in all demented groups the contents of gamma- aminobutyric acid were significantly decreased. The changes of sodium and potassium correlated signifi- cantly with the changes of amino acid transmitters. Thus, also in dementia sodium/potassium ratios are

useful as an index to cell death. The severe reduction of Asp, Glu and Tau levels in some demented cases may reflect the degeneration of cortical and hip- pocampal pyramidal cells.

41. Immunocytochemical and histochemical comparison of amyloid plaques in Alzheimer's disease and mouse scrapie

P. Eikelenboom, J.P. Brion, P.A. McBride and M.E. Bruce (Amsterdam, The Netherlands; Brussels, Belgium; Edinburgh, UK)

Cerebral amyloid plaques in experimental mouse scrapie are analogous in structure to senile plaques in Alzheimer's disease, consisting of amyloid cores sur- rounded by degenerating neurites and microglia. Im- munostaining of amyloid cores with antisera to scrapie-associated fibrils was consistently positive in mouse scrapie, but negative in Alzheimer's disease, suggesting that the origin of the amyloid protein is different in the two diseases. Using antisera to either tau protein or paired helical filaments (which stain neurofibrillary tangles in Alzheimer's disease), positively-stained structures were identified at the periphery of plaques in both scrapie and Alzheimer's disease. These structures were probably degenerating neurites which have been identified ultrastructurally, but which in scrapie

contain no paired helical filaments. Specific monocyte markers indicated that the microglia associated with both scrapie and Alzheimer plaques were not blood-borne macrophages. Also, no serum proteins could be demonstrated in or around plaques in scrapie; in Alzheimer's disease the only serum proteins detected were the complement factors Clq, C4 and C3. Therefore, blood-brain barrier defects are unlikely to be important in the development of pla- ques in either condition but complement factors may be specifically involved in Alzheimer's disease. Im- munostaining for GFAP demonstrated that, in addi- tion to microglia and neurites, reactive astrocytes were consistently associated with plaques in both scrapie and Alzheimer's disease. These results suggest that, although amyloid protein in scrapie and Alzheimer's disease differs, similar mechanisms are likely to be involved in the develop- ment of plaques in the two diseases.

42. Desglycinamide-arginine-vasopressin penetrates to the central nervous system and in- teracts with monoamines in human subjects

J. Jolkkonen, H. Soininen, M. Lehtinen and P. Riek- kinen (Kuopio, Finland)

Vasopressin is a nonapeptide which, in addition to functioning as a classical hormone, may affect memory and learning processes. Desglycinamide-arginine-vasopressin (DGAVP) has the same behavioral properties as vasopressin, but is practically devoid of peripheral hormonal effects. Our purpose was to study whether intranasally ad- ministered DGAVP enters the central nervous system in human subjects by measuring DGAVP levels in CSF. The effect of DGAVP on monoaminergic neurotransmission was assessed by measuring monoamine metabolites in CSF. A single dose of 2 mg D G A V P (Org 5667) was ad- ministered intranasally to 37 patients who needed a diagnostic lumbar puncture. CSF was taken in dif- ferent patients at an interval between 5 and 240 min after administration. Control patients had no

DGAVP administration. DGAVP in CSF was measured by using radioimmunoassay. Monamine metabolites were determined using HPLC with electrochemical detection. Detectable levels of DGAVP in CSF were found 5-30 min after applica- tion, but the levels declined rapidly during the next 60 min. The levels of monoamine metabolites, homovanillic acid and 5-hydroxy-indoleacetic acid in- creased two-fold 150-180 min after DGAVP ad- ministration, whereas levels of 3-methoxy-4-hydroxy- phenylglycol, the major metabolite of noradrenaline, remained stable during the 240 rain monitored. Intranasal administration and use of an analogue devoid of hormonal effects, which allowed the appli- cation of large doses of DGAVP, seem to be impor- tant for access to the central nervous system. In addi- tion, the mechanism of action of DGAVP may involve monoaminergic systems. The present findings are important in clinical application, particularly in treatment of cognitive impairment.

43. Neuropsychological pre-morbid risk testing in familial Alzheimer's disease: MRI neuroimaging and clinical diagnosis correlations

Gary D. Miner, Linda A. Miner, William S. Two familial Alzheimer's disease (FAD) families (49 Yamanashi, Patrick D. Lester and Ralph W. Richter subjects) appearing to fit a dominant gene model of (Tulsa OK, USA) inheritance and with homogeneous age-of-onset in

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the late-40's were studied with a battery of neurop- sychological tests to detect early 'pre-disease' risk factors. Also, MRI brain scans have been conducted on some of these subjects. The first of subjects has been clinically diagnosed with FAD 2 years following the neuropsychological testing. Analysis of 6 of the neuropsychological tests (Lezak's Tinkertoy Test; Benton's Controlled Word Association, Judgment of Line Direction, Facial Recognition, and Visual Re- tention; and Shipley's Verbal Abstractions) indicate that the experimental subjects apparently fall into 2

groups, whereas the control subjects score within a single group. The clinically diagnosed FAD subject and another subject showing cortical atrophy by MRI both appear in the 'at-risk' group, providing evidence that there are pre-morbid neuropsychological risk- factors that with further identification and under- standing should aid in early diagnosis. Our studies of FAD indicate that this disorder may fall into more than one group based on age-of-onset: mid-30"s, late- 4()'s and mid-60"s are possible groups.

44. Plasma and cerebrospinal levels of methionine-enkephalin in senile dementia of the Alzheimer's type

Ralp W. Richter, Jimmie L. Valentine, Nicholas P. Plotnikoff, Marion S. Patten, Jonathan Bennett, Carol Cromer and Gary D. Miner (Tulsa OK, USA)

Earlier studies by Sulkava et al. (1985) indicated that CSF beta-endorphin levels are depressed in SDAT (senile dementia of the Alzheimer's type). Since the pro-hormones, pro-opiomelancortin (the precursor of beta-endorphin) and pro-enkephalin A (the precursor of methionine-enkephalin) are fre- quently found in areas of the brain which are impli- cated in Alzheimer's disease, prompted us to investig- ate CSF and plasma levels of met-enkephalin in patients with SDAT. The blood plasma levels of met-

enkephalin were significantly depressed in SDAT pa- tients when compared to age-matched controls with no signs of dementia. Plasma levels of met- enkephalin were elevated in the age-matched con- trols when compared to younger age volunteers in- dicating that increases in plasma levels of met- enkephalin may occur as part of the natural aging process. CSF levels of met-enkephalin in SDAT were also lower than age-matched controls. These preliminary findings suggest that met-enkephalin may in some way be related to the depletion of this potential neurotransmitter during progression of the disease.

45. Differential diagnosis between Alzheimer's disease and vascular dementia: evaluation of common clinical methods

Timo Erkinjuntti, Raimo Sulkava and Jorma Palo (Helsinki, Finland)

A prospective series of consecutively admitted de- mented patients were examined in order to evaluate the role of common clinical methods in the dif- ferential diagnosis between Alzheimer's disease (AD) and vascular dementia. Patients fulfilling the DSM-III criteria for vascular dementia were divided into multi-infarct dementia (MID) and probable vascular dementia (PVD), the latter including also cases with combined vascular and degenerative de- mentia. The series consisted of 68 patients with AD, 79 with MID and 46 with PVD. These groups did not differ in regard to sex, age or degree of dementia. Absence of cardio- and cerebrovascular diseases dif- ferentiated AD from MID and PVD. Also absence of corticospinal tract signs and gait disorders differenti-

ated AD from MID and PVD and absence of bulbar signs AD from MID. Absence of infarcts and white matter low attenuation on CT differentiated AD from MID and PVD. Brain infarcts were seen on CT in 88.6% of patients with MID and in 41.3% with PVD, but in only one patient with AD. Ischaemic scores also seemed to be useful in the differential diagnosis between AD and vascular dementia. Quantitative neuropsychology, EEG, routine cerebrospinal fluid and other laboratory investigations, including serum glucose and plasma lipids, seem to be less valuable. By now 5 patients with AD, 19 with MID and 5 with PVD have been subjected to post mortem neuropathological examination. Accuracy of clinical diagnosis of AD was 100%, of MID 89.5% and that of PVD in regard to MID 60%. Clinical differentiation of combined degenerative and vascular dementia from AD and MID presented the greatest problem.

46. Psychological patterns in Alzheimer's disease

Manuela Guerreiro and Carlos Garcia (Lisbon, Portugal)

Trying to figure out the psychological pattern(s) of Alzheimer's disease, 51 patients with this diagnosis were tested with a battery of 15 tests.

All patients had progressive dementia confirmed by neuropsychological evaluation. Their medical history gave no clues for an etiology, neurological examina- tion disclosed no significant neurological signs besides the mental defect and all patients had low Hachinski scores. CAT scan excluded stroke or

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