Stand by for a battle-royal over Alzheimer's disease (AD)-to take place in the British High Courts of Justice, no less. Shortly, in a unique court case, NICE (National Institute for Clinical Excellence), the UK's National Health Service drugs watchdog, will be challenged to defend its decision not to fund Alzheimer's drugs intended for use in the early stages of the disease.

Ranged on the prosecution benches will be two big guns of the pharmaceutical industry, Pfizer and its marketing arm Eisai, aided and abetted by the Alzheimer's Society, a vociferous patient support group that equally loudly proclaims itself to have no ties with any drug manufacturers.

What's all the fuss about? Are the Alzheimer's drugs any good at all, and are there any alternatives? And what causes the disease in the first place?

Dementia and Alzheimer's
From near-obscurity only a generation ago, Alzheimer's disease is now probably, after cancer, the most feared disease of old age. Alzheimer's has been chillingly described as an affliction whose victims suffer the loss of qualities that define human existence.

Once considered a rare disorder, it is now known to be the most common type of senile dementia, defined as physical damage to the brain in old age that results in major changes to reasoning, memory, personality and behaviour. Until recently, the only way to distinguish Alzheimer's from other types of dementia was by post-mortem examination of the brain. A typical AD brain is found to be partly atrophied, with the brain cells clumped together in what are called 'neurofibrillary tangles' or 'plaques'.

The second major type of dementia is vascular dementia, where the interruption of the brain's blood supply, usually due to 'mini-strokes', causes brain cells to die. These two main types of dementia can now sometimes be distinguished from each other by brain scans using either magnetic resonance imaging (MRI) or positron-emission tomography (PET).

Senile dementia is not as inevitable as many people might imagine: between 25 and 50 per cent of individuals over 85 are spared it. Nevertheless, dementia is on the increase, so the drug companies claim, because of the simple fact that we're all living longer. It is believed to be incurable.

Big Pharma's offerings
Any prolonged chronic illness that is only ended by death is, of course, meat and drink to the pharmaceutical industry. And yet, perhaps surprisingly, there are relatively few drug treat-ments available for Alzheimer's. First on the market was tacrine (marketed as Cognex) in 1993. Like virtually all of its successors, tacrine is a so-called cholinesterase inhibitor, which acts by artificially maintaining levels of acetyl-choline in the brain. This important brain chemical is known to be reduced by as much as 90 per cent in AD sufferers; it's also believed to be important for memory, so finding a drug that can preserve the chemical in the brain makes sense.

In fact, the theory is fine-the trouble is the side-effects. After just a decade on the market, tacrine began to be no longer actively marketed after reports of severe liver toxicity. As much as 60 per cent of patients found the drug's side-effects to be intolerable at high doses. The final nail in tacrine's coffin was that, after all this, it really doesn't work (JAMA, 1998; 280: 1777-82).