News reports of research into Alzheimer's disease July - December 2005

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There's a glossary of terms used in Alzheimer's research.

Disclaimer:
This section began as an offshoot of my gathering of news items about memory. I am not a medical expert. My background is in psychology. The information I have gathered here should not be taken as providing any advice.

December

Brain activity, drugs could affect Alzheimer's progression

Mouse studies have revealed that the activity of connections among brain cells significantly affects levels of the toxic protein beta-amyloid, suggesting that the kind of mental activity people practice or drugs they might take for depression or anxiety could affect their risk of Alzheimer’s or the disease progression. The researchers suggest that enriched environments may increase overall synaptic activity in some brain regions and decrease it in others. Increased activity in some brain regions might result in increased susceptibility to beta-amyloid deposition if the activated neural circuits contain high levels of human APP expression. Drugs used to treat neuropsychiatric disorders directly influence neurotransmitters, and their receptors, thereby altering synaptic activity.
The article appeared in the December 22 issue of Neuron. Full reference
http://www.eurekalert.org/pub_releases/2005-12/cp-bad121505.htm

Testosterone improves quality of life

A 24-week study involving 16 male patients diagnosed with mild Alzheimer disease and 22 healthy male controls found that Alzheimer’s patients who received daily testosterone treatment showed significant improvement on a quality-of-life instrument that encompasses memory, interpersonal relationships, physical health, energy, living situation and overall well-being, however improvement in memory or other cognitive skills using cognitive tests did not reach significance. Among healthy controls, those receiving testosterone showed a non-significant trend toward greater improvement in self-rated quality of life.
The study was published December 12 in an early online release of Archives of Neurology. Full reference
Full text at http://archneur.ama-assn.org/cgi/content/full/63.2.nct50002v1
http://www.eurekalert.org/pub_releases/2005-12/uoc--apt120805.htm

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

A compound isolated from a cyanobacterium, a type of blue-green algae (‘pond scum’) shows promise of becoming a natural drug candidate for fighting Alzheimer's. Nostocarboline (the newly isolated compound) is a potent inhibitor of cholinesterase, with a potency comparable to galanthamine.
The study was published in the December 26 issue of the Journal of Natural Product. Full reference
http://www.eurekalert.org/pub_releases/2005-12/acs-ncf122705.htm

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.
The finding was reported in the November issue of the Journal of Biological Chemistry. Full reference
http://www.eurekalert.org/pub_releases/2005-12/uow-iar122105.htm

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.
The findings were published in the December 20 issue of the Proceedings of the National Academy of Science. Full reference
http://www.eurekalert.org/pub_releases/2005-12/gi-gsl121405.htm

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.
The report appeared in the December 8 issue of Neuron. Full reference
http://www.eurekalert.org/pub_releases/2005-12/cp-aje120505.htm

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November

Alzheimer's disease onset tied to lapses in attention

A new finding may lead to another tool to detect Alzheimer’s early, and also offers support for the idea that breakdowns in attention may be at the heart of many of the memory problems experienced by Alzheimer’s sufferers. The study, involving 94 older adults (average age mid-70s) who were either healthy controls or in the early stages of Alzheimer’s, found those in the early stages of Alzheimer's disease had greater difficulty shifting attention back and forth between competing sources of information in a dichotic listening task. The finding may also explain why early-stage patients start to struggle with everyday tasks that call for processing a lot of information, such as driving. Prior research has found that performance on dichotic listening predicts accident rates in commercial bus drivers.
[note: this study was briefly reported on in September, but only mentioning its use as an early test]
The study was published in the September issue of Neuropsychology. Full reference
Full text is available at: www.apa.org/journals/releases/neu195687.pdf
http://www.eurekalert.org/pub_releases/2005-11/wuis-ado110905.htm

Cholesterol treatment, including statins, may slow Alzheimer's disease progression

A study following 342 Alzheimer’s patients attending a memory clinic for almost three years has found that the disease progressed significantly more slowly in patients given cholesterol lowering drugs. A larger trial will be needed to confirm the findings.
The study appeared in the December issue of the Journal of Neurology Neurosurgery and Psychiatry. Full reference
http://www.eurekalert.org/pub_releases/2005-11/bsj-cti111605.htm

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

In cell studies, resveratrol has been found to lower levels of amyloid-beta peptides. Resveratrol is a natural compound occurring in abundance in grapes, berries and peanuts. The highest concentration has been reported in wines prepared from Pinot Noir grapes. The anti-amyloidogenic effect of resveratrol observed in cell cultures does not however necessarily mean that the beneficial effect can result simply from eating grapes or drinking wine. Further research aims to develop more active and more stable compounds.
The study was published in the November 11 issue of the Journal of Biological Chemistry. Full reference
http://www.eurekalert.org/pub_releases/2005-11/asfb-ciw110305.htm
http://www.sciam.com/article.cfm?chanID=sa003&articleID=000581B2-EE9B-136B-AE9B83414B7F0000

Progression of Alzheimer's disease revealed

A new imaging agent is giving researchers information never before available about how and where Alzheimer’s progresses in the brain. Results suggest that amyloid plaques deposit sequentially, first appearing in the cingulate cortex/precuneus and frontal cortex areas, then progressing to the parietal and temporal cortex and caudate, and finally reaching the occipital cortex and sensory-motor cortex. These findings may explain why memory and judgment are often the brain functions first affected in Alzheimer's disease.
The findings were presented at the 35th Annual Meeting of the Society for Neuroscience, being held Nov. 12-16 in Washington, D.C. Reference
http://www.eurekalert.org/pub_releases/2005-11/uopm-ctt111105.htm

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October

A new analysis of a standard brain test may help predict dementia

A new study gives promise of early diagnosis of Alzheimer’s. A computer analysis of an EEG (electroencephalograph) test was almost 95% accurate in predicting those people in their 60s and 70s who would develop dementia over the next 7 to 10 years. There were several distinctive features in the brain waves of those who would later show cognitive impairment. The study now needs to be replicated with a larger sample.
The study was published online on 6 October in Neurobiology of Aging. Full reference
http://www.eurekalert.org/pub_releases/2005-10/dumc-ana100505.htm

Gas-blockers might slow down Alzheimer's disease

Beta-amyloid is known to cause brain cells to make an inhibitor of an enzyme that triggers the production of nitric oxide (iNOS). This enzyme is normally turned on during infection and is needed to help immune cells destroy invading pathogens, but it is not normally found in the brain, where it may cause cellular damage that destroys neurons. Although it’s long been known that iNOS is present in the brain lesions of Alzheimer’s patients, it hasn’t been known whether its presence makes things worse. A new study has now shown that Alzheimer's-prone mice that lack iNOS live twice as long and develop fewer brain lesions than iNOS-expressing mice. The researchers suggest that iNOS inhibitors might turn out to be an effective in slowing the progression of Alzheimer's disease.
The study appeared in the November 7 issue of the Journal of Experimental Medicine. Full reference
http://www.eurekalert.org/pub_releases/2005-10/joem-gms102005.htm

New light on how amyloid beta accumulation leads to long-term memory loss

A study using genetically engineered mice has shed new light on why the damage to brain tissue seen in Alzheimer’s leads to the loss of long-term memories. It seems that the accumulation of amyloid-beta peptides can deplete key proteins in the hippocampus, and this process can be worsened by increased activity of an enzyme called Fyn. The conversion of new information into long-term memories requires proteins (such as Arc and Fos) that help strengthen the synapses between specialized neurons in the hippocampus. Fyn is located at the synapses, where it regulates the activity of several memory-related proteins; increases in Fyn activity significantly increase the susceptibility of the hippocampal granule cells to the amyloid beta-induced depletion of memory proteins.
The research was reported in two companion papers in the October 19 issue of the Journal of Neuroscience. Full reference 2
http://www.eurekalert.org/pub_releases/2005-10/gi-szi101705.htm

Concussions increase chance of age-related cognitive impairment

A study involving retired National Football League players found that they had a 37% higher risk of Alzheimer's than other U.S. males of the same age. Some 60.8% of the retired players reported having sustained at least one concussion during their professional playing career, and 24% reported sustaining three or more concussions. Those with three or more concussions had a five-fold greater chance of having been diagnosed with mild cognitive impairment and a three-fold prevalence of reported significant memory problems compared to those players without a history of concussion. As the study was based on self-reported answers to the health questions, further studies are needed to confirm the findings, but it does seem likely that head injuries earlier in life increase the chance of developing dementia or mild cognitive impairment.
The study appeared in the October issue of Neurosurgery. Full reference
http://www.eurekalert.org/pub_releases/2005-10/uonc-nsa101005.htm

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September

More sensitive tests for predicting Alzheimer's

The first study used data from 119 participants in the Longitudinal Aging Study Amsterdam. The memory test scores of those who two years later developed Alzheimer's were compared with the scores of those who stayed healthy. Three tests were very good at predicting who would later develop Alzheimer's: a Paired-Associate Learning Test, which cued participants to recall five semantically related and five semantically unrelated pairs of words; a Perceptual Identification Task, which measured how fast participants read aloud words briefly presented on a computer screen; a Visual Association Test, which cued participants to recall six line drawings of common objects that had been presented earlier in an illogical interaction with another object or cue. On the word-pair memory test, people destined to develop Alzheimer's disease didn't do any better when words were related than when they weren't, suggesting they’d already lost deep semantic knowledge. On the word-reading test, word repetition didn't help high-risk participants to perform better, a sign that implicit learning was impaired. The popular Mini Mental Status Exam (MMSE), a test mainly sensitive to episodic memory, was not as good a predictor.
In the second study, a dichotic listening task, which measures how well people process information when they hear one thing in the left ear and another in the right ear, was found to also be predictive of Alzheimer’s, confirming that people have problems with selective attention very early in the disease.
The studies appear in the September issue of Neuropsychology. Full reference 2
Full text of the both articles is available at www.apa.org/journals/releases/neu195629.pdf
and www.apa.org/journals/releases/neu195687.pdf
http://www.eurekalert.org/pub_releases/2005-09/apa-pfm092105.htm

Loss of body mass linked to development of Alzheimer's disease

People with Alzheimer's disease are known to lose weight and body mass after they have the disease, but now the Religious Orders Study has revealed that loss in body mass index is associated with a greater risk of developing the disease. People who lost approximately one unit of BMI per year had a 35% greater risk than people with no change in BMI; those with no change in BMI had a 20% greater risk of developing the disease than that of people who gained six-tenths of a unit of BMI per year. A similar relationship was also found between changes in BMI and rate of cognitive decline. The findings are supported by recently published findings of the Honolulu-Asia Aging Study, showing that dementia-associated weight loss in Japanese-American men begins before the onset of dementia and accelerates by the time of diagnosis.
The research was reported in the September 27 issue of Neurology. Full reference
http://www.eurekalert.org/pub_releases/2005-09/nioa-lob092105.htm

Green tea ingredient prevents Alzheimer's-like brain damage in mice

A major antioxidant in green tea (epigallocatechin-3-gallate (EGCG)) has prevented Alzheimer's-like damage in the brains of genetically engineered mice. EGCG decreased production of beta-amyloid. It may be that EGCG dietary supplementation could help prevent and treat the disease. However, other flavinoids in green tea actually oppose naturally-occurring EGCG's ability to prevent the harmful build-up of beta-amyloid; thus, drinking green tea alone is unlikely to have a beneficial effect through the same mechanism.
The report was published in the September 21 issue of the Journal of Neuroscience. Full reference
http://www.eurekalert.org/pub_releases/2005-09/uosf-gti091505.htm

Gene therapy reversed memory loss in mice

A study using genetically engineered mice has reversed the rodents' memory loss by silencing beta-secretase (an enzyme that helps produce amyloid plaques). The size and number of plaques were reduced by two-thirds within a month.
The report appeared in the October 1 issue of Nature Neuroscience. Full reference
http://www.eurekalert.org/pub_releases/2005-09/si-tak092005.htm

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August

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.”
The study was reported in the August 6 issue of the British Medical Journal. Full reference

New research suggests heart bypass surgery increases risk of Alzheimer's disease

Patients who have either coronary artery bypass graft surgery or coronary angioplasty are at an increased risk of developing Alzheimer's disease, according to a study involving 5,216 people who underwent coronary artery bypass graft surgery (CABG) and 3,954 people who had a percutaneous transluminal coronary angioplasty (PTCA) in 1996 and 1997. The researchers suggest the trauma to the brain during surgery is the principle cause.
The report appeared in the August issue of the Journal of Alzheimer's Disease. Full reference
http://www.eurekalert.org/pub_releases/2005-08/cwru-nrs082405.htm

Folates more effective in limiting Alzheimer's disease risk than antioxidants, other nutrients

Analysis of data from the Baltimore Longitudinal Study of Aging has revealed that those with higher intake of folates, vitamin E and vitamin B6 had a lower risk of developing Alzheimer’s. When the three vitamins were analyzed together, only folates were associated with a significantly decreased risk. Those who had at least 400mcg of folates a day (the recommended daily allowance) had a 55% reduction in risk of developing Alzheimer’s. Unfortunately, most people who reached that level did so by taking supplements, suggesting the difficulty of doing so through diet alone. Folates are abundant in foods such as liver, kidneys, yeast, fruits (like bananas and oranges), leafy vegetables, whole-wheat bread, lima beans, eggs and milk; however, they are often destroyed by cooking or processing. No association was found between vitamin C, carotenoids (such as beta-carotene) or vitamin B-12 intake and decreased Alzheimer's risk.
Results appear in the inaugural issue of Alzheimer's & Dementia: The Journal of the Alzheimer's Association. Full reference
http://www.eurekalert.org/pub_releases/2005-08/uoc--fme081105.htm

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.
The study appears in the August 24 issue of the Journal of Neuroscience. Full reference
http://www.eurekalert.org/pub_releases/2005-08/hhmi-bai082405.htm

Biosensor reveals new information about ADDLs

A new method using nanoscale optical biosensors allows researchers to detect and estimate the size and structure of ADDLs in cerebrospinal fluid. It’s believed that only ADDLs of a certain size cause problems for neurons in the early stages of Alzheimer’s disease. It is hoped that eventually this technology will help us diagnose Alzheimer’s accurately in living people, and aid our understanding of how ADDLs are involved in Alzheimer’s.
The findings were presented on August 31 at the 230th national meeting of the American Chemical Society. Reference
http://www.eurekalert.org/pub_releases/2005-08/acs-brn081905.htm

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July

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.
The results were published in the July 15 issue of Science. Full reference http://www.eurekalert.org/pub_releases/2005-07/uom-uom071105.htm

Early warning signs of Alzheimer's show up years before official diagnosis

A meta-analysis of 47 studies of Alzheimer's disease has revealed that people can show early warning signs across several cognitive domains years before they are officially diagnosed, confirming that Alzheimer's causes general deterioration and tends to follow a stable preclinical stage with a sharp drop in function. People at the preclinical stage showed marked preclinical deficits in global cognitive ability, episodic memory, perceptual speed, and executive functioning; along with somewhat smaller deficits in verbal ability, visuospatial skill, and attention. There was no preclinical impairment in primary memory. There is no clear qualitative difference between the normal 75-year old and a preclinical Alzheimer’s sufferer; instead it seems that the normal elderly person, the preclinical Alzheimer’s person, and the early clinical Alzheimer’s patient represent three instances on a continuum of cognitive capabilities.
The findings appeared in the July issue of Neuropsychology. Full reference
http://www.eurekalert.org/pub_releases/2005-07/apa-ews072505.htm

Missing eyeglasses impair activities for a third of nursing home patients with Alzheimer's disease

A study of nearly 100 Alzheimer’s patients in nursing homes has determined that one third of them were not using or did not have glasses that were strong enough to correct their eyesight. Apart from causing disorientation, limiting mobility and increasing the chance of falls, the loss of vision is likely to impact on mental stimulation, by making it difficult or impossible to engage in mentally stimulating activities such as reading or watching television.
The report appeared in the July/August issue of the Journal of the American Medical Directors Association. Full reference
http://www.eurekalert.org/pub_releases/2005-07/slu-mem071905.htm

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.
The study was published in the May issue of Annals of Neurology. Full reference
http://www.eurekalert.org/pub_releases/2005-07/thuo-afo072805.htm

New light on why plaques form

Alzheimer's disease is characterized by an increasing deposit of the amyloid-β protein in the brain, which collect to form aggregations called 'plaques'. New research has unraveled how certain plaques are formed. It seems the plaques attach primarily to blood vessels, which show clear structural damage, leading to leakage between the blood vessels and the brain. Under normal circumstances, the blood vessels transport excess amyloid-β protein away from the brain. The findings suggest new treatment approaches.
The report was published in the August issue of American Journal of Pathology. Full reference
http://www.eurekalert.org/pub_releases/2005-07/vfii-adn072705.htm

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