IPA Bulletin
Recent Advances - Volume 18, Number 2
John O'Brien and Bob Barber
The suggestion that the effects of Parkinson’s disease are not confined to the brain is provided by Goldstein et al. (Annals of
Internal Medicine 2000; 133:338-47) who, using Positron Emission Tomography, found that patients with Parkinson’s disease had
decreased numbers of noradrenaline producing nerve endings innervating the heart. All of those with sympathetic neurocirculatory failure had
evidence of cardiac sympathetic loss. The authors conclude that loss of catecholamine innovation in Parkinson’s disease occurs not only in the
nigrostriatal system in the brain has also in the sympathetic nervous system in the heart. Findings were not related to drug treatment or
duration or severity of disease and, interestingly, sympathetic nerve terminals were normal in a comparison group of patients with multi-system
atrophy.
Parkinson’s disease, environmental factors have long been suspected following the description of post encephalitic Parkinsonism and also Parkinsonian symptoms after
damage
to the nigrostriatal system caused by the toxin MTPT. A report by Betarbet et al. (Nature and Neuroscience 3: 1301-1306) found that chronic administration of the pesticide rotenone caused selective nigros-triatal dopaminergic degeneration associated with hypokinesia and
rigidity in rats. Unlike MTPT, which targets dopaminergic neurons because of its affinity for the dopamine transporter, rotenone crosses all cell membranes and should therefore affect all cells. Why the nigrostriatal system appears particularly vulnerable is therefore unclear, although one possible answer is the sensitivity of these cells to oxidative
stress caused by free radicals. The significance of this and possibly other toxins causing Parkinson’s disease in humans remains unknown.
How often do terminally ill patients think about euthanasia, how stable are the thoughts and
what factors influence them?These are some of the questions Emanuel and colleagues
examined in their large prospective study of nearly 1,000 terminally ill patients (JAMA 2000;284:2460-2468). Of these
patients, around 60% supported euthanasia but with only 10% seriously considering such an act. Factors associated with being more likely to consider euthanasia were the presence of depressive symptoms,significant caregiving needs and pain. Conversely, those who felt
appreciated were less likely to think about euthanasia. Follow-up interviews revealed how attitudes changed with time, as approximately half of the terminally ill patients who had originally considered euthanasia changed their minds, and a similar number now contemplated
euthanasia. Patients with depressive symptoms were more likely to change their minds to consider euthanasia.
Head injuries in young men may be associated with increased risk of dementia in late life according to a study published in Neurology (Plassman et al. 2000;55:1158-66). Following-up
World War II Navy and Marine veterans who were hospitalised during military service with either a nonpenetrating head injury or another unrelated disorder, the researchers found both moderate head injury and severe head injury were associated with increased risk of Alzheimer’s disease (AD) and dementia in general. The results for mild head injury
were less conclusive, and there was a trend toward a stronger association between AD and head injury in men with apolipoprotein 4 alleles. However, as the authors acknowledge, possible confounding factors could be influencing the findings.
The controversy over the effect of estrogens in preventing cognitive decline continues. Despite some recent negative therapeutic trials, Yaffe et al. (Lancet 2000; 356:708-712) found evidence of a protective effect of high non-protein bound (therefore bio available)
estradiol at baseline and subsequent cognitive function six years later in 425 women. No such effect was found for testosterone. The authors conclude that their findings support the hypothesis that higher concentrations of endogenous estrogens help prevent cognitive decline.
Hot on the trail of two phase III trials (see previous IPA Bulletin), a further RCT using galantamine (24 or 32mg/day for 6 months) in mild to moderate AD has been published
(Wilcock et al. BMJ 321:1445-1449). Over 650 patients from 86 outpatient clinics in Europe and Canada were recruited, with 80% completing the study. Treatment with galantamine was more effective than placebo in all major outcome measures: cognitive function (using ADAS-Cog), overall change (using CIBIC-plus) and in the higher dose activities of
daily living (using the disability assessment for dementia scale). Apolipoprotein E genotype had no effect on outcome. Consistent with previous publications, the authors concluded galantamine was both effective and safe.
Drs. John O'Brien and Bob Barber are the Research
Editors of the IPA Bulletin. They welcome readers' comments via
e-mail (J.T.O'Brien@ncl.ac.uk) or
fax (+44 191 219 5040). John O’Brien
also is Deputy Editor of the IPA Bulletin.
