An end to “postcode prescribing” of cholinesterase inhibitors for
patients with Alzheimer’s disease was needed, Professor Gordon Wilcock
(professor of care of the elderly, University of Bristol) indicated recently.
He said that the drugs were “modestly effective” in treating cognitive
impairment and this symptomatic approach to treatment was an important step
forward. However, in many areas there was no NHS funding for the drugs.
Cholinesterase inhibitors were being evaluated by the National Institute for
Clinical Excellence (NICE). “There is so much evidence now that the drugs
can produce some benefit. I hope NICE will assess the evidence objectively and
am cautiously optimistic that the drugs will become more widely available,”
Professor Wilcock said.
Speaking on October 6 at a conference organised by the Royal Society of Medicine,
Professor Wilcock said that 30 to 50 per cent of patients would respond to cholinesterase
inhibitors in a meaningful way, with measurable improvement in cognition which
would be maintained for at least six, and possibly 12, months. The drugs also
had beneficial effects on behaviour and reduced the time that carers had to
spend supervising and helping patients. It was not surprising that some patients
did not respond to the drugs, given the genetic and clinical heterogeneity of
Alzheimer’s disease.
Discussing guidelines for treatment, Professor Wilcock said that the drugs might
be tried in patients with a diagnosis of probable Alzheimer’s disease (mild
to moderate) of more than six months’ duration.
The early response, particularly with respect to side effects, should be assessed
after about two weeks. Upper gastrointestinal effects were the most likely to
occur but did not generally cause a problem. At three months, the patient should
be assessed to see whether treatment had had any effect on cognition, the patient’s
day-to-day life or the carer. After that, it was important to re-evaluate treatment
every six months to see whether improvement was maintained.
Deciding when to stop treatment could be difficult. It should be stopped early
in cases of poor tolerance or poor compliance. It should also be stopped if
there was continued deterioration (at the pre-treatment rate) after three to
six months, or if a patient on maintenance treatment showed accelerating deterioration
(ie, if it appeared that benefit was not being maintained). Another reason for
stopping would be if a drug-free period (of four to six weeks) suggested that
treatment was no longer helping.
Outlining newer approaches to treatment of Alzheimer’s disease, Professor
Wilcock said that researchers were examining the potential for disease modifying
(neuroprotective) approaches to combat the development of amyloid protein and
the formation of neurofibrillary tangles. Strategies included prevention of
cleavage of amyloid precursor protein to produce amyloid protein and immunisation
against formation of amyloid, which was showing promising results in animal
studies.
A number of other therapeutic strategies had also been tested, including the
use of antioxidants, such as vitamin E. Antioxidants had a possible neuroprotective
effect although the evidence was not yet strong enough to recommend their use.
Epidemiological data showed that women taking hormone replacement therapy had
less chance of developing Alzheimer’s disease and that those who did get
the disease did so later than women not taking HRT. However, attempts to treat
Alzheimer’s disease with HRT had not worked, so it appeared that it had
more of a protective effect. There were also epidemiological data showing that
people taking non-steroidal anti-inflammatory drugs had a slower rate of deterioration
in Alzheimer’s disease but, as with HRT, no compelling evidence yet existed
to recommend these drugs for treatment.
Some trials had indicated that Ginkgo biloba might be of benefit. “It is
not sufficiently proven to advise patients to take it, but there is no reason
to say no. In my area, where cholinesterase inhibitors are not funded, if the
patient or carer wants to do something we suggest they could try vitamin E or
ginkgo,” Professor Wilcock said.