those with the multiple cognitive domain subtype (MCI-MCD) have other types of mild impairments, such as in judgment or language, and mild or no memory loss. Both sub-types progress to Alzheimer's disease at the same rate. A new imaging technique has now revealed that these types do in fact have different pathologies. The hippocampus of patients with MCI-A was not significantly different from that of Alzheimer's patients (who show substantial shrinkage), but the hippocampus of those with MCI-MCD was not significantly different from that of the healthy controls.

Becker, J.T., Davis, S.W., Hayashi, K.M., Meltzer, C.C., Toga, A.W., Lopez, O.L., Thompson, P.M., for the Imaging Methods and Analysis in Geriatrics Research Group. 2006. Three-dimensional Patterns of Hippocampal Atrophy in Mild Cognitive Impairment. Archives of Neurology, 63, 97-101.

http://www.eurekalert.org/pub_releases/2006-01/uopm-tpf010606.php

Key genetic risk for Alzheimer's linked to myelin breakdown

Myelin, the fatty insulation coating the brain's internal wiring, builds up in childhood, and breaks down as we age. Myelin is critical for speedy communication between neurons. A new study supports a growing body of evidence that myelin breakdown is a key contributor to the onset of Alzheimer disease later in life. Moreover, it has also revealed that the severity and rate of myelin breakdown in healthy older individuals is associated with ApoE status. Thus both age, the most important risk factor for Alzheimer disease, and ApoE status, the second-most important risk factor, seem to act through the process of myelin breakdown.

Bartzokis, G., Lu, P.H., Geschwind, D.H., Edwards, N., Mintz, J. & Cummings, J.L. 2006. Apolipoprotein E Genotype and Age-Related Myelin Breakdown in Healthy Individuals: Implications for Cognitive Decline and Dementia. Archives of General Psychiatry, 63, 63-72.

http://www.eurekalert.org/pub_releases/2006-01/uoc--isl122805.php

Study links Alzheimer's and Down’s syndrome

New research suggests the cognitive problems observed in Alzheimer’s are related to defects in the machinery controlling neuronal connections — PAK enzyme signaling pathways. PAK (p21-activated kinase) enzymes form a family that includes two members (PAK1 and PAK3) that play critical roles in learning and memory. Humans with genetic loss of PAK3 have severe mental retardation. The study reveals that both PAK1 and PAK3 are abnormally distributed and reduced in Alzheimer patients, and that beta-amyloid was directly involved in PAK signaling deficits. The finding suggests therapies designed to address the PAK defect could treat cognitive problems in both patient populations.

Zhao, L. et al. 2006. Role of p21-activated kinase pathway defects in the cognitive deficits of Alzheimer disease. Nature Neuroscience, 9, 234–242.

http://www.eurekalert.org/pub_releases/2006-01/uoc--sid012506.php

New technique finds higher levels of creatine in Alzheimer’s brains

Creatine is involved in the maintaining the energy balance in the brain, but creatine, being small and very soluble, is difficult to detect. A new study has now succeeded in detecting creatine in situ, in brain tissue, and has found relatively large deposits in the hippocampus of Alzheimer’s brains. The finding suggests an overlooked aspect of energy disturbance in Alzheimer's disease, but further research is needed to understand it.
Gallant, M. et al. 2006. Focally Elevated Creatine Detected in Amyloid Precursor Protein (APP) Transgenic Mice and Alzheimer Disease Brain Tissue. Journal of Biological Chemistry, 281, 5-8.
http://www.eurekalert.org/pub_releases/2005-12/uow-iar122105.php

More light on apoE4 and Alzheimer’s

A mutant form of a protein that transports cholesterol, apolipoprotein E (apoE) has long been recognized as a causative factor for Alzheimer's disease, but exactly how has been unclear. 299 amino acids are associated with apoE4, but new research has now found which of these amino acids are toxic. These toxic fragments all reside in the mitochondria (the “energy powerhouse” of the cell). The finding suggests a new therapeutic approach, involving blocking interaction of apoE4 fragments with the mitochondria.

Ye, S. et al. 2005. Apolipoprotein (apo) E4 enhances amyloid peptide production in cultured neuronal cells: ApoE structure as a potential therapeutic target. Proceedings of the National Academy of Science, 102 (51), 18700-18705.

http://www.eurekalert.org/pub_releases/2005-12/gi-gsl121405.php

p25 only good in small doses

Elevated levels of a key brain regulatory enzyme called Cdk5 and an associated regulatory protein called p25 have been found in the brains of Alzheimer’s patients. A new mouse study has found that switching on p25 in the hippocampus for only two weeks actually enhanced learning and memory compared to normal mice; however mice in which p25 had been switched on for six weeks showed impaired learning and memory. These mice also showed significant brain atrophy and loss of hippocampal neurons. The two-week pulse of p25 did not cause neurodegeneration and had long-lasting effects on enhancing memory. The researchers suggest that p25 might be produced to compensate for the loss of Cdk5 activity during aging, however chronically high levels lead to neuronal cell death. The findings are consistent with several recent studies suggesting that in the development of Alzheimer’s, compensatory mechanisms that initially enhance neuroplasticity eventually become maladaptive when chronically activated.

Fischer, A., Sananbenesi, F., Pang, P.T., Lu, B. & Tsai, L-H. 2005. Opposing roles of transient and prolonged expression of p25 in synaptic plasticity and hippocampus-dependent memory. Neuron, 48, 825–838.

http://www.eurekalert.org/pub_releases/2005-12/cp-aje120505.php

“Default” brain activity implicated in Alzheimer's disease

Here’s an unexpected finding: imaging of the brains of 764 adults of various ages has revealed that the regions that are active when people are in “default mode” — not concentrating on anything in particular, just musing to yourself — are the same regions that develop plaques in Alzheimer’s. They also found that, when asked to concentrate on a specific task, individuals with Alzheimer’s showed increased activity in these posterior cortical regions, rather than the decreased activity seen in young, healthy adults. The researchers speculate that dementia may in fact be a consequence of normal cognitive function — a possibility that hasn’t heretofore been considered. The findings raise the hope of developing methods to detect precursors of the disease long before it develops.

Buckner, R.L. et al. 2005. Molecular, Structural, and Functional Characterization of Alzheimer's Disease: Evidence for a Relationship between Default Activity, Amyloid, and Memory. Journal of Neuroscience, 25, 7709-7717.

http://www.eurekalert.org/pub_releases/2005-08/hhmi-bai082405.php

How Alzheimer's impacts important brain cell function

Researchers have found that synaptic proteins, proteins involved in brain cell communications, decrease in the brains of Alzheimer's patients compared to healthy brains from people in the same age range. The decrease in the frontal cortex was more severe than in other portions of the brain. They also found synaptic protein levels were even lower in the brains of patients in the early stages of Alzheimer's disease, suggesting that the loss of these proteins happens very early in the disease process. The reduction of synaptic proteins may be caused by mitochondrial dysfunction, a well-documented occurrence in Alzheimer's.

Reddy, P.H., Mani, G., Park, B.S., Jacques, J., Murdoch, G., Whetsell, W.Jr., Kaye, J. & Manczak, M. 2005. Differential loss of synaptic proteins in Alzheimer’s disease: Implications for synaptic dysfunction Journal of Alzheimer's Disease, 7(2),103-117.

http://www.eurekalert.org/pub_releases/2005-04/ohs-ord040605.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

Why diet, hormones, exercise might delay Alzheimer’s

A theory that changes in fat metabolism in the membranes of nerve cells play a role in Alzheimer's has been supported in a recent study. The study found significantly higher levels of ceramide and cholesterol in the middle frontal gyrus of Alzheimer's patients. The researchers suggest that alterations in fats (especially cholesterol and ceramide) may contribute to a "neurodegenerative cascade" that destroys neurons in Alzheimer's, and that the accumulation of ceramide and cholesterol is triggered by the oxidative stress brought on by the presence of the toxic beta amyloid peptide. The study also suggests a reason for why antioxidants such as vitamin E might delay the onset of Alzheimer's: treatment with Vitamin E reduced the levels of ceramide and cholesterol, resulting in a significant decrease in the number of neurons killed by the beta amyloid and oxidative stress.

Cutler, R.G., Kelly, J., Storie, K., Pedersen, W.A., Tammara, A., Hatanpaa, K., Troncoso, J.C. & Mattson, M.P. 2004. Involvement of oxidative stress-induced abnormalities in ceramide and cholesterol metabolism in brain aging and Alzheimer's disease. PNAS, 101, 2070-5.

http://www.eurekalert.org/pub_releases/2004-02/aaft-nsm021004.php

Late-life Alzheimer's begins in midlife

A new model of human brain aging identifies midlife breakdown of myelin, a fatty insulation with very high cholesterol content that wraps tightly around axons (part of the neurons) and enables messages to pass along the “wiring” of the brain speedily, as a possible key to the onset of Alzheimer's disease later in life. Imaging studies and examination of brain tissue shows that the brain's wiring develops until middle age and then begins to decline as the breakdown of myelin triggers a destructive domino affect. It is suggested that genetic factors coupled with the brain's own developmental process of increasing cholesterol and iron levels in middle age help degrade the myelin. The complex connections that take the longest to develop and allow humans to think at their highest level are among the first to deteriorate as the brain's myelin breaks down in reverse order of development. The model suggests that the best time to address the inevitability of myelin breakdown is when it begins, in middle age. Possible preventive therapies include cholesterol- and iron-lowering medications, anti-inflammatory medications, diet and exercise programs and possibly hormone replacement therapy designed to prevent menopause rather than simply ease the symptoms. Education and cognitively stimulating activities may also stimulate the production of myelin.

Bartzokis, G. 2003. Age-related myelin breakdown: a developmental model of cognitive decline and Alzheimer's disease. Neurobiology of Aging, 25(1), 5-18.

http://www.eurekalert.org/pub_releases/2003-12/uoc--mbc122303.php

A nicotine by-product implicated in Alzheimer’s

A previously unrecognized chemical process has been discovered, by which a chemical called nornicotine, naturally present in tobacco and produced as a metabolite of nicotine, permanently and irreversibly modifies proteins in the body. These modified proteins interact with other chemicals in the body to form a variety of compounds known as advanced glycation endproducts. Advanced glycation endproducts have previously been implicated in numerous diseases including diabetes, cancer, atherosclerosis, and Alzheimer’s disease.

Dickerson, T.J. & Janda, K.D. 2002. A previously undescribed chemical link between smoking and metabolic disease. Proc. Natl. Acad. Sci. USA, 99 (23), 15084-15088.

http://www.eurekalert.org/pub_releases/2002-10/sri-aka102402.php

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