As heavy metal ions may be implicated in the formation of senile plaques in Alzheimer-afflicted brains, treatment with clioquinol was tested in 20 patients with Alzheimer’s disease. Clioquinol is a chelator that crosses the blood-brain barrier and has greater affinity for zinc and copper ions than for calcium and magnesium ions. Treatment was given for 21 days at doses of 20 mg/day to 10 patients and 80 mg/day to another 10 patients. The study was blind to the dosages but included no controls. Cerebrospinal fluid (CSF) investigations revealed a significant increase at day 7 and a decrease at day 21 in Tau protein and growth-associated protein (GAP43). These proteins are increased in Alzheimer’s disease and considered as rather stable markers. The initial increase may indicate a temporary cytotoxicity to the brain and/or an increased release into the CSF from stores in the tissue, possibly from senile plaques where the proteins are accumulated. The levels of CSF-Tau protein correlated positively and significantly with the serum levels of copper and also with the serum copper/zinc ratio. Clinical ratings showed slight improvement after 3 weeks treatment with clioquinol in this open study.

We have conducted a preliminary study of the optimum conditions for a therapeutic effect of ganglioside GM1 in Alzheimer''s disease. Five patients with the early onset form of Alzheimer''s disease (AD type I) received the ganglioside by intracerebroventricular administration for 12 months. Bilateral stereotactic punction of the frontal horns of the ventricular system was performed, and shunt catheters were implanted and connected to a programmable pump. The optimum GMI dose varied between 20 and 30 mg/24h. Neurological, neuropsychological, psychiatric and neurochemical examinations were performed 7 days before surgery and on days 30, 90, 180 and 360. No patient found the surgery difficult and no patient or relative regretted that they participated in the study. The patients became more active and safer in relation to others and to performance of various activities from day 90. The cerebrospinal fluid level of the monoamine metabolites homovanillic acid and 5-hydroxyin-doleacetic acid and the neuropeptide somatostatin increased.

In dementia disorders, it can be assumed that the pathological process in the brain has been present for a long time. It is therefore of importance to have a preclinical or an early clinical diagnosis. Obviously, vulnerability genes, such as ApoE-4, can be diagnosed preclinically. As we have no treatment to offer patients with genetic risk factors, genotyping for ApoE-4 is at present of no clinical use. Trained neuropsychologists have today access to sensitive tests which reveal cognitive impairment before the disturbances reach the level of dementia. Laboratory investigations of cerebrospinal fluid have so far yielded no great results. Tau protein appears to be the most sensitive marker, but it is unspecific. Chromogranin A separates early onset from late onset Alzheimer's disease and seems to be a marker for synaptic degeneration. Synaptotagmin was also found to be reduced in patients with early onset Alzheimer's disease. Still we do not know, however, whether these proteins are early markers for degenerative processes in the brain. Laboratory investigations of blood have not yielded markers of use in early or differential diagnosis of dementia disorders. In a study at our own institute, however, we found serum-homocysteine (S-HCY) to be an early and sensitive marker for cognitive impairment. In patients with dysmentia (mild cognitive impairment), no less than 39% had pathological S-HCY levels, indicating insufficient 1-carbon metabolism.

Experience fiom a memory center at a university hospital WERNER M. LEHMA", CARL-GERHARD GO'ITFRIES, PER HELLSTROM. ALESSIO DEGL'INNOCENTI Lehmann WM, Gottfries CG, Hellstrom P, degl'hocenti A. Experience from a memory center at a university hospital. Nord J Psychiatry 1996;50:63-70. Oslo. ISSN 0803-9488.The memory center at Molndal Hospital was opened in 1993 to meet the need for outpatient evaluation, information. and treatment of patients with cognitive disturbances of various degrees. As memory disturbance is a key symptom in dementia, memory complaints in elderly people may be the fmt symptom of a slow or rapid development of dementia, but in many cases they only reflect a decline in short-time memory that is considered normal in aging. During the period January 1993 to June 1994, 406 patients with subjective memory complaints were received at the center. About one-fourth of these patients were found to be demented and 35% to have mild cognitive dysfunction. The latter group is the most important target group for therapeutic measures. Although dementia, with few exceptions, is not reversible today, certain pharmacologic treatments are believed to slow down its progress. About 40% of the patients had no measurable cognitive disturbance, but depressive and neurotic symptoms were relatively common among both these patients and the others. Measures taken at the memory center were information, advice, brief psychotherapy, support of relatives, and pharmacotherapy aiming at alleviating disease-related symptoms like depression and emotional disturbance or at supplementing neurotropic vitamins or other essential substances. Our experience indicates that early diagnosis combined with these measures may slow down the progress rate of dementia, enhance the quality of life, and delay institutionalization for many patients. Nord J Psychiatry Downloaded from informahealthcare.com by University of Otago on 01/08/15 For personal use only. Nord J Psychiatry Downloaded from informahealthcare.com by University of Otago on 01/08/15 For personal use only. Nord J Psychiatry Downloaded from informahealthcare.com by University of Otago on 01/08/15 For personal use only.

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