Alzheimer-Therapy? Forget It!

5. April 2011
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Causally-effective drugs for the treatment of Alzheimer's disease are not in sight. A diagnosis before the onset of dementia is still quite possible. The big question however is: What to do?

As yet there are only drugs that delay progression of Alzheimer’s disease at best. A cure is not possible and also not in sight. “I do not think we will have solved the puzzle in ten years,” says Professor Dr. Harald Hampel of the Goethe University in Frankfurt. As with other chronic diseases, the hope, therefore, focuses more on prevention through non-pharmacological measures as well as by drugs. Targeted prevention requires identifying the disease process as early as possible. Thanks to many advances in research, early diagnosis is today possible. The focus is on biomarkers and imaging techniques.
Yet it’s not only high-tech medicine which plays an important role in early diagnosis.

According to psychiatrist and professor Hermann-Josef Gertz of the University of Leipzig, and Alexander Kurz of the University of Munich, Alzheimer’s disease (AD) can be subdivided into an asymptomatic stage and into two further symptomatic stages: a clinical stage of mild cognitive impairment (MCI or “mild cognitive impairment”) and the stage of dementia.

Dementia diagnosis in fluids, colourful pictures and special tests

The clinical diagnostics for dementia (third stage) are already established. They are based on the detection of memory disorders plus at least one other cognitive disorder, such as aphasia . Neuropsychological tests according to CERAD (“Consortium to Establish a Registry of Alzheimer’s Disease“) enable quantifiable statements of assessment of these cognitive deficits to be made. Associated behavioral problems are to be assessed, for example, by using the Neuropsychiatric Inventory (NPI). Characteristic findings are: in MRI scans an atrophy of the medial temporal lobe; increased total τ-or phospho-τ concentration with decreased β-amyloid concentration in cerebrospinal fluids; and in cerebral metabolic disorders – by using special PET ligands – deposits of β -amyloid in the cerebral cortex.

An increased risk of dementia can also be detected

A relatively-certain early diagnosis is, as psychiatrists in a recent review report, already possible today in the MCI-stage, which is before there is even talk of the onset of dementia and the indication for treatment using anti-dementia drugs such as donepezil, rivastigmine, galantamine or memantine.
Early diagnosis is possible with evidence of memory impairment, from tests such as “Free-and-Cued Selective Reminding Test-Recall” which has, according to Gertz and Kurz, a sensitivity of almost 80 percent and specificity near 90 percent. An MRI scan may also be helpful in the LCI-stage in the detection of temporal lobe atrophy. Possibly revelatory might also be the detection in cerebrospinal fluids of increased total-τ or phospho-τ concentration and a decreased β-amyloid concentration. Much more complicated, and by contrast not suitable for routine diagnosis, are PET scans, whether they involve detection of impaired glucose metabolism in certain brain regions, or in-vivo imaging of amyloid using specific PET ligands (such as Florbetaben produced by Bayer in Leverkusen).

Something worth noting: A declaration of becoming forgetful

As especially fascinating as imaging techniques in early diagnosis may be, the mere declaration by a patient about becoming more forgetful should surely prick up one’s ears. Indeed, among those patients who still don’t have an objectivised MCI, but themselves have concerns with their forgetfulness, over years there is a statistical tendency to develop dementia at an above-average frequency. This was revealed by a German longitudinal study by Professor Frank Jessen (University of Bonn) and his colleagues, which was published nearly a year ago (“Archives of General Psychiatry“).

Early Diagnosis: A blessing indeed?

A key issue currently revolves around what benefit an early diagnosis serves at all and whether it might not even harm. For patients and relatives, a very serious diagnosis, according to Gertz and Kurz, is still currently “subject to some uncertainty.” The positive results of early diagnosis with biomarkers and imaging techniques have been achieved in studies under “experimental” conditions. In everyday practice things looks perhaps more limited. On the other hand, an early diagnosis enables the timely discussion of a future with AD and the “development of coping strategies”, plus “changed life planning and adaptation to the disease”.

The main problem rather is, that no causally-effective therapy exists that bring about healing. What has existed until now is a variety of non-pharmacological and pharmacological approaches. Apart from steps to be taken toward cognitive stimulation and mental training, what has long been discussed and recommended is a healthy lifestyle (such as a calorie-reduced diet and physical activity). Scientists also have an increasingly good basis for this reasoning; More and more observational studies show an association between cognitive performance drops on the one hand and metabolic syndrome, diabetic metabolic situation and obesity on the other hand. There are also observational studies that suggest that intervention in insulin resistance and obesity, for instance light physical activity such as walking, perhaps slow down the degradation of cognitive performance.

At least: many approaches

Pharmacological approaches in early intervention have of course long been discussed, such as using agents active against mitochondrial dysfunction and others, such as bilobalide and querceptin, that are involved in the stimulation of neurogenesis and synaptogenesis (“Journal of Alzheimer’s Disease“). Neuroprotective effects against memory disorders and Alzheimer’s disease have been even attributed to caffeine, as was presented last year in a supplement – funded by the Spanish coffee industry – of the renowned “Journal of Alzheimer’s Disease“. All of these are nonetheless still mainly research, in which there have also been setbacks. For instance a “ray of hope” substance (as Dimebon is purported to be) that improves mitochondrial function did not outperform a placebo in a Phase III trial with 600 patients, as Pfizer and its partner Medivation were forced to report last year.

Sobering realisation: a lot of research, little evidence

No particularly good news was announced most notably in April 2010 by a U.S. expert committee, which had analysed the available scientific literature on behalf of the U.S. Department of Health. The main conclusion of the scientists was that so far no non-pharmacological and pharmacological measure is available that can prevent Alzheimer’s disease. According to the present data, there is no clear proof for any measures, whether they be physical activity or fish oil, stated Dr. Martha Daviglus (Northwestern University, Chicago), head of the panel. Most studies showed only a correlation but no causal relationship. And that is, in the rigorous field of science, too little.

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3 comments:

Dr Paul Wieland
Dr Paul Wieland

What a shame that cannabis is illegal in most places of this world. Here we have a plant with proven health benefit including strong evidence of slowing down the progress of Alzheimers, and we can’t use it.

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Dr. Nathan Daley
Dr. Nathan Daley

“Most studies showed only a correlation but no causal relationship. And that is, in the rigorous field of science, too little.”

If the rigorous standand of science is the mega-expensive RCT, then is it no surprise that non-pharmaceutical methods lack “clear proof” of efficacy? This should not lead to inaction, but to innovation and the application of safe and possibly effective approaches in the clinic.

We are doing just that, and I remain optimistic that AD can be prevented and even reversed today. See our AD program at http://www.LeonardiInstitute.com for more details. We are accumulating evidence and will publish at 1 year intervals.

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Rudy Faelens
Rudy Faelens

Indeed,

So let’s focus more on a non-pharmacological approach on the disease.
With the savings on non-precription of ACCH inhibitors in long term care – where medication shows absence of any evidence – we have enough money to pay a nurse specialised in Alzheimer. With proven effect on quality of life

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