Wednesday, May 02, 2007

Reversing Alzheimer's?

The memories destroyed by Alzheimer's disease and other types of dementia could be restored by therapy, research has suggested. Experiments on mice have indicated that long-term memories that appeared to have been lost to degenerative brain diseases can be recovered when the animals are given a promising form of treatment. The research raises the prospect that treatments for Alzheimer's and similar conditions might eventually not only stop patients' mental decline, but reverse damage that has already taken place. It had generally been thought that memory loss caused by dementia was permanent, and that the best that could be hoped for would be drugs and therapies that prevented any further deterioration.

The study, led by Li-Huei Tsai of the Massachusetts Institute of Technology, shows that these memories may not have been erased completely. Instead, damage to the brain may be interfering with Alzheimer's patients' ability to retrieve and use them. "The memories are still there, but they are rendered inaccessible by neural degeneration," Dr Tsai said. "This recovery of long-term memory was really the most remarkable finding. It suggests that memories are not really erased in such disorders as Alzheimer's, but that they are rendered inaccessible and can be recovered."

The research, using mice genetically engineered to suffer a neurodegenerative disease similar to Alzheimer's, also raises hope that two approaches to treatment might be effective. Dr Tsai's team found that enriching the environment of the mice, with treadmills for exercise and colourful toys of many different textures, significantly improved learning and memory, and appeared to build new connections between nerve cells in the brain. This accords with evidence from humans that exercise and mental stimulation, such as learning languages or doing crosswords or Su Doku puzzles, appear to have a protective effect.

Similar results were also achieved by giving the mice a drug known as an HDAC inhibitor, which promotes nerve cell growth. Much more work is needed before this can be tested in people, but scientists said that it was a promising lead. The researchers determined that both treatments can revive lost memories by comparing mice before and after a gene was activated to cause neurological decline. The mice were first conditioned to fear entering a chamber, by giving them a mild electric shock whenever they did so. The animals also learned to find a submerged platform in murky water.

When a gene called p25 was activated, the mice developed symptoms like those of Alzheimer's disease, and forgot both that they were afraid of the electric-shock chamber and the ability to find the platform. After receiving the environmental enrichment or the drug therapy, the mice recovered these lost memories.


Booze is good for your brain too

We have long known that alcohol is good for your heart but it can also prevent dementia! Is alcohol the long awaited cure for Alzheimer's? Not really but it seems to be at least as good as anything else. There is a literature review on the topic below. A J-shaped relationship means that you need to get the dose right to get a good result. Moderation is the key! In addition to the review below, see here for one of the key research papers in the field


There is a clear J-shaped relationship between alcohol consumption and the risk of cardiovascular disease which has been extended to a reduced risk of certain cancers (Boffetta and Garfinkel 1990, Marmot and Brunner 1991, Thun et al. 1997). Over the last five years, evidence has accumulated which suggests that this J-shaped relationship could also be extended to a reduced risk of cognitive dysfunction. Cognitive function is defined as the intellectual or mental processes by which knowledge is acquired, including perception, reasoning, acts of creativity, problem-solving and possible intuition.

Cognitive dysfunction or impairment is associated with increased disability and an increased need for institutionalised care, especially in an ageing population. While cardiovascular disease accounted for 40% of all Australian deaths in 2000 and cancer accounted for 25-30%, 6% of the Australian population aged 65 years and over were diagnosed with dementia. Dementia is a form of cognitive dysfunction whereby an individual loses the ability to think, remember and reason due to physical changes in the brain. Given the anticipated ageing of the Australian population over the next 50 years, for example, the median age of Australia's population is projected to increase from 35.4 years in 2000 to 46.5 years in 2050 (ABS 2003), research on risk factors for these diseases is a national priority.

Relationship between alcohol and cognitive function

Prior to a study by Zuccala et al. (2001), there was conflicting evidence on the relationship between alcohol consumption and cognitive function (Cervilla et al., 2000; Dent et al., 1997; Dufouil et al., 1997; Elias et al., 1999; Harwood et al., 1999; Hendrie et al., 1996; Leibovici et al., 1999; Teri et al., 1990). Zuccala et al. (2001) analyzed the association between alcohol consumption and cognitive impairment in 15,807 hospitalized older patients who were enrolled in an Italian multicentre pharmacoepidemiology survey. The probability of cognitive impairment was reduced among male patients who reported an average daily alcohol consumption of 1 L or less of wine, as compared with abstainers, but the probability increased among heavier drinkers. Among women, only the lightest-drinking category (<0.5 L) showed a decreased probability of cognitive dysfunction when compared with abstainers, whereas heavier drinking was associated with an increased probability of cognitive impairment. The prevalence of alcohol abuse was similar among participants with cognitive impairment (0.9%) and those with normal cognitive functioning (1%). The results of this study indicated that moderate alcohol consumption, that is, <40 g per day for women and <80 g for men, is associated with reduced probability of cognitive impairment as compared with abstinence, after adjusting for potential confounders. This nonlinear association persisted when cerebrovascular and Alzheimer's disease were considered separately. Such a nonlinear association might explain the conflicting results of previous studies regarding the relationship between alcohol consumption and cognitive functioning.

The observed gender difference in amount of alcohol consumption necessary for improved cognitive function, confirms that observed by Elias et al. in 1999 who showed that `superior' cognitive performance was found with in the range of four to eight drinks per day for men but only two to four drinks per day for women, compared to abstainers.

Subsequent studies have also independently assessed the association between alcohol consumption and cognitive function and have affirmed the observations of Zuccala et al. (2001) but have also provided more detailed data (Ganguli, et al. 2005, Stampfer et al. 2005, McDougall et al. 2006, Reid et al. 2006, Wright et al. 2006). For example, Reid et al. (2006) in a study of 760 US men aged 65 years or older showed that current light to moderate alcohol consumption considered as up to seven drinks per week, compared to abstinence, had better cognitive function. In particular, processing speed, which is the ability to perform tasks requiring rapid visual scanning and mental processing of information, was better even after adjusting for potential confounders such as education and occupation. In addition, the study assessed the effects of cumulative lifetime alcohol consumption on cognitive function and showed that the number of years of light to moderate alcohol consumption was strongly associated with better cognitive function. Results from a small survey study by McDougall et al. (2006) also suggested that men aged 65 years or older who drank moderately had significantly less depression, higher self-reported general health and higher cognitive function, flexibility and verbal memory.

Several studies had shown that the association between alcohol consumption and cognitive function is stronger for women than for men, which may simply reflect a gender difference in cognitive function or perhaps a misclassification of moderate alcohol consumers. Such a gender difference was not, however, observed by in a longitudinal study of 1624 Japanese American men and women aged over 65 years (Bond et al. 2005). Other studies which assessed women specifically, such as the US Nurses' Health Study, suggested that for women aged 71 to 80 years, up to 15g alcohol per day did not impair cognitive function and actually improved it compared to abstinence (Stampfer et al. 2005); the women also had a decreased risk of cognitive impairment of approximately 20%. No significant differences were observed in cognitive performance or risk between beer and wine consumers. Furthermore, a study of women aged 65-80 years, showed that women consuming any alcohol performed better on tests of verbal knowledge, fluency and memory, and figural memory, attention and working memory and motor speed compared to abstainers (P<0.05) (Espeland et al. 2006). After covariate adjustment, mean scores were higher among women reporting ?1 drink/day by 5.7% for verbal knowledge (p<0.001) and by 5.7% for phonemic fluency (p=0.004), compared to abstainers.

Potential mechanisms of action

The beneficial effects of alcohol on the risk of cardiovascular and cerebrovascular diseases, such as heart attacks and strokes, have been partly attributed to changes in lipid and haemostatic or blood flow factors (Rimm et al., 1999). These changes include alcohol-induced increases in the concentration of high density lipoprotein-cholesterol and the thrombolyic proteins tissue type plasminogen activator activity and tissue type plasminogen activator antigen, and alcohol-induced reductions in fibrinogen, and clotting cofactors factor VII and von Willebrand factor. These changes are also associated with atherosclerosis which is the accumulation of atheromatous plaques containing cholesterol and lipids on the innermost layer of the walls of large and medium-sized arteries. As atherosclerosis has been associated with both Alzheimer's disease and vascular dementia, it had been suggested that any beneficial effect of alcohol on atherosclerosis could be expected to benefit these major subtypes of dementia by preserving brain vasculature, consequently resulting in better cognitive function. Wright et al. (2006), however, showed that the appearance of plaque on the carotid artery which carries blood to the brain was not associated with alcohol consumption and alcohol-associated improvements in cognitive function. This suggests then that alcohol may impact cognition through a separate vascular or degenerative pathway. Among older persons without cerebrovascular disease, those who moderately consume alcohol have been shown to have fewer white-matter abnormalities and infarcts on magnetic resonance imaging than abstainers (Mukamal et al. 2001), where pronounced reductions in the risk of both vascular dementia and Alzheimer's disease have been shown among persons consuming one to six standard drinks per week (Mukamal et al. 2003).

Indeed, there is also evidence which suggests that a light to moderate amount of alcohol may stimulate the release of acetylcholine in the hippocampus leading to improved cognitive function such that a light amount of alcohol in normal subjects appears to improve memory for events experienced before consumption where the impairment of memory performance by chronic and heavy alcohol consumption parallels the reduction of acetylcholine neurotransmission (Fadda and Rossetti 1998).


The protective effect of light to moderate alcohol consumption against cognitive dysfunction, including dementia (Simons et al. 2006), has been consistently observed over the past five years. Thus, while excessive alcohol consumption should be avoided, it would appear safe and reasonable to recommend the continuation of light to moderate alcohol consumption in those already imbibing.



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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