Sarah Eagger

Further analysis of the cognitive effects of tetrahydroaminoacridine (THA) in Alzheimer's disease: assessment of attentional and mnemonic function using CANTAB

Results of a placebo controlled cross-over trial (N=89) of the anticholinesterase drug THA as a treatment for dementia of the Alzheimers type (DAT) are reported, with reference to previous trials of the drug and the cholinergic hypothesis of aging and dementia. Using computerised tests sensitive to specific aspects of memory and attention, evidence is found for improvements in attentional function rather than memory, in patients with mild to moderate DAT. Although these improvements were significant, they were small and restricted to certain tests of attentional function. Nevertheless, they add to the growing body of evidence that the cholinergic system is involved in the control of attentional processes. The results will be relevant to future investigations into the therapeutic effects of enhancement of the cholinergic system in DAT sufferers.

Platelet and erythrocyte membrane changes in Alzheimer's disease

Previous reports have suggested that the physical properties of cell membranes and calcium homeostasis in both the central and peripheral nervous system are changed in Alzheimers disease (AD). This study has examined the biophysical properties of erythrocyte and platelet membranes by measuring the fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene (DPH) and possible related changes in lipid peroxidation. In addition, we have studied calcium homeostasis by measuring thrombin-stimulated changes in intraplatelet free calcium and Ca2(+)-ATPase activity in AD and healthy age and sex-matched controls. Our results show that there was no significant difference in the fluorescence anisotropy of DPH in erythrocyte membranes isolated from the three groups. There was also no significant difference in lipid peroxidation levels in erythrocytes and plasma of AD patients compared to controls. However, there was a significant reduction in the fluorescence anisotropy of DPH in platelet membranes from AD patients, compared with healthy controls. Recent evident suggests that the increase in platelet membrane fluidity results from alterations in internal membranes. We measured the specific activities of enzyme markers associated with intracellular and plasma membranes in platelets from AD patients and healthy controls. There was a significant reduction in the specific activity of antimycin A-insensitive NADH-cytochrome-c reductase (a specific marker for smooth endoplasmic reticulum (SER)), in AD patients compared to controls, but no change in the specific activity of bis(p-nitrophenyl)phosphate phosphodiesterase (a specific marker for plasma membrane). We have also shown that SER mediated [Ca2+] homeostasis is possibly impaired in AD platelets, i.e., the percentage of thrombin-stimulated increase in intraplatelet [Ca2+] above basal levels was significantly higher in AD compared to matched controls and there were significant reductions in the specific activities of Ca2+/Mg2(+)-ATPase and Ca2(+)-ATPase (but not Mg2(+)-ATPase) in AD platelets. Finally electron microscopic analysis of platelets showed that there was a significant increase in the incidence of abnormal membranes in AD patients compared to controls. The ultrastructural abnormalities seem to consist of proliferation of a system of trabeculated cisternae bounded by SER. These results suggest that both SER structure and function might be defected in AD platelets, which could explain the fluidity changes observed here.

Spirituality and secularity: professional boundaries in psychiatry

Spirituality is assuming increasing importance in clinical practice and in research in psychiatry. This increasing salience of spirituality raises important questions about the boundaries of good professional practice. Answers to these questions require not only careful attention to defining and understanding the nature of spirituality, but also closer attention to the nature of concepts of secularity and self than psychiatry has usually given. Far from being “neutral ground,” secularity is inherently biased against concepts of transcendence. Our secular age is preoccupied with a form of immanence that emphasises interiority, autonomy and reason, but this preoccupation has paradoxically been associated with an explosion of interest in the transcendent in new, often non-religious and non-traditional forms. This context, as well as the increasing evidence base for spiritual and religious coping as important ways of dealing with mental stress and mental disorder, requires that psychiatry gives more careful attention to the ways in which people find meaning in spirituality and religion. This in turn requires that more clinical attention be routinely given to spiritual history taking and the incorporation of spiritual considerations in treatment planning.

Tacrine in Alzheimer's disease

Tacrine (tetrahydroaminoacridine) plus lecithin were studied in a randomized, double-blind, placebo-controlled, crossover study. Patients with probable Alzheimer’s disease were selected from those attending the memory clinic at a psychiatric hospital. Of the 89 patients included, 24 were withdrawn, 19 because of side-effects, 4 with other illnesses, and 1 for non-compliance. The active treatment was the maximum tolerated dose of tacrine up to 150 mg daily plus 10.8 g lecithin daily. Patients were randomly assigned to active or placebo treatment and crossed over after 13 weeks’ treatment and 4 weeks’ washout to the other treatment. The main outcome measures were the rninimental state examination (MMSE), the abbreviated mental test score (AMTS), and the caregiver’s rating of the activities of daily living scale. Analysis for the 65 patients who completed the trial showed a significant beneficial effect of tacrine over placebo in the MMSE score (p<O.OOOl; 95% confidence interval for group change on tacrine over that on placebo 1.67-3.71); 29 (45%) patients showed an improvement of 3 or more points on tacrine compared with 7 (1 1%) during placebo. The findings with the AMTS were similar (p = 0.0001); 95% CI 0.36-1.38) but the ADL score showed no significant treatment effect. There was substantial variation in response among the subjects. Dosedependent rises in serum liver enzymes were common but reversible. Tacrine produced an improvement in key outcome measures roughly equivalent to the deterioration which might have occurred over 6-12 months. The clinical relevance of the findings is a matter for individual judgment.

Spirituality and the Practice of Healthcare

![][1] Have the taboos around spirituality begun to fall away? Certainly there appears to be a lot of interest in this subject at the moment. For example, the Royal College of Psychiatrists has a special interest group on spirituality and psychiatry ([www.rcpsych.ac.uk/spirit][2]),

Spirituality and the Practice of Healthcare: Robinson, S., Kendrick, K., Brown A. Basingstoke: Palgrave

![][1] Have the taboos around spirituality begun to fall away? Certainly there appears to be a lot of interest in this subject at the moment. For example, the Royal College of Psychiatrists has a special interest group on spirituality and psychiatry ([www.rcpsych.ac.uk/spirit][2]),