Poster Presentution: Drug Studies II

platelet aggregation observed with lower agonists doses was similar pre and post treatment when we used co1 (I pg/ml), Epi (3&M), or AA (OS l.~Mf. However, m the case of ADP (OSp_M) the platelet aggregation was partially inhibited (around 50%) in post treated PRP samples from all patients groups. Conclusion. We have tested in a preliminary study the “in vwo” platelet antiaggregant effect of distinct anticholin- esterase druga frequently used for AD treatment. These drugs did not significantly affect platelet aggregation under high and low stimulation of platelet aggregation with collagen, epinephrine and arachidonic acid. This is in agreement with the absence of haemorhagic complications associated with these drugs. However, all of them seem to inhibit platelet aggregation at low ADP doses (0.5 PM), but not at high doses (5 FM).

110921 EVALUATION OF THE EFFECTS OF THERAPY IN INDIVIDUAL PATIENTS WITH ALZHEIMER’S DISEASE; LIMITATIONS AND OPPORTUNITIES.

Currently cholinesterase inhibitors are being ued for treatment of Alzheimer’s disease on the basis of resulta of large double-blind placebo controlled clinical trials. However, it is difficult to determine the clinically relevant efficacy of this medication for individual patients from the results from this type of clinical trials. With the help of standardised measurements the clinical relevance can be established for individual patients. An extra burden on patients, caregivers and doctors should be avolded. In order to create a widely applicable method which doesn’t require special expertise of the clinician, these measurements should be simple. Changes in cognition as well as behaviour and the ability to perform daily activities should be measured. to get a good impression of the over-all condition of an Alzheimer patient. Using a combination of three clinimetrical scales, one for each of the above domains of functioning, that take less than IS minutes to complete. seems to be efficient. To compensate for mearurement errors from the clmimetrical scaler, both magnitude and pattern ot change should be analyzed for all three the domains of functionmg. Comparison of these data with data from a group of untreated Alzheimer’s patients can gwe an impression of the efficacy of the medication. With the use of goal-attainment scaling, measurements can be individualised even more by paying special attention to rpecific areas of functioning. defined by patient and caregiver as most unportant. This approxh allows for a well informed decision by the clinician and care-giver whether or not to continue treatment. In our poster we present a few specific examples of patients to \how how easily feasible and highly informative the methods described here are.

USE OF AN ACETYLCHOLINESTERASE INHIBITOR IN POST- CABG ENCEPHALOPATHY-A CASE STUDY

Encephalopathy following coronary artery bypass graft (CABG) surgery i\ a common complication of the procedure. Known causes of metabolic and respiratory enceph- alopathy are readily treated with resolution of the mental status changes. However, a large number of encephalopathy cases have no clear-cut etiology. Many theories have been advanced to explain these cases but none have been satisfactory. Treatment of idiopathic cases ia equally frustrating. Assuming that one of the causes is alteration of neurotransmitter function, agents that may help correct this could be useful in correcting the problem. Donepezil, an acetyl cholinerterose inhibitor, has been useful for the treatment of AlLheimer’r disease. Postulating that a simdar neurotranrmitter deficit may be seen in post CABG encephalopathy, these authors did a pilo! study using donepezil in Casey that had no obvious cause. Six patients wth post CABG encephalopathy were placed on doneperil Smgs per day. Of these air patients, two had diabetes meelitus. one type I and one with type 11. One patient had a htstory of alcohol use daily for more than 60 years. None of the patients had focal neurologic deficits. All patxnts were confused. Two patients had active hallucinations, one auditory and one visual. Laboratory values for all these patients were unremarkable with the exception of elevated blood glucose in two patients with know diabete?. All patients returned to normal mental status in four days from the Etart of donepuil in spite of other medications used. Patients with similar findings and no use of doneperll took five to six days to clear. This small case study strongly suggests that acetyl cholinerterase inhibitors, such as donepezil, can help clear mental status in post CABG encephalopathy. The findings here suggest that a larger ttudy should be undertaken.

S239

GALANTAMINE’S CLINICAL BENEFITS ARE NOT OFFSET BY SLEEP DISTURBANCE: A 3-MONTH PLACEBO-CONTROLLED STUDY IN PATIENTS WITH ALZHEIMER’S DISEASE

Kenneth Roc!mvod, Dalhousie Univ. Halifax, NS Canada; Paul Kershaw, CNS Clin Research, Jans~rn Research Fdn, Beerse Belgium

Objectwes: Sleep disturbance can be particularly troublesome for patients with Alrheimer’s disease (AD) and for their carers. This 3.month study was undenaken to assess the safety and efficacy of galantamine in patients with AD. As part of the safety analysis, the effects of galantamine on quality of sleep were assessed. Method: A multicenter, randomized, double-blind, placebo-controlled trial was undertaken in 386 patients with mild-to-moderately severe AD. The galantamine dose was escalated over 3 weeks to 24 @day. This was then continued or increased to 32 mglday in the 4th week, depending on tolerability. At the end of the 4th week patients who could not tolerate 32 mg/day had their dose reduced to 24 mg/day. The final dose was then maintained for a further 2 montha. Activities of daily living (ADL) were assessed using the Disability Assessment for Dementia (DAD), and cognitive function was assessed by the Alzheimer’s Disease Assessment Scale cognitive subscale (ADAS- cog). Global response was evaluated with the Clinician’s Interview-Based Impression of Change plus Caregiver Input (CIBIC-plus). Quality of sleep was assessed with the Pittsburgh Sleep Quality Index (PSQI). Results: At 3 months, galantamine produced significantly better outcomes than placebo on ADAS-cog (drug-placebo difference 1.9 points, p = 0.002) and DAD (drug-placebo difference 4. I points, p = 0.004). Galantamine also produced a better overall clinical response. on CIBIC-plus 0, = 0.003). Overall 75% of patients completed the study (90% of placebo patients and 67% of galantamine patients). Adverse events (mostly gastrointestinal effects) occurred mainly during the dose-escalation phase and were mild-to-moderate. At 3 months, there was no significant difference between galantamine- and placebo-treated patients for mean scores on the PSQI, indicating that galantamine maintains quality of sleep. Conclusion: The cognitive and functional benefits produced by galantamine are not offset by drug-induced sleep disturbance. The absence of adverse effects on patients quality of sleep with galantamine is an important benefit for patients and carers.

piBq DONEPEZIL ITALIAN GLOBAL IMPACT STUDY (DIGIS)

Donepezil is an acetylcholinesterase inhibitor approved in the treatment of mild and moderate AD patients in many countries, including Italy. Past studies on doneperil lasted at mo\t one year and were conducted on selected patient populations. More insight on the dixare course of patients taking donepezil can be gained by studying a large unselected population sample for a period of time representative of the disease duratmn. A multicenter prospective observational study on a cohort of 800 mild or moderate AD outpatients (NINCDS-ADRDA and DSM-IV criteria) is currently being carried out. The participating centers are representative of all Italian geographical and cultural areas. No exclusion criteria other than those reported in the patient Information leaflet have been introduced. All patients, whether still under donepeLi1 treatment or not. will be followed up every 6 months, for 3 years. Cognitlvr (MMSE, Blessed Information-Memory-Concentration), functional (Spontaneous Behavior In- tervwv (SBI ). Blessed Dementia Scale), behavioral (Neuropsychiatric Inventory. SBI) and clinical domainr will be assessed along with economical and emotional $tre\s of the carer The study will also offer the opportunity to highlight less frequent adverse events or those related to a long exposure. The impossibdity to run randomized, placebo-controlled trials on already approved drugs should not prevent further study on how the treatment affects the disease course. To partially make up for the abwncs of a contt-oI group. comparisons were planned with drop-out,. raw data from experiments with antidementu druga. and theoretical decay curve\. ‘The length ot the obaervatiou tune offers the possibility to evaluate the incidence of chnically significant endpoint, such as mstitutionalizatmn. death and reaching AD severe stage or a high mcompetence in the activities of daily living. Moreover the long duration will allow us to reliably measure the slope of change of the selected measure\.