Wednesday, August 29, 2007


Whether there were any double-blind procedures is unclear. In any case it appears to be the usual epidemiological nonsense of assuming causation from correlation. Once again that wicked social class is ignored, for instance. Poor people are much less compliant with drug regimes (particularly nasty ones like statins) and may seek medical help less so may be given less statins -- and poor people have worse health generally (and some might have more scrambled brains to begin with) so might have more brain tangles. So is this just documenting another correlate of poverty? See also more cautions here. Journal abstract follows media report below

Taking statins may help to prevent Alzheimer's disease, a study has directly suggested for the first time. Researchers in the US claim to have uncovered clear evidence that the cholesterol-lowering drugs - taken daily by about three million people in Britain - could ward off the illness. The large-scale study, conducted at Boston University from 2002, found that the drugs may cut the risk of getting Alzheimer's by as much as 79 per cent, even in people thought to be genetically susceptible to the disease. The lead author, Gail Li, said the study was the first to compare the brains of people who had received statins with those who had not.

Previous research has indicated that Alzheimer's may be caused by poor blood flow and vascular changes in the brain, which statins may help to prevent. Dr Li, from the University of Washington School of Medicine in Seattle, and her colleagues examined the brains of 110 Americans who had died aged between 65 and 79, and had donated their organs for research.

The two changes in the brain considered the hallmarks of Alzheimer's are known as brain "plaques" and "tangles". These are protein deposits that appear to spread in the brain, although the cause of Alzheimer's is not yet fully understood. The researchers found significantly fewer tangles in the brains of people who had taken statins than those who had not, even allowing for variables such as age, gender and past health.

Eric Larson, a co-author of the study, said: "These results are exciting, novel and have important implications for prevention strategies." He said further studies were needed to confirm the findings but praised the researchers' reliance on automated records and postmortem examinations of people with and without dementia. Dr Li said: "Statins are probably more likely to help prevent the disease in certain kinds of people than others. Some day we may be able to know more precisely which individuals will benefit from which types of statins."

In June, the National Institute for Health and Clinical Excellence (NICE) published draft guidance suggesting millions of people should be assessed to find out how many more would benefit from statins, which are estimated to prevent up to 7,000 deaths a year from heart attacks and strokes. Information collected routinely by GPs should be used to identify those most at risk of developing cardio-vascular disease, it said. Adults who have a 20 per cent or greater risk of developing heart disease over the next decade should be offered statins, it added. Such a move would double the number of people prescribed the drug to about six million. Final guidance from NICE is expected in January.

Other studies suggest a downside to statins. They are known to interact with other drugs and can have side-effects, including abdominal pain, diarrhoea and nausea. In July researchers in Massachusetts found that people who took statins had a slightly increased risk of cancer. Statins reduce levels of low-density lipoprotein, an enzyme involved in the transportation of "bad" cholesterol.

There are currently 700,000 people with dementia in Britain, of whom about two thirds have Alzheimer's.


Statin therapy is associated with reduced neuropathologic changes of Alzheimer disease

By G. Li et al.

Background: Treatment with 3-hydroxy-3-methylglutaryl-coenzyme-A reductase inhibitors ("statins") has been associated in some epidemiologic studies with reduced risk of Alzheimer disease (AD). However, direct evidence of statin effects on neuropathologic markers of AD is lacking. We investigated whether antecedent statin exposure is associated with neuritic plaque (NP) or neurofibrillary tangle (NFT) burden in a population-based sample of human subjects.

Methods: Brain autopsies were performed on 110 subjects, ages 65 to 79 years, who were cognitively normal at enrollment into the Adult Changes in Thought Study. Neuropathologic findings were compared between statin users with ~ prescriptions of ~ 15 pills of simvastatin, pravastatin, lovastatin, or atorvastatin vs nonusers, based on pharmacy dispensing records.

Results: After controlling for age at death, gender, cognitive function at study entry, brain weight, and presence of cerebral microvascular lesions, the odds ratio (OR) for each unit increase in Braak NFT stage in statin users vs nonusers was 0.44 (95% CI: 0.20 to 0.95). The OR for each unit increase in Consortium to Establish a Registry for Alzheimer's Disease (CERAD) staging of NPs did not deviate significantly from unity (OR 0.69; 95% CI: 0.32 to 1.52). However, the risk for typical AD pathology (Braak stage ~ IV and CERAD rating ~moderate) was reduced in statin users (OR 0.20; 95% CI: 0.05 to 0.86).

Conclusions: These findings demonstrate an association between antecedent statin use and neurofibrillary tangle burden at autopsy. Additional study is needed to examine whether statin use may be causally related to decreased development of Alzheimer disease-related neuropathologic changes.

NEUROLOGY 2007;69:878-885

Autism progress

Within the next year a new study is expected to identify many of the genes that underlie autism for the first time. At the same time, two new theories are challenging established thinking about autism genetics in ways that could ultimately transform diagnosis and treatment. "The medics tell me we are at a tipping point," said Dame Stephanie Shirley, the millionaire computer entrepreneur and philanthropist, who is the chairman of the research charity Autism Speaks and the mother of an autistic son.

That genetics are the chief cause of autism has been known for three decades. It was in 1977 that Professor Michael Rutter, of the Institute of Psychiatry at King's College London, published a twin study that transformed the understanding of its origins. Twin studies are one of the mainstays of genetics. Because identical twins share all of their genes while fraternal twins share only half, and both share broadly similar environments, comparisons can tease out the relative contributions of nature and nurture. Professor Rutter found that if an identical twin was autistic, it was highly likely that the other twin was autistic too. Fraternal twins, however, were no more likely to share the diagnosis than ordinary siblings. This made it certain that genes played a large role and it is now thought that autism is among the most heritable of all psychiatric disorders. Genetics account for most of the variance and, although environmental factors matter too, they are less important.

The condition, however, has remained a genetic paradox. For all the certainty that genes are heavily involved, it has proved impossible to discover which ones are guilty. In the 30 years since Professor Rutter's study, hundreds of genetic mutations that affect health have been found. Most are single-gene disorders, where inheriting a rogue gene invariably means developing a disease such as Huntington's, which affects the central nervous system. Most of the others have involved very high risks: women with abnormal variants of the BRCA1 gene, for example, have an 80 per cent risk of developing breast cancer.

Autism does not work like that: the search for genes with such large effects has failed. It might be influenced by dozens of genes, each of which raises the risk by amounts too small to have been detected. Or it could be the result of spontaneous mutations instead of more easily tracked defects that are passed from generation to generation. Science does not yet know. [Or it could be that there is no such thing -- merly a number of different disorders with one ort two common symptoms]

The scientific success story of 2007 has been the coming of age of a new method of gene-hunting that can find the sort of genes with weak effects that are thought to influence autism. These genome-wide association studies compare the DNA of thousands of people who have a disease with healthy controls, using tools called "gene chips" to screen the entire human genome for hundreds of thousands of tiny genetic variations that differ between the two groups. In recent months, the technique has revealed scores of genes that subtly influence common conditions such as diabetes, heart disease, breast cancer and multiple sclerosis, often raising the risk by as little as 10 per cent.

Autism is the next target. The Autism Genome Project (AGP), an international consortium that studies more than 1,000 families with at least two autistic members, is about to apply the tool to its database. "We have been waiting ten years for the technology to do this," said Anthony Monaco, of the University of Oxford, one of the project's leaders. "We were never likely to understand until we were able to screen very large numbers. The probability has always been that autism is highly genetic, but highly heterogeneous - that lots of different genes are involved. We now have a great chance of picking them up."

The AGP's genome-wide association study is a classic example of win-win science. Even if it draws a blank, it will still shed new light on the genetic origins of the condition. No results would mean one of two things. It could be that the effects of the genes responsible are even tinier than suspected and bigger samples are needed. Or it could be that a radical new theory of autism genetics is correct.

Professor Michael Wigler, of Cold Spring Harbour Laboratory in New York state, believes that autism might be the result of single genes with big effects after all. These mutations, however, are not quite the same as the inherited ones that cause diseases such as Huntington's. According to his model, most cases of autism are caused by random, spontaneous mutations in the sperm or eggs of parents that are passed on to individual children. Most of these then develop the condition but some, particularly girls, do not. They are somehow resistant and, although they carry a potentially harmful mutation, they do not suffer its consequences.

This may explain why autism is an overwhelmingly male disorder, four times more common among boys than girls. It fits with data showing that the children of older parents are at higher risk: sporadic mutations of this sort increase with age. It also points towards an intriguing explanation for the existence of high-risk families with more than one autistic child. Professor Wigler's research suggests that in these families, a mutation first occurred in one of the parents, usually the mother. While she was immune, probably because of her gender, her sons were not so lucky: half of them would be autistic, depending on whether they inherited the rogue gene. "Sporadic autism is the more common form of the disease and even the inherited form might derive from a mutation that occurred in a parent or grandparent," the professor said.

If mutations of this sort are responsible, they would not show up in the AGP: they are new and unique to individuals and families, so will not surface from large comparisons of DNA. "That is one of the exciting things about our work," Professor Monaco said. "If we find genes, it is interesting and if we don't find genes, it is interesting too."

What Professor Wigler's theory does not account for is another aspect of new thinking about autism: that it may not be a single disorder. For autism to be diagnosed, children must meet three criteria: they must show social impairment, communication difficulties and nonsocial problems such as repetitive and restricted behaviour. Yet there is an emerging consensus that these traits do not always go together and that there are people who meet the criteria for one or two characteristics but who do not receive any diagnosis. Autism, in short, may be the confluence of three separate developmental conditions. Only when they occur together is the result devastating.

Research by Angelica Ronald, Francesca Happe and Robert Plomin, of the Institute of Psychiatry, has suggested that each of these three problems is influenced by different sets of genes. The twin studies have shown that while each trait is highly heritable, they do not often overlap. "The label autism is something that was applied to a set of behaviours that were first described in the 1940s," said Dr Ronald, who is funded by Autism Speaks. "It's not necessarily a label for a clear biological entity and in research it may be a misnomer to assume it's one thing."

This has important implications for gene-hunting. It could be that genes have not been found because scientists have been treating autism as a whole. If different genes affect the communication and social elements of the disorder, finding them might involve looking at people who are not autistic, but who have mild versions of one of the problems. "We need to tackle whether we should look at autism as a single phenomenon, or whether it would be better to look, for example, just at autistic social problems," Dr Ronald said. Such an approach would also be valuable by shedding immediate light on what any genes that are found actually do.

Dr Ronald added: "If we split up the symptoms, we can know that these genes are going to be involved in social problems and those ones in nonsocial problems. That is obviously going to be valuable when we look towards diagnosis and treatment." An understanding of which genes are involved in which parts of autism should help doctors to spot the condition earlier. It would also prepare parents for the way their child is likely to develop and it could help with the design of therapies.

Dame Stephanie is excited by the pace of change. "It is quite possible that in five to ten years, we will have a real understanding of this disorder," she said. "That's a timescale that means today's children may be helped."



Just some problems with the "Obesity" war:

1). It tries to impose behavior change on everybody -- when most of those targeted are not obese and hence have no reason to change their behaviour. It is a form of punishing the innocent and the guilty alike. (It is also typical of Leftist thinking: Scorning the individual and capable of dealing with large groups only).

2). The longevity research all leads to the conclusion that it is people of MIDDLING weight who live longest -- not slim people. So the "epidemic" of obesity is in fact largely an "epidemic" of living longer.

3). It is total calorie intake that makes you fat -- not where you get your calories. Policies that attack only the source of the calories (e.g. "junk food") without addressing total calorie intake are hence pissing into the wind. People involuntarily deprived of their preferred calorie intake from one source are highly likely to seek and find their calories elsewhere.

4). So-called junk food is perfectly nutritious. A big Mac meal comprises meat, bread, salad and potatoes -- which is a mainstream Western diet. If that is bad then we are all in big trouble.

5). Food warriors demonize salt and fat. But we need a daily salt intake to counter salt-loss through perspiration and the research shows that people on salt-restricted diets die SOONER. And Eskimos eat huge amounts of fat with no apparent ill-effects. And the average home-cooked roast dinner has LOTS of fat. Will we ban roast dinners?

6). The foods restricted are often no more calorific than those permitted -- such as milk and fruit-juice drinks.

7). Tendency to weight is mostly genetic and is therefore not readily susceptible to voluntary behaviour change.

8). And when are we going to ban cheese? Cheese is a concentrated calorie bomb and has lots of that wicked animal fat in it too. Wouldn't we all be better off without it? And what about butter and margarine? They are just about pure fat. Surely they should be treated as contraband in kids' lunchboxes! [/sarcasm].

Trans fats:

For one summary of the weak science behind the "trans-fat" hysteria, see here. Trans fats have only a temporary effect on blood chemistry and the evidence of lasting harm from them is dubious. By taking extreme groups in trans fats intake, some weak association with coronary heart disease has at times been shown in some sub-populations but extreme group studies are inherently at risk of confounding with other factors and are intrinsically of little interest to the average person.


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