Clumps and tangles

Alzheimer's disease has been studied for nearly a century.

As Germany was enjoying an industrial boom before World War I, Alois Alzheimer, a neurologist in Munich, first identified the disease. He interviewed a woman who was losing her memory and spatial skills. Before she died a few years later, the woman had started hallucinating and had lost the ability to write.
Alzheimer performed an autopsy on her brain in 1906. He found protein plaques, clumps of tiny biological molecules, and also found that parts of the nerve cells in her brain had become tangled. Those clumps and tangles have come to define Alzheimer's disease.
Like Alzheimer, scientists today still do not know what causes the disease. Some believe the clumps and tangles are a result of Alzheimer's, not its cause. But many studies have shown that the clumps and tangles cause brain decay. Alzheimer's research is therefore often aimed at reducing the number of clumps in the brain.
There is no cure for Alzheimer's disease, nor is there a way to stop it from progressing. The few drugs that are available mostly help ease some symptoms of the disease, such as insomnia, anxiety and depression. The nationwide study now under way aims to determine whether lowering the cholesterol in Alzheimer's patients is enough to slow the progress of the disease by slowing the accumulation of clumps in the brain.
The clumps are formed from the biological molecules, called beta-amyloid particles, that float around in the brain. Because the particles are slightly sticky, they eventually start clinging to each other. Studies have shown that high levels of cholesterol can trigger the brain to produce lots of beta-amyloid particles, which occur naturally in the brain but become dangerous when clumped together -- ''Like when you are cooking spaghetti and it all sticks together,'' said William Seavey, a geriatrician and internist at UC-Davis who has also been involved in the nationwide study.
But at this point, Seavey said, "I wouldn't go out and take a cholesterol-lowering drug simply to prevent Alzheimer's disease. But I think there is a lot of reason to take care of your brain and your heart to avoid Alzheimer's."

Clinical observation on acupuncture combined with music for treatment of Alzheimer disease

Zhongguo Zhen Jiu. 2005 Jun;25(6):390-2
Authors: Liu G, Yuan LX

OBJECTIVE: To find the method for increasing clinical therapeutic effect on Alzheimer disease (AD).
METHODS: The patients of AD meeting American NINCDS-ADRDA Criteria were randomly divided into group A and group B. The group A (n = 21) were treated with acupuncture for 10 courses, 10 sessions constituting one course; and the group B (n = 20) were treated with combination of acupuncture and music therapy. The acupuncture method was the same as the group A and the music therapy was given for 20 sessions, once every 5 days. After treatment, their effectiveness were evaluated with the Mini-Mental State Examination (MMSE) and Activities of Daily Living (ADL).
RESULTS: After treatment, the scores for MMSE increased significantly (P < 0.05) and the scores for ADL decreased significantly (P < 0.05) in the both groups, and the therapeutic effect in the group A was better than the group B (P < 0.05).
CONCLUSION: Acupuncture combined with music therapy can increase the therapeutic effect on AD.

Korean Scientists Give Hope to Alzheimer Patients

A team of Korean scientists may have found a way to control Alzheimer's disease.

The team, led by Mook In-hee of Seoul National University Medical School, said Monday it found the protein that inhibits the harmful protein beta-amyloid, a cause of senile dementia. The controlling protein is called ERK1/2.
It is known that the enzymes beta-secretase and gamma-secretase are involved in the creation of beta-amyloid. Beta-secretase’s role in causing Alzheimer’s disease has been well known, and pharmaceutical giants worldwide have been trying to develop drugs to control the enzyme, to little avail.
Prof. Mook and her team discovered that ERK1/2 controls the function of gamma-secretase, and as a result, prevents creation of beta-amyloid. The discovery could open up a new way to treat senile dementia, the team said. In animal experiments, artificial control of the function of ERK1/2 sharply increased the amount of beta-amyloid produced. A treatment for Alzheimer’s disease would conversely have to boost the function of ERK1/2.
The research was conducted with financial support from the Ministry of Science and Technology, and the results were published in the Nov. 28 Journal of the Federation of American Societies for Experimental Biology.

Amyloid-beta: Acute-phase apolipoprotein with metal-binding activity.

J Alzheimers Dis. 2005 Nov;8(2):129-137
Authors: Kontush A

In monomeric form, amyloid-beta (Abeta), an amphipatic 4 kDa peptide which plays a key role in the pathogenesis of Alzheimer's disease (AD), is associated with lipoproteins in biological fluids and possesses high affinity to transition metal ions; in addition, synthesis of Abeta is upregulated under acute phase conditions. These data suggest that Abeta can be regarded as a normal physiological component of lipoproteins and may represent an acute-phase apolipoprotein with metal-binding activity. Interaction with transition metal ions may cause aggregation of Abeta, leading to formation of oligomers. Such oligomerised Abeta may lose its normal biological functions and acquire deleterious activities. To be efficient, novel anti-AD therapies should target oligomeric forms of Abeta while preserving the monomeric form of the peptide.
PMID: 16308481

Very Early Detection of Alzheimer Neuropathology and the Role of Brain Reserve in Modifying Its Clinical Expression.

J Geriatr Psychiatry Neurol. 2005 Dec;18(4):218-223
Authors: Mortimer JA, Borenstein AR, Gosche KM, Snowdon DA

Numerous studies show that the pathology of Alzheimer's disease is present decades before a clinical diagnosis of dementia can be made. Given the likelihood that agents will become available that reliably delay onset and/or slow progression of Alzheimer's disease, it will be important to detect preclinical Alzheimer's disease as early as possible for maximal treatment effect. Detection of individuals by sensitive cognitive measures provides one way to identify people who are at high risk of developing clinical Alzheimer's disease. However, it is likely that those with considerable brain or cognitive reserve will be able to mask cognitive deficits until very close to the onset of the dementia, rendering such cognitive measures insensitive. Optimum biomarkers for Alzheimer's disease therefore need to target the severity of underlying brain pathology independently of brain reserve. Findings are presented showing the importance of higher education and larger brain size in masking the underlying disease pathology.

Protein deposits may cause Alzheimer's

CHICAGO (AP) -- A new study supports the notion that certain protein deposits found in the brains of Alzheimer's victims are a cause of the mind-robbing disease, and not just a symptom. Autopsies on 79 nursing home patients confirmed that beta-amyloid protein plays a role in the earliest stages of Alzheimer's -- even before symptoms of dementia appear, the researchers reported in today's Journal of the American Medical Association. Sticky plaques of beta-amyloid in the brain and tangles of a protein known as tau inside brain nerve fibres are two of the distinguishing features of Alzheimer's. Scientists disagree over which feature may play a more central role in the destruction of brain cells. And some believe that the plaques and tangles are actually markers left by nerve cells killed by some other unknown cause. The study's authors favour the beta-amyloid theory because they found that the presence of beta-amyloid preceded development of tau protein in the brain's frontal cortex. In an accompanying editorial, Dr. Dennis J. Selkoe, a neurologist at Harvard's Brigham and Women's Hospital, called the conclusion exciting and said it could lead to new ways to diagnose and treat Alzheimer's. "This work, coupled with early work, clearly points to amyloid build-up as the cause," said Selkoe, who holds a stake in Elan Corp., which is testing a vaccine aimed at preventing beta-amyloid accumulation. But an executive at the Alzheimer's Association said the study does not prove what causes the disease. "What it doesn't tell us is which comes first, the chicken or the egg -- the disease or beta-amyloid," said William Theis, vice-president for medical and scientific affairs at the Alzheimer's Association. The authors, led by neuroscientist Jan Naslund of Rockefeller University in New York, studied autopsy results on 63 patients with mild to severe dementia believed to be caused by Alzheimer's and 16 mentally healthy patients. Increases of beta-amyloid in brain tissue were associated with increasing severity of mental decline, with the highest levels of beta-amyloid found in the brains of patients with the greatest degree of dementia. Abnormal beta-amyloid levels were also found even in patients without dementia. The researchers said those patients would have gone on to develop full-blown Alzheimer's had they lived. There were already significant levels of beta-amyloid found in early dementia patients with no tangles in the frontal cortex, said Dr. Joseph Buxbaum, a co-author and head of the molecular neuropsychiatry laboratory at Mount Sinai School of Medicine in New York. Buxbaum said that suggests beta-amyloid "must be a cause." Buxbaum said his study is a boost to research aimed at finding ways to block accumulation of beta-amyloid.

Similar Neurocognitive Performance of Adults With and Without a History of Parental

Alzheimer's Disease: A Pilot Study.
J Geriatr Psychiatry Neurol. 2005 Dec;18(4):208-212
Authors: Ercoli L, Siddarth P, Harrison T, Jimenez E, Jarvik LF

The first reported 20-year prospective follow-up of middle-aged children of Alzheimer patients failed to find statistically significant neurocognitive decline. Because that report did not include a comparison group, the current study compared the 20-year follow-up scores with scores obtained on the same 8 measures by an age-comparable sample of healthy adults without a family history of Alzheimer's disease. Both were convenience samples (n = 24). Statistical analyses (correcting for age) yielded no significant group differences in neurocognitive scores but did show a significantly higher mean score for the comparison group on the Mini-Mental State Examination (29.5 vs 28.8, P = .003, controlling for age).

Even though this finding suggests that adult children of a parent with Alzheimer's disease performed well on a limited neurocognitive battery and on the Mini-Mental State Examination, the findings are preliminary and require confirmation on large representative samples with appropriate controls and long-term follow-up.

New Paper Highlights ExonHit’s Novel Approach for the Treatment of Alzheimer’s Disease
Exonhit Therapeutics (FRANCE)

November 24, 2005 - Paris, France.
ExonHit Therapeutics, a drug and diagnostic discovery company, today announced that EHT 0206, one of its drug candidates, has shown promising new data in the treatment of Alzheimer’s disease. Preclinical studies of EHT 0206, published in the US peer reviewed magazine Journal of Biological Chemistry (J Biol Chem. 2005 Nov 11;280(45):37516-25), have shown that EHT 0206 has the potential not only to slow down the progression of the Alzheimer’s disease but can also change the course of the underlying disease.
The newly published data shows that EHT 0206 may decrease the formation of senile plaques in animal models. This is a key finding, as these plaques are thought to be responsible for the neuronal loss and consequent cognition impairment seen in Alzheimer’s patients. EHT 0206 is a small molecule that can be administered both orally and systemically which was synthesised in-house by ExonHit. These preliminary preclinical results also show that EHT0206 crosses the hemato-encephalic barrier to reach the brain and is well tolerated. “We are excited by the initial data that we have generated with EHT 0206.
The results that have been published today suggest that we have found a therapeutic approach to Alzheimer’s disease that major pharmaceutical companies have been looking for many years, a compound that is capable of reducing the formation of the senile plaques which are central to this devastating illness,” commented Bruno Tocqué, President of the Management Board of ExonHit. “Our new molecular series has the potential to significantly alter the course of this disease and we intend to evaluate it in human trials as quickly as possible. This will be our second clinical project with EHT0202 in this indication,” he added. By applying its unique DATAS technology on the brain tissue of patients with Alzheimer’s disease, ExonHit has been able to identify alterations in the Rac protein, which pinpointed out the possible essential role of the Rac protein in the development of the disease. It has been shown that alterations of Rac and its functionality in the brain increases production of beta-amyloid peptide (Aß, a key step in the formation of senile plaques. EHT 0206 blocks the activity of the Rac protein and the subsequent accumulation of the Aß which forms the senile plaques. ExonHit has filed patents for all the original chemical series showing activity on the Rac protein as well as their uses for various appropriate therapeutic indications, in particular Alzheimer’s disease.

Alzheimer's plaque precursor is imaged
CHICAGO, Nov. 22 (UPI)

University of Illinois-Chicago chemists have obtained the first molecular-level image of Alzheimer's precursors using a nuclear magnetic resonance system.
Scientists believe understanding the molecular structure of the bundled fibrils that form the brain plaques seen in Alzheimer's disease may help identify targets for new drugs to combat many neurodegenerative diseases.
Microscopic bundled fibrils made of proteins called amyloid-beta are presumed to be the toxic culprits in the senile plaques found in Alzheimer's patients' brains. But there's now increasing evidence even smaller assemblies of amyloid-beta found prior to formation of pre-fibrils are the real nerve-killers.
Researchers said electron microscope images of the nanometer-scale spherical assemblies failed to reveal any distinct molecular structure.
But now Yoshitaka Ishii, assistant professor of chemistry, and graduate student Sandra Chimon, determined the structure using a methodology developed with high-resolution solid-state nuclear magnetic resonance.
"This is the first case showing that these intermediate species, the smaller assemblies, have a well-defined structure," said Ishii.
Details were reported last month in the Journal of the American Chemical Society.

Previous psychiatric history as a risk factor for late-life dementia: a population-based case-control study.

Authors: Cooper B, Holmes C

OBJECTIVE: To test the hypothesis that risk for dementia in late life is increased by a history of earlier psychiatric illness, and to examine the specificity of any such association.

METHODS: Frequency of earlier treated psychiatric illness was established by record searches and informant histories for all persons aged over 60 who were entered on the Camberwell dementia case register over a 2-year period and for an individually matched control group of the local elderly population, drawn from the files of the area Family Health Services Authority.
RESULTS: Of 559 persons with a clinical diagnosis of dementia, 70 (12.5%) had a history of psychiatric illness long preceding, and apparently unrelated to, the onset of dementia. When these patients were compared with a matched comparison group of dementia register patients who had no recorded psychiatric history, the two groups appeared broadly similar in type of dementia, severity and clinical features. Sixty-three of the earlier psychiatric histories could be identified from the available medical records alone. Applying the same procedure to the matched control group of Camberwell residents yielded from the 559 only 19 (3.4%) with a history of treated psychiatric illness before the age of 70. The difference in case frequency between the two groups was highly significant and corresponded to an estimated odds ratio of 3.6. The increase in risk, which was not restricted to dementia of Alzheimer type, appeared to be characteristic of major psychiatric illness, rather than specific for depression.
CONCLUSION: There is a positive association between previous psychiatric history and late-life dementia which is of predictive significance. The underlying causal links merit further research.

Detecting Alzheimer's Early - Inside Science
2005
BACKGROUND: Researchers at Harvard Medical School have developed two optical tests that could potentially diagnose Alzheimer's disease in its beginning stages. The tests build upon a recent discovery that the presence of telltale proteins in the eye is an early sign of the disease. Such tests can improve patients' chances to start treatment earlier, and may also speed development of new drugs.
HOW IT WORKS: The same type of amyloid beta proteins which are a hallmark of Alzheimer's when found in the brain are also found in the lens and fluid of the eye. These proteins produce an unusual type of cataract in a different part of the eye than common cataracts (which are not associated with Alzheimer's). Scientists can detect these proteins by injecting a light-sensitive dye, then shining a laser onto the specific part of the lens where the cataracts tend to form. The molecules in the dye bind to the protein molecules, if they are present, and the light will cause the resulting molecules to glow. This technique is called quasi-elastic light scattering.
ABOUT ALZHEIMER'S: Alzheimer's is the most common form of dementia, a brain disorder that primarily affects the elderly. Scientists still aren't sure what causes the disease, and there is no cure. It is named after a German doctor, Alois Alzheimer, who noticed (in 1906) anomalies in the brain tissue of a woman who had died of a strange mental illness. There were abnormal clumps (called amyloid plaques) and tangled bundles of fibers, both of which are the most common signs of Alzheimer's. Other brain changes can occur. Nerve cells die in areas of the brain vital to memory and other mental abilities, and the connections between nerve cells are disrupted, impairing thinking and memory.
SYMPTOMS: Alzheimer's is a slow-moving disease, and in its earliest stages, may merely appear to be mild forgetfulness, and confused with age-related memory change. There may be problems remembering recent events or activities, or the names of familiar people or objects. As the disease progresses, the forgetfulness becomes more severe, interfering with daily activities, such as brushing one's teeth. There are problems speaking, understanding, reading or writing, and eventually the brain damage becomes so severe as to require total care.

Test finds evidence of early-stage Alzheimer's
Scientists hope examination of brain, spinal fluid can help diagnose disease

By Tina Hesman
St. Louis Post-Dispatch
November 20, 2005

WASHINGTON -- Alzheimer's disease starts years or even decades before symptoms begin. Now scientists at Washington University and the University of Pittsburgh say they can see evidence of the disease in the brains and spinal fluid in people in the early stages of dementia and in a few people who don't yet have memory problems.
Anne M. Fagan Niven, a researcher at Washington University, presented the results of the universities' joint study this past week at the annual meeting of the Society for Neuroscience.

The technique is not yet available in the doctor's office, Fagan said, but the researchers are moving closer to being able to detect Alzheimer's disease before brain cells start to die.
Initially, the test could be used to monitor experimental drugs and determine whether a person with memory problems has Alzheimer's disease or another brain defect. Eventually, the test or similar measures could be used to identify people at risk of developing the disease who could benefit from treatments to stop or slow brain cell death.
Fagan and her colleagues examined two dozen people, including some in the early stages of dementia and some with no symptoms of disease. The researchers drew fluid from the volunteers' spinal columns and probed the fluid to determine the levels of a protein called Amyloid-beta 42, which also is known as A-beta 42.
The protein builds up in brains of people with Alzheimer's disease and forms plaques. The plaques kill brain cells, producing memory loss.
In people without Alzheimer's disease, the protein is made in the brain, gets dumped into the spinal fluid and is flushed into the blood for disposal. But when the protein begins to build up in the brain, more A-beta gets absorbed into plaques, leaving less to reach the spinal fluid, Fagan said.
She and her colleagues found that people with symptoms of Alzheimer's disease had low levels of the A-beta 42 protein in their spinal fluid.
The scientists also used a compound, called PIB, which helps researchers detect plaques during brain scans. As expected, Fagan found that the people with dementia and low levels of the protein in spinal fluid also had A-beta 42 plaques in their brains.
But three people who didn't show any symptoms of Alzheimer's disease also had low A-Beta 42 levels in their spinal fluid and plaques in their brains. The researchers are tracking the volunteers to find out whether they will develop the disease.
Fagan cautioned that the only definitive test for Alzheimer's disease is still a brain autopsy.

Obesity in middle age and future risk of dementia
Dietary fat and sugar may hold the clue

BMJ 2005;331:454-455 (20 August)

EDITOR—Whitmer et al report further evidence supporting the association between obesity and dementia.1 Although the mechanism is still far from being understood, the authors alluded to the involvement of adiposity with inflammation and its markers.
One possible mechanism linking obesity with dementia is oxidative stress resulting from an increased intake of processed sugars and fats, which is the hall-mark of the modern diet. Rats maintained on a diet high in refined sugar and fat generated higher concentrations of free radicals.2 3 In contrast, caloric restriction in animals leads to reduced production of free radicals by mitochondria and increased longevity.4
Whitmer et al acknowledge that the lack of nutritional assessment was a limitation of their study. If such data had been available they would have shed light specifically on a possible relation between fat and sugar intake and risk of dementia, especially as a diet rich in these substances is linked to obesity. We recently showed that patients with dementia eating a diet high in fat and carbohydrates have an increased blood activity of glutathione peroxidase, an endogenous antioxidant, which may be a compensatory response to an increased oxidative stress in dementia.5
Whitmer et al say that all cause dementia diagnoses included dementia, Alzheimer's disease, and vascular dementia.1 However, their data did not include differentiation between these subsets, especially between Alzheimer's disease and vascular dementia. Whether obesity was preferentially associated with either vascular dementia or Alzheimer's disease, or both, would be interesting, especially as the neuropathological aetiology of these two disorders is different.

Regulatory aspects of vascular dementia in the United States.

Oliva A, Mani R, Katz R.

Division of Neuropharmacological Drug Products, US Food and Drug Administration, Rockville, MD 20857, USA. oliviaa@cder.fda.gov

There is significant interest in the development of new drugs to treat vascular dementia. However, before US approval of new drugs for this entity is possible, certain issues with regulatory implications need to be addressed. Is vascular dementia a distinct clinical syndrome with valid diagnostic criteria? Can this entity be distinguished from Alzheimer's disease (AD) and other causes of dementia? What design features are important for clinical trials in this disorder? The US Food and Drug Administration (FDA) convened a special meeting of the Peripheral and Central Nervous System Advisory Committee in an attempt to answer these questions. The conclusions from this meeting indicate that vascular dementia (VaD) is a pathologically heterogeneous disorder but appears to be reasonably distinguishable from AD dementia. The NINDS-AIREN diagnostic criteria are suitable as entry criteria for vascular dementia trials. Trials should be similar in duration to AD dementia trials and should employ a dual outcome strategy (cognitive + global/functional measures). For drugs that are believed to have a disease-modifying effect, clinical trials should study specific vascular dementia subtypes and would need to employ substantially different designs from those used currently. The term "vascular dementia" may not be entirely appropriate to describe this population.

Leisure-time physical activity at midlife and the risk of dementia and Alzheimer's disease.

Lancet Neurol. 2005 Nov;4(11):705-11

Authors: Rovio S, Kåreholt I, Helkala EL, Viitanen M, Winblad B, Tuomilehto J, Soininen H, Nissinen A, Kivipelto M

BACKGROUND: Physical activity may help maintain cognitive function and decrease dementia risk, but epidemiological findings remain controversial. The aim of our study was to investigate the association between leisure-time physical activity at midlife and the subsequent development of dementia and Alzheimer's disease (AD).
METHODS: Participants were randomly selected from the survivors of a population-based cohort previously surveyed in 1972, 1977, 1982, or 1987. 1449 persons (72.5%) age 65-79 years participated in the re-examination in 1998 (mean follow-up, 21 years). 117 persons had dementia and 76 had AD. Multiple logistic regression methods were used to analyse the association between leisure-time physical activity and dementia or AD.
FINDINGS: Leisure-time physical activity at midlife at least twice a week was associated with a reduced risk of dementia and AD (odds ratio [OR] 0.48 [95% CI 0.25-0.91] and 0.38 [0.17-0.85], respectively), even after adjustments for age, sex, education, follow-up time, locomotor disorders, APOE genotype, vascular disorders, smoking, and alcohol drinking. The associations were more pronounced among the APOE epsilon4 carriers.
INTERPRETATION: Leisure-time physical activity at midlife is associated with a decreased risk of dementia and AD later in life. Regular physical activity may reduce the risk or delay the onset of dementia and AD, especially among genetically susceptible individuals.

Alzheimer's disease, brain imaging studies reveal clues to its progression

Category: Alzheimer's News

Article Date: 20 Nov 2005

A novel imaging agent heralded for its potential to diagnose Alzheimer's disease during life is now giving researchers information never before available about how and where the disease progresses in the brain. Results of this new research involving Pittsburgh Compound-B (PIB) - which binds to the telltale beta-amyloid deposits in the brain of Alzheimer's patients - were presented by University of Pittsburgh researchers today at Neuroscience 2005, the 35th Annual Meeting of the Society for Neuroscience, being held Nov. 12-16 in Washington, D.C.

Hallucinations and Mortality in Alzheimer Disease.
Am J Geriatr Psychiatry. 2005 Nov;13(11):984-990

Authors: Wilson RS, Krueger KR, Kamenetsky JM, Tang Y, Gilley DW, Bennett DA, Evans DA

OBJECTIVE: The authors tested the relationship of hallucinations and delusions to mortality in Alzheimer disease (AD).
METHODS: A group of 407 persons with clinically diagnosed AD completed a uniform clinical evaluation, after which vital status was monitored for a mean of 3.7 years. At the initial evaluation, a previously established, structured, informant interview was used to ascertain the presence of hallucinations and delusional thinking. The evaluation also included a structured medical history, inspection of all medications, and detailed assessment of cognitive functioning and parkinsonian signs.
RESULTS: At study onset, hallucinations were present in 41.0% of participants and delusions in 54.4%. During follow-up, 146 deaths occurred. In a proportional-hazards model adjusted for age, sex, race, and education, hallucinations were associated with a 78% increase in risk of death. The association was not substantially altered in subsequent analyses that controlled for level of cognitive impairment, severity of parkinsonism, use of antipsychotic medications, and the presence of chronic medical conditions. Risk of death was more than doubled in those with both auditory and visual hallucinations. By contrast, we did not find evidence of an association of delusions with mortality.
CONCLUSION: Hallucinations are associated with an increased risk of death in AD.

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

Alzheimer's NewsArticle Date: 19 Nov 2005
Cholesterol lowering drugs, including statins, may slow the progression of Alzheimer's disease, concludes a study in the Journal of Neurology Neurosurgery and Psychiatry. The research team assessed the degree of brain function loss caused by Alzheimer's disease in 342 patients attending a memory clinic. They then monitored the progress of the disease for almost three years. The average age of the patients was 73. Most were women. In all, 129 patients had abnormal cholesterol levels, almost half of whom were being treated exclusively with statins. Of the remainder, 105 had abnormal untreated cholesterol , and 108 had normal cholesterol levels. Drug treatment included fibrates or statins, or a mixture of both. During the three years, all the patients deteriorated, but the disease progressed significantly more slowly in the patients given cholesterol lowering drugs. Progression of the disease was rated at 1.5 points a year in those given the drugs, 2.4 in those whose cholesterol was not treated, and 2.6 in those with normal cholesterol levels. The risk factor profile for Alzheimer's disease, including high blood pressure and diabetes, scarcely differed between the two groups with abnormal cholesterol levels. The authors conclude that cholesterol lowering drugs may effectively slow progression of Alzheimer's disease, but suggest that a large trial will be needed to confirm their findings. An accompanying editorial argues that it is still too early to definitively conclude that cholesterol lowering treatment is a valid option for patients with Alzheimer's disease. The editorial also points out that the research was not able to isolate the potential advantages of the drugs other than their ability to lower cholesterol. Lipid lowering agents are associated with a slower cognitive decline in Alzheimer's disease, J Neurol Neurosurg Psychiatry 2005; 76: 1624-9Teresathagan@bma.org.ukBMJ Specialty Journalshttp://www.bmj.com/

Hypertension and cognition.

Int Psychogeriatr. 2003;15 Suppl 1:139-46
Authors: Skoog I
Hypertension is a risk factor for stroke, ischemic white-matter lesions, cardiovascular disorders, and vascular dementia. This risk increases with increasing blood pressure. Several studies report that high blood pressure precedes Alzheimer's disease (AD) by decades, but blood pressure decreases the years before dementia onset and is lower in individuals with AD than in controls. High blood pressure has also been related to the neuropathological manifestations of AD. The exact mechanism behind these associations is not clear. Hypertension may cause cerebrovascular disease that may increase the likelihood that individuals with AD encephalopathy will express a dementia syndrome, this may accelerate the AD process, subclinical AD may lead to increased blood pressure, and similar biological mechanisms may be involved in the pathogenesis of both disorders. Hypertension is a common disorder and often untreated. Even if hypertension results only in a moderately increased risk of AD, or overall dementia, better treatment of hypertension may have an immense effect on the total number of individuals with dementia.

Exercise and cognitive function

Helen Petrovitch, Lon White
The evidence for a protective effect of moderate
exercise on cognitive decline in elderly people is
growing. Continued moderate exercise in elderly
individuals has many other health benefits and is part of
a healthy lifestyle. Further research is needed to examine
mechanisms that underlie the apparently ameliorating
effect of exercise on ageing-related brain disease, the
relative value of different forms of exercise, and the
associations of duration and intensity of exercise with
healthy brain ageing.

The Honolulu-Asia Aging Study, Pacific Health Research Institute,
and Kuakini Medical Center, Honolulu, HA, USA

Vitamin E Supplementation in Alzheimer's Disease, Parkinson's Disease, Tardive Dyskinesia, and Cataract

Ann Pharmacother. 2005 Nov 15;
Authors: Pham DQ, Plakogiannis R
We encourage patients to supplement with vitamin E-rich foods. The use of a daily multivitamin, which usually contains 30 IU of alpha-tocopherol, may be beneficial; however, we discourage individual vitamin E supplements that usually contain 400 IU of alpha-tocopherol.

Vasogen's VP025 Prevents Detrimental Effects of Beta-amyloid

November 17, 2005
TORONTO, Nov. 17 /PRNewswire-FirstCall/ -- Vasogen Inc. (NASDAQ:VSGN; TSX:VAS), a leader in the research and commercial development of technologies targeting chronic inflammation underlying cardiovascular and neurological disease, announced that new preclinical data presented yesterday at Neuroscience 2005, the Society for Neuroscience's 35th Annual Meeting in Washington, DC, demonstrates the ability of VP025 to prevent the detrimental neurological effects of chronic beta-amyloid exposure in a model of Alzheimer's disease."We believe that the data presented, demonstrating the ability of VP025 to preserve memory and learning function in the presence of chronic beta- amyloid exposure, provides further evidence supporting the potential of VP025 as a new treatment for Alzheimer's and other dementias," stated Dr. Anthony Bolton, Vasogen's Chief Scientific Officer. "Having successfully completed our phase I program, we look forward to moving VP025 into phase II clinical development in neuro-inflammatory disease."Beta-amyloid is the major component of the plaques found in brains of Alzheimer's disease patients and is implicated in the development and progression of this condition. Beta-amyloid has also been linked to increased activation of microglial cells (inflammatory immune cells in the brain) and reduced memory and learning function. The results presented today by Dr. Marina Lynch's team from the Trinity College Institute of Neuroscience, Dublin, Ireland, demonstrate that VP025 both prevented microglial activation and preserved memory and learning function during chronic infusions of beta-amyloid.Yesterday, Vasogen also announced that two additional presentations of preclinical data at Neuroscience 2005 demonstrated the impact of VP025 on key inflammation-signaling pathways. VP025 was shown to inhibit p38 MAP kinase, a key component of the inflammation-signaling pathway, regulating IL-1, TNF-alpha, and other immune system responses associated with many inflammatory conditions. In a separate model demonstrating the association of aging with increased inflammation in the central nervous system, VP025 was shown to increase CD200, a protein that controls inflammation and maintains microglial cells in an un-activated state.Many neurological conditions are associated with an inflammatory response in the nervous system, including Alzheimer's disease, Parkinson's disease, and ALS (also known as Lou Gehrig's disease). These conditions are characterized by increased levels of inflammatory mediators, including cytokines, leading to the death of nerve cells and the eventual loss of functional activity. Due to the prevalence, morbidity, and mortality associated with neuro-inflammatory diseases, they represent a significant medical, social, and financial burden.

Spinal Tap for Alzheimer's Diagnosis

November 17, 2005
Filed under: Neurology
The AP is reporting on Washington University professor Anne Fagan Niven's ">new diagnostic approach to Alzheimer's:
Researchers examined two dozen people, including some in the early stages of dementia and some with no symptoms of disease. They drew fluid from the volunteers' spinal columns and determined the levels of a protein called Amyloid-beta 42 in the fluid.
The protein builds up in brains of people with Alzheimer's disease and forms plaques, which kill brain cells, producing memory loss and other disease symptoms.
Researchers found that people with symptoms of Alzheimer's disease had low levels of the A-beta 42 protein in their spinal fluid.
Fagan Niven's team also used PIB to detect plaques on CT scans. Significantly, a few patients were found with low A-beta 42, and brain plaques, but no signs of congnitive decline. They're being followed closely.
In general, there's a huge thrust to slow Alzheimer's progression while patients still have good mental function. This technique is based on the simple spinal tap, with a twist. Yet it's not as well-defined.

Timing possible treatments against Alzheimer's disease
17 Nov 2005
Alzheimer Disease (AD) is characterized by hallmark lesions called amyloid plaques in the brain. The plaques are formed by the aggregation of small peptides (proteins), called amyloid beta peptide (Abeta), that are produced when a larger protein called amyloid precursor protein (APP) is cleaved by the action of two enzymes, beta-APP cleaving enzyme and gamma-secretase. Many scientists are developing inhibitors of these enzymes as possible therapies. In the meantime, other researchers are trying to test whether and how such approaches might work, at least in principle. Joanna Jankowsky, David Borchelt, and colleagues from institutes across the country, including Johns Hopkins School of Medicine, the Mayo Clinic Jacksonville, the National Cancer Institute, University of Florida, and the California Institute of Technology have some answers. As they report in the international open-access medical journal PLoS Medicine, they have engineered mice to continuously produce Abeta in their brains. The production can be switched off by giving the mice the antibiotic tetracycline in their drinking water. This switch-off at a certain point is similar to what would happen to human patients who would receive enzyme inhibitors once diagnosed with AD. Without tetracycline, the brains of the mice at six months of age are loaded with amyloid plaques. When the researchers switched the system off after some initial plaques had formed, they found two things: the existing plaques didn't grow or spread to other areas of the brain, but they did not go away either. As always, results from animal models cannot simply be extrapolated to human disease. However, this study suggests that treatment with drugs that lower production of Abeta can prevent progression of AD but not reverse the disease. While overall encouraging, the results emphasize the importance of early treatment with drugs that inhibit Abeta production. Citation: Jankowsky JL, Slunt HH, Gonzales V, Savonenko AV, Wen JC, et al. (2005) Persistent amyloidosis following suppression of Ab production in a transgenic model of Alzheimer disease. PLoS Med 2(12): e355. SOURCE: http://www.plosmedicine.org/

New test may detect Alzheimer's before it shows

BY TINA HESMANSt. Louis Post-Dispatch
WASHINGTON - Alzheimer's disease starts years or even decades before symptoms begin. Now scientists at Washington University and the University of Pittsburgh say they can see evidence of the disease in the brains and spinal fluid in people in the early stages of dementia and in a few people who don't yet have memory problems.
Anne M. Fagan Niven, a researcher at Washington University, presented the results of the universities' joint study Tuesday at the annual meeting of the Society for Neuroscience.
The technique is not yet available in the doctor's office, Fagan said, but the researchers are moving closer to being able to detect Alzheimer's disease before brain cells start to die. Initially, the test could be used to monitor experimental drugs and help determine whether a person with memory problems has Alzheimer's disease or another brain defect. Eventually, the test or similar measures could be used to identify people at risk of developing the disease who could benefit from treatments to stop or slow brain cell death.
Fagan and her colleagues examined two dozen people, including some in the early stages of dementia and some with no symptoms of disease. The researchers drew fluid from the volunteers' spinal columns and probed the fluid to determine the levels of a protein called Amyloid-beta 42, which is also known as A-beta 42.
The protein builds up in brains of people with Alzheimer's disease and forms plaques. The plaques kill brain cells, producing memory loss and other symptoms of the disease.
In people without Alzheimer's disease, the protein is made in the brain, gets dumped into the spinal fluid and is finally flushed into the blood for disposal. But when the protein begins to build up in the brain, more A-beta gets absorbed into plaques leaving less to reach the spinal fluid, Fagan said.
She and her colleagues found that people with symptoms of Alzheimer's disease had low levels of the A-beta 42 protein in their spinal fluid.
The scientists also used a compound, called PIB, which helps researchers detect plaques during brain scans. Collaborators at the University of Pittsburgh developed the compound.
As expected, Fagan found that the people with dementia and low levels of the protein in spinal fluid also had A-beta 42 plaques in their brains.
But three people who didn't show any symptoms of Alzheimer's disease also had low A-Beta 42 levels in their spinal fluid and plaques in their brains. The researchers are tracking the volunteers to find out whether they will eventually develop the disease.
Fagan cautioned that the only definitive test for Alzheimer's disease is still a brain autopsy.
The test will likely undergo many revisions and improvements but could be useful for diagnosing or ruling out Alzheimer's disease and screening people at risk of the disease once drugs to treat it are available.

Flurizan Reverses Disease Course and Improves Cognitive Function in Follow-on

SALT LAKE CITY, Nov. 15 /PRNewswire-FirstCall/ -- Myriad Genetics, Inc. (Nasdaq: MYGN - News; http://www.myriad.com/) announced today that an analysis of data from its Phase 2 follow-on study of Flurizan(TM) in patients with mild Alzheimer's disease showed that study participants improved as a group, regaining cognitive ability from months 12 through 18. Results of the 6-month follow-on study were presented today at the Neuroscience 2005 meeting in Washington, D.C., by Sandra E. Black, M.D., Professor of Neurology at the University of Toronto and lead investigator in Canada for the Phase 2 trial of Flurizan in patients with Alzheimer's disease.

3-D Structure of Alzheimer's Disease Filament Sho...

3-D Structure of Alzheimer's Disease Filament Shows How It Zips Up Peptides
LibrariesScience News

Researchers have solved the three dimensional structure of the long thread-like fibers that fill the brains of Alzheimer's disease patients. The structure reveals the proteins that make up the fibrils lock onto each other much like a zipper on a jacket.
Newswise — Researchers have solved the three dimensional structure of the long thread-like fibers that fill the brains of Alzheimer's disease patients. The structure reveals the proteins that make up the fibrils lock onto each other much like a zipper on a jacket. This advance, reported in the Nov. 14th early online edition of Proceedings of the National Academy of Sciences (PNAS), helps illuminate the molecular roots of Alzheimer's and possibly other degenerative diseases of the brain.
“Now that we understand at an atomic level how these fibrils form, it might help researchers develop a biomarker test to diagnose Alzheimer's disease at an early stage, as well as drugs to treat it,” says the study's lead investigator, Salk Institute for Biological Studies scientist Roland Riek, Ph.D., who collaborated with researchers at the University of Lausanne and Roche pharmaceuticals, both in Switzerland
As a result of the study, Riek and his colleagues may now understand how a potential Alzheimer's disease medication now in clinical trials in Europe reacts to the fibril. The drug binds to the end of the fibril chain of beta amyloid proteins, halting their lethal accumulation, an early step in the formation of the amyloid plaque deposits that are a hallmark of Alzheimer's.
Solving the structure of these fibrils may also offer insights into other neurodegenerative diseases such as Parkinson's disease and Creutzfeldt-Jacok disease that develop fibrils due to errant changes in the structural shape of brain proteins, adds Riek, assistant professor in Salk's Structural Biology laboratory.
“There are more than a dozen of these diseases, and what we learn from one offers us insights into others,” he says. For example, Riek and his colleagues described in the June 8 issue of Nature how such a conformational change turns tiny protein particles into the infectious molecules known as prions that are responsible for “mad cow disease,” and they also showed how that process could be reversed.
The research team of the Salk Institute in collaboration with the University of Lausanne and Roche, developed new research techniques to determine the 3D structure that mimics the most common type of fibrils found in patients with the disease.
They discovered that beta amyloid proteins (peptides) that make up these fibrils attach to each other on one end with an ever-growing property.
“From this structure we can nicely see what happens physically, where the fibril forms a template on which to bind other amyloid peptides in an inter-collated way,” Riek says. “The way these peptides lock on to each other is like a zipper on a jacket.” Due to the ever-growing property the zipper binds more and more loose peptides together to produce dense “plaque” filaments that may be toxic to the functioning of brain nerve cells.
In Alzheimer's disease, amyloid plaque form when enzymes cleave the amyloid precursor protein (APP), thereby releasing the toxic beta amyloid fragments. Healthy brains can clear away excess beta amyloid peptides, but for reasons that are not understood, these proteins, made up of between 39-42 amino acids, change shape in some people, leading to a sticky aggregation.
Riek already demonstrated how the flexible peptide can be altered, and in this study, he showed how a clump of them can attract and bind other molecules. “There are at least four stages needed to get to the point where a structure is created that can form filaments, and what we show here is that end stage.
Scientists are debating whether these long filaments produce the nerve damage that results in dementia, or whether the shorter, more mobile threads, which are also composed of beta amyloid. Riek and his team are now working on solving the 3D structure of these smaller aggregates, in their quest to sculpture the molecular roots of Alzheimer's disease.
Collaborating with Riek in the study, funded by Pew Charitable Trusts, were Thorsten Luhrs, Ph.D., postdoctoral researcher in the Structural Biology Laboratory, and Dave Schubert, Ph.D., Professor and head of Salk's Cellular Neurobiology Lab.
The Salk Institute for Biological Studies in La Jolla, California, is an independent nonprofit organization dedicated to fundamental discoveries in the life sciences, the improvement of human health and the training of future generations of researchers. Jonas Salk, M.D., whose polio vaccine all but eradicated the crippling disease poliomyelitis in 1955, opened the Institute in 1965 with a gift of land from the City of San Diego and the financial support of the March of Dimes.

Meditation associated with structural changes in brain MRI images show thickening of attention-related areas, potential reduction of aging effects

BOSTON - November 11, 2005
The regular practice of meditation appears to produce structural changes in areas of the brain associated with attention and sensory processing. An imaging study led by Massachusetts General Hospital (MGH) researchers showed that particular areas of the cerebral cortex, the outer layer of the brain, were thicker in participants who were experienced practitioners of a type of meditation commonly practiced in the U.S. and other Western countries. The article appears in the Nov. 15 issue of NeuroReport, and the research also is being presented Nov. 14 at the Society for Neuroscience meeting in Washington, DC. "Our results suggest that meditation can produce experience-based structural alterations in the brain," says Sara Lazar, PhD, of the MGH Psychiatric Neuroimaging Research Program, the study's lead author. "We also found evidence that meditation may slow down the aging-related atrophy of certain areas of the brain." Studies have shown that meditation can produce alterations in brain activity, and meditation practitioners have described changes in mental function that last long after actual meditation ceases, implying long-term effects. However, those studies usually examined Buddhist monks who practiced meditation as a central focus of their lives. To investigate whether meditation as typically practiced in the U.S. could change the brain's structure, the current study enrolled 20 practitioners of Buddhist Insight meditation - which focuses on "mindfulness," a specific, nonjudgmental awareness of sensations, feelings and state of mind. They averaged nine years of meditation experience and practiced about six hours per week. For comparison, 15 people with no experience of meditation or yoga were enrolled as controls. Using standard MRI to produce detailed images of the structure of participants' brains, the researchers found that regions involved in the mental activities that characterize Insight meditation were thicker in the meditators than in the controls, the first evidence that alterations in brain structure may be associated with meditation. They also found that, in an area associated with the integration of emotional and cognitive processes, differences in cortical thickness were more pronounced in older participants, suggesting that meditation could reduce the thinning of the cortex that typically occurs with aging. "The area where we see these differences is involved in both the modulation of functions like heart rate and breathing and also the integration of emotion with thought and reward-based decision making - a central switchboard of the brain," says Lazar. An instructor in Psychology at Harvard Medical School, she also stresses that the results of such a small study need to be validated by larger, longer-term studies. The study was supported by grants from the National Institutes of Health, the MIND Institute and the Centers for Disease Control and Prevention. Co-authors are Rachel Wasserman, Doug Greve, PhD, Michael Treadway, Brian Quinn, Scott Rauch, MD, and Bruce Fischl, PhD, of the MGH; Catherine Kerr, PhD, Harvard Medical School; Jeremy Gray, PhD, Yale University; Metta McGarvey, Harvard Graduate School of Education; Jeffery Dusek, PhD, and Herbert Benson, MD, Beth Israel Deaconess Medical Center and Mind/Body Medical Institute; and Christopher Moore, PhD, Massachusetts Institute of Technology and McGovern Institute for Brain Research. Massachusetts General Hospital, established in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of nearly $500 million and major research centers in AIDS, cardiovascular research, cancer, cutaneous biology, medical imaging, neurodegenerative disorders, transplantation biology and photomedicine. In 1994, MGH and Brigham and Women's Hospital joined to form Partners HealthCare System, an integrated health care delivery system comprising the two academic medical centers, specialty and community hospitals, a network of physician groups, and nonacute and home health services.

Another reason to drink red wine

By 24 HOURS NEWS SERVICES
Having another glass of red wine or eating more red grapes may be the key to keeping Alzheimer's from developing, a new study suggests.
The study says that a natural compound called resveratrol found in red wine, red grapes, peanuts and berries may work to prevent Alzheimer's from building up in the brain.
"This finding is a starting point where we may be able to isolate resveratrol and develop a drug to treat Alzheimer's," said study author Dr. Philippe Marambaud, a scientist at Litwin-Zucker Research Center for the Study of Alzheimer's Disease and Memory Disorders in Manhasset, New York.
Resveratrol works with other anti-oxidants to slow the neuro-degenerative process in humans.
"There are more than 600 different compounds identified in red wine, and the resveratrol works in combination with them," Marambaud said.
Marambaud said the polyphenol compound is found in high concentrations in red wines. The highest concentration of resveratrol has been reported in wines prepared from Pinot Noir grapes. Generally, white wines contain one per cent to five per cent of the resveratrol content in most red wines.
One of the features of Alzheimer's disease is the buildup of amyloid-beta peptides in the brain.
In the lab, Marambaud added resveratrol to cells which produce human amyloid-beta and tested the compound's effectiveness by monitoring amyloid-beta levels inside and outside the cells. They found that levels of amyloid-beta in the treated cells were much lower than those in untreated cells.

Think tank

By Graeme O'NeillNovember 14, 2005
AdvertisementAdvertisement
Remember this
It's early days, but baby boomers approaching the high-risk age for Alzheimer's might keep an eye on an experimental drug being developed by Melbourne company Prana Biotechnology.
Healthy young human volunteers in a just-completed phase I trial in Holland showed no adverse reaction to Prana's PBT2. Also, the drug enters the brain more readily - by a factor of 20 - than Prana's first-generation compound, the discarded antibiotic clioquinol.
Early tests with clioquinol showed the metal-chelating molecule traps and removes the copper and zinc ions that cause a toxic protein, beta amyloid, to aggregate in brain tissues. It quenches the oxidising reactions that kill neurons en masse.
Clioquinol dramatically improved the performance of transgenic mice with Alzheimer's in maze tests. It also reduced serum levels of beta amyloid in humans with advanced Alzheimer's and markedly slowed their cognitive decline - a first for any AD drug.
Excuse me!
Intense selection for desirable physical and production traits is still driving rapid evolution in modern livestock breeds, in surprising ways. Hamilton, New Zealand company Dexcel is trying to reduce methane from dairy herds. The average NZ Holstein-Friesian dairy cow belches 35 litres of the potent greenhouse gas daily, produced by microbial fermentation in the rumen, the large foregut chamber in all ruminants.
Dexcel researcher Dr Gary Waghorn says halving this loss of dietary energy could increase milk yield by up to 8 per cent.
Waghorn recently discovered why NZ's Holstein-Friesians eclipse their northern hemisphere progenitors in milk production. Farmers and breeders, through intense selection for fast eaters and high productivity, unwittingly doubled the breed's rumen capacity and changed its behaviour. Rather than eat and digest on the fly, Kiwi cows pack it away by day, and sleep on it.

Driving and Alzheimer's disease

Psychol Neuropsychiatr Vieil. 2005 Sep;3(3):163-8
Authors: Roche J
Although most aged people remain safe drivers, a greater risk for crashes due to medical conditions is observed in the elderly. Impairment of important functions for safe driving such as visuospatial skills, attention, memory and judgement are observed in dementia, particularly in Alzheimer's disease. The accident rate increases from 9.4 accidents per million vehicle kilometers traveled for 80 to 85 year-old drivers, but raises to 163.6 for drivers with moderate AD. Patients and their families should be informed that patients with mild dementia related to Alzheimer's disease (stage 1 on the Clinical Dementia Rating, CDR), have a substantially increased rate of traffic accidents and therefore should not drive. But subjects in the pre-dementia phase (stage 0.5 at the CDR, mild cognitive impairment) also pose significant driving safety problems. In most States of the USA, and many European countries, but not in France, law requires regular investigating of driving performance in the elderly.

Writing, aging and Alzheimer's disease

Psychol Neuropsychiatr Vieil. 2005 Sep;3(3):183-97
Authors: Croisile B
Writing is a complex and fragile cognitive function, that appeared very late in the history of mankind, and that also develops quite late in individuals. Aging does not induce changes in the lexical, semantic and syntaxic parameters of the writing description of a complex image. In the same way, spelling is not significantly altered through aging. Spelling errors are rare among seniors: they only concern infrequent words and mostly respect their pronunciation. The most frequent errors are about accents or double letters. Margins get smaller, seniors raise their pens less often and the pressure and width of writing decrease with age. Writing get progressively disorganized during Alzheimer's disease. The content of texts is primarily affected, texts becoming shorter and less coherent. Then, spelling is altered by regularization errors which are an evidence of lexical agraphia. Then, lexical agraphia gets worse and rapidly becomes mixed, combining lexical and phonological features. Finally, dementia worsens along with a massive deterioration of graphic features and spatial organization. Agraphia of Alzheimer's disease comes from a progressive and hierarchized disorganization of the various components of language and writing, due to the brain lesions in several associative areas, i.e. the parietal, temporal, occipital and frontal regions.

Benefits of fatty fish on dementia risk .

Neurology. 2005 Nov 8;65(9):1409-14
Authors: Huang TL, Zandi PP, Tucker KL, Fitzpatrick AL, Kuller LH, Fried LP, Burke GL, Carlson MC
OBJECTIVE: To compare associations of lean fish vs fatty fish (tuna or other fish) intake with dementia, Alzheimer disease (AD), and vascular dementia (VaD) .
METHODS: Fish intake was assessed by food frequency questionnaires. Incident dementia, AD, and VaD were determined through a series of cognitive tests, physician's assessment, and committee consensus.
RESULTS: Although consumption of lean fried fish had no protective effect, consumption of fatty fish more than twice per week was associated with a reduction in risk of dementia by 28% (95% CI: 0.51 to 1.02), and AD by 41% (95% CI: 0.36 to 0.95) in comparison to those who ate fish less than once per month. Adjustment by education and income attenuated the effect.
CONCLUSION: In the Cardiovascular Health Cognition Study, consumption of fatty fish was associated with a reduced risk of dementia and Alzheimer disease.

Alzheimer's Overview
Alzheimer's Disease is the most common cause of dementia in older people. It's a medical condition that disrupts the way the brain works.
AD affects the parts of the brain that control thought, memory and language. Although the risk of getting the disease increases with age, it is not a normal part of aging. The cause of the disease is unknown and there is no cure.
It is estimated that currently 4 million people in the United States may have Alzheimer's disease. The disease usually begins after age 65; the risk of AD goes up with age.
While younger people may have the disease, it is much less common. About 3 percent of men and women ages 65-74 have AD and nearly half of those over age 85 could have the disease.
AD is named after Dr. Alois Alzheimer, a German psychiatrist. In 1906, Dr. Alzheimer described changes in the brain tissue of a woman who had died of an unusual mental illness.
He found abnormal deposits (now called senile or neuritic plaques) and tangled bundles of nerve fibers (now called neurofibrillary tangles). These plaques and tangles in the brain have come to be characteristic brain changes due to AD.
Symptoms include:
Initial mild forgetfulness
Confusion with names and simple mathematical problems
Forgetfulness to do simple everyday tasks, like brushing their teeth
Problems speaking, understanding, reading and writing
Behavioral and personality changes
Aggressive, anxious or aimless behavior

Information from the National Mental Health Association.