S296 Dementia, Cognitive Decline, Aging

5-12-19 Striatal uptake of the dopamine reuptake ligand [“C]p-CR Is reduced in Alzheimer’s disease assessed by PET

Juha 0. Rinne, Nina Sahlberg, Hanna Ruottinen, Kjell Nagren, Pertti Lehikoinen. Deparfmenf of Neurology and Turku PE%cente& University of Turku, Turku, Finland

Post mortem studies have shown changes in brain dopaminergic system in Alzheimer’s disease (AD). These changes have been suggested to be asso- ciated with extrapyramidal symptoms of the patients. The few previous in viw studies have shown no change in brain dopamine system in AD. In this study striatal dopamine reuptake sites were studied with PET in twelve patients (5 women, 7 men: mean aoe 65.0 f 7.2 vears) with Alzheimer’s disease (AD).

A c&aine analogue,[“C]B-CFT was used as a radioligand. On aver&se 10 mCi of [llCIS-CFT was injected intravenously and a dynamic 80 min study was perfoimed with a Ering whole body PET scanner-(ECAT 931/08-12). The specific striatal uptake of [“C],¶-CFT was calculated as (region-cerebel- lum)/cerebellum as an average ratio between 60 to 60 min.

In AD the mean [“C]B-CFT uptake value in the caudate nucleus was 1.57 (SD 0.06), which was significantly lower than the age adjusted value in the controls (2.02, SD 0.09; p = 0.002). The corresponding values in the putamen were 1.54 (0.06) for AD and 1.96 (0.09) for controls (p = 0.002). The extrapyramidal symptoms of the patients evaluated by the motor part of the Unified Parkinson’s Disease Rating Scale (UPDRS) had a negative correlation with the [” C]j+CFT uptake values both in the caudate nucleus (r = -0.61, p = 0.05) and putamen (r = -0.56, p = 0.04).

The present results show that the uptake of the dopamine reuptake ligand [“C]p-CFT is reduced in AD, possibly reflecting decline in striatal dopamine transporter, and that this reduction is associated with extrapyramidal symptoms of the patients.

15-l 2-20 1 The troplcamide test in patients with dementla of Alzhelmer type and fronto-temporal dementia

A. Robles, R. Touriiio ‘, M. Noya. Department of Neurology; ‘Department of Ophthalmology: Hospital General de Galicia, Santiago de Compostela, Spain

We have applied the tropicamide test to 30 patients with probable Alzheimer’s disease (AD) -NINCDS. ADRDA criteria-, 12 with frontotemporal dementia -Lund and Manchester criteria- and 46 control subjects. We administer one drop of 0.01% tropicamide in an eye and one drop of 0.45% saline solution in the other. The pupil diameter is measured in a Goldmann pupilometer in basal condition and 10,15,20,25,30,35,45 and 55 minutes after. The results do not show differences between the pupil dilation observed in AD and frontotemporal dementia, but in both groups the pupil dilates more and faster than in the healthy control group. The best cutoff point can be one of these: Over 50% dilation at minute 25 (sensitivity = 36%, specificity = 98%), and over 36% at minute 30 (sensitivity = 73%, specificity = 67%). If we considered that the prevalence of AD in population over 40 year-old is 1.4%, the positive predictive value of the test would be 16%, and the negative 0.56%. The tropicamide test is not a diagnostic marker of the AD, though it may be helpful when we face unclear cases of cognitive failure.

5-12-21 Donepezil provides long-term clinical benefits for patients with Alzhelmer’s Disease (AD)

S.L. Rogers, L.T. Frtedhoff. Eisai America Inc, GlenpoiMe Center East, 300 Frank I! Burr Blvd., Teaneck, NJ, USA

Donepezil HCI, a piperidine, is a selective inhibitor of acetylcholinesterase which has been demonstrated in Phase II and Ill trials to improve both cognitive and global function in AD patients. This study investigates whether these clinical benefits are maintained in the long term, despite the progressive, degenerative nature of this disease.

An open label extension of a Phase II, randomized, placebo-controlled trial of donepezil was undertaken. All patients received 5 mq/day donepezil, later increasing to IO mdday, based on safety. The Alzheimer’s Disease Assess- ment Scale-cognitive subscale (ADAS-cog) and Clinical Dementia Rating-Sum of the Boxes (CDR-SB) were conducted at 12-week intervals up to 192 weeks. Data for the first 110 weeks have been analysed to date.

Donepezil produced improvements on both instruments; maximum improve- ment from baseline was observed at Week 24. The mean donepezil-no treat- ment effect sizes at 24 weeks were 4.94 and 0.80 points, compared to 5.80 and 1 .Oi points at 110 weeks for the ADA&cog and CDR-SB respectively, an increase of approximately 20%. The mean slope of change of ADAS-cog and CDR-SB score over 110 weeks corresponded to an annual increase of 6.6 and 1.8 points, less than the 9-11 and 2.4 points previously reported in untreated moderately demented patients, respectively.

These data suggest that the benefits provided by donepezil are enhanced or sustained during long-term treatment.

5-l 2-22 A randomized, double-blind, placebo controlled study of idebenone in Alzhelmer disease (AD)

L. Sabe, G. Kuzis, A. Garcfa Cuerva, C. Tiberti, M.F. Dorrego, S. Starkstein. Neni Montareses 2325 Buenos Aires 1428, Argentina

Objective: To examine the usefulness of idebenone in the treatment of proba- ble AD.

Methods: A consecutive series of 53 patients were randomized to receive idebenone or an identical placebo during a l-year period. The initial dosage was 10 mg. for the first month, 20 mg. for the second month, 30 mg. for the third month, and 40 mg. for months fourth to twelve. Every three month patients received a neuropsychological evaluation which consisted of the Mini-Mental State Exam (MMSE), the Buschke Selective Reminding Test, and the Hamilton Depression Scale.

Results: 25 patients were randomized to receive idebenone, and 28 pa- tients received an identical placebo. An ANOVA with repeated measures for MMSE scores showed a significant time effect (F (3,150) = 6.22, p < 0.0005) (both groups showed a significant decline over a one year period), but no sig- nificant group x time effect (the decline in MMSE scores was similar for both groups). An ANOVA with repeated measures for Buschke Selective Reminding Test scores showed a significant time effect (F (3,150) = 2.95, p 4 0.05) (both groups showed a significant decline over a one year period), but no significant group x time effect (the decline in Buschke SRT scores was similar for both groups). An ANOVA with repeated measures for Hamilton Depression Scale scores showed no significant time effect (F (3,150) = 14, p = NS) (both groups showed similar scores over a one year period), and no significant group x time effect (scores were similar for both groups).

Conclusion: ldebenone did not demonstrate to be a useful treatment for the cognitive deficits of AD.

5-l 2-23 Decrease of N-CAM adhesion molecule in serum of advanced Alzhelmer’s patients

E. Sacerdote de Lustig, S. Kohan, L. Todaro, A. Famulari, R. Dominguez, E. Farias. Research Area, lnstitote of Oncology Angel H. Rofk~, Sir/o Libanes Hospital, Buenos Aires, Argentina

Background: Alzheimer’s disease is characterized by a significant loss of synapsis on neocortical and hippocampus tissue correlating with cognitive deficit. This alteration may be associated with a deficient expression of some neural adhesion molecules belonging to the Ig superfamily as N-CAM involved in synaptic plasticity. memory and learning. Intracranial injections of antibodies against N-CAM during the protein synthesis dependent phase of memory consolidation disrupts the memory of the training experience.

Methods and Reaub: In order to corroborate the relationship between N-CAM and memory loss we assessed the presence of this molecule in serum of probable Alzheimer and vascular dementia’s patients and age matched controls.

A strong Western band of 150 kDa N-CAM was expressed by 13 controls, while 8 vascular demented patients and IO moderate Alzheimer’s patients showed a lower thin band. A total absence of this N-CAM molecule was found in serum of 12 advanced Alzheimer’s patients.

Conclusions: These results suggest that N-CAM could be a good marker of disease progression and could open a new therapy avenue.

5-l 2-24 Psychosocial profiles at the preclinical phase associated with early onset non-familial Alzheimer’s disease

Luis M. Sbnchez, Roberto Cantero, Antonio S. Frumento. Health Sciences Facult): National University of Enfre Rios Concepcidn de/ Uruguay Uruguay

The objective and subjective personal losses and the dynamics of the relational and communicational fields during at least ten years before the initial signs, were studied for 52 early-onset non-familial Alrheimer’s disease patients (age ranged 59 to 78 years, mean 71 years) selected by NINCDS-ADRDA criteria, and compared with 68 age, sex, labor profile and educational level-matched normal ageing control subjects. The dates and informations were recalled from the family’s caregivers by means of seven applications forms for the personal losses, seven for the dynamics of the relational fields and other seven for the communicational fields. The dates and information were processed by the SYSTAT statistical PC program, and risk diagrams for dementia of this type designed. We concluded that the occurrence of non-replaced non-wrought per- sonal losses on the major relational/communicational vectors of development during their health life, is associated to the installation of this type of demen- tia and also the relational and communicational diagrams of the Alzheimer’s disease subjects are clearly unbalanced and less plural compared with the normal ageing control ones. A neat and progressive reduction of the rela- tional and communicational dynamics took place in these AD subjects starting from the losses happened previously. A routine laboral profile under isolated

Dementia, Cognitive Decline, Aging S297

scene, or/and a limited and non-plural relations with abstract entities (but not with the educational level), or/and a generalized low relational dynamics plus the previous conditions (specially non-replace non-wrought losses), increased exponentially the risk of this type of Alzheimer’s disease.

5-l 2-25 The dementiation unchained by extreme situations: Experimental Alxheimerk disease cases?

Luis M. Sdnchez, Roberto Cantero, M. del C. Rubano. Health Sciences Faculty National Univesity Of Entre Fibs, Concepci6n del Uruguay,

This research began as soon as we could find dementiation’s cases in captives from the last dictatorship “legal” prisons, and it was afterwards extended to dementiations unchained by familiar catastrophes and under a lethal disease. We used the medical histories, lawsuits and institutional reports, and extensive interviews with the attending professionals (physicians, psychologists, psychi- atdsts, neurologists) and to the caregivers and nearest relatives to gather the necessary information. We now expose here only eleven cases, seven of them dead at present, from 26 to 62 years old (seven male). In three cases the dementiation affected only certain areas of the social transactions (at work, acute introspection, aggressiveness) but didn’t go far beyond. In the other eight cases the installed dementiation was progressive and irreversible, all fin- ished in death, beginning with a relational and communicational blockade with few ups and downs, followed by a temporal and spatial notion losses, inability to take a decision (starting with incoherent decisions and subsequently any decision at all), a progressive inability when deciding what to wear according to the climate and then inability to dress, or to wash without assistance. Verbal communication is interrupted later, incoherents repetitive words are emitted and then inexistents words are made up. Finally they lost the ability to sit up alone and hold up their heads, concluding in animmobile state. These patterns seem like early onset non familiar Alzheimer’s disease but at fast rate under persistent relational and communicational blockade, suggesting a new way to explore the Alzheimer’s aethiology.

5-l 2-26 Creutzfeltd Jakob disease, three cases report R.E. Santiago, G.C. Cuevas, A. Rivas, I.J. Almanza, D. Reyes, A. Molano. Hospital de Especialidades Centm M&&X National Siglo XX/ IMSS, M6xico OF; Mexico

The CreutzfeltdJakob disease (CJD) is an human spongiforme encephalopa- thy transmitted for ptiones and affects to the netvous central system in slow, progressive and mortal form. CJD can be divided into three categories: spo- radic, iatrogenic transmission and familial forms. The purpose of the present work is the report three cases of the sporadic form.

Case 1. 50-year-old housewife with subacute onset, depressed state and gradual failure of memoty. During the next six months she lost all interest in the house, progressive lost of the intellectual capacity, confusion and visual hallucinations.

The neurological exploration showed inattention, disorientation, the mus- cular force is normal with exaggerated deep tendon reflex. Two weeks later she became confused, rigidity, myoclonic jerk in the extremities and bilateral Babinski signs. The routine examination of the cerebrospinal fluid was nor- mal. The EEG showed burts-suppression type of periodic pattern. The MRI showed cortical and subcortical atrophy. The brain biopsy showed astroglial proliferation and neuronal losses.

Case 2.53 year-old men, Medical. He initiates with anxiety, depression and insomnia. The symptoms is progressive and two months more late, he became disoriented, failure of memory and visual and auditory hallucinations.

The neurological examination showed drowsiness, disoriented, short at- tention span, poor memory. Quadriparesy, exaggerated tendon reflex, and right Babinski sign. His hospital course was one rapid deterioration became comatose with myclonic jerk.

The cerebrospinal fluid with a modest elevation of protein. CT scans and MRI was normal. His EEG showed slow wave activity, during next week with burts-suppression type of periodic pattern. His cortical biopsy with neuronal degeneration, gliasis an spongiform change.

Case 3. 56 year-old woman, began to have dizziness, vertigo, depression, four months more late desorientation, poor judgment drowsiness. As these symptoms worsen, she was admitted to hospital. The neurological exploration showed comatose, rigidity and myoclonic jerk and EEG showed burts-suppres- sion. The CT scan and IRM is normal, with three months showed cortical and s&cortical atrophy.

The previous cases demonstrate a classic evolution of the illness with behavioral, abnormalities, defects in higher cortical function, signs of pyramidal and extrapyramidal dysfunction and myoclonic jerk. A only case showed the rapid installation of cortical and subcortical atrophy.

5-l 2-27 A case-control study of risk factors on Alzheimer’s Disease from the group of seafares in Shanghai, China

Xiao Chu Shen. Shanghai Ocean Hospital, Shanghai, PR China

A case-control study of risk factors on Alzheimer’s disease among the group of sea farer at Shanghai district in China. Shen Xiaochu, et al. Shanghai Ocean Hospital, Shanghai 200031.

A case-control study to assess the possible risk factors associated with Alzheimer’s disease (AD) among Chinese sea farer in Shanghai district was conducted on 36 clinical diagnosed AD patients and 72 non-demened non-sea- farer as control matched by age, sex, nationality, residential area. Found that the factors significantly with AD cases were: not only family history of dementia in first degree relatives, family history of psychoses in first degree relatives, few interests and heavy negative life events during individual life time, but also antecedent of head trauma and smoking.

I__I 5 12 28 Skeletal muscle dennervation in Alzheimer’s disease (AD)

Roberto E.P. Sica, Carlos Mangone, Silvia Pereyra. Neurology; Ramos Mejia Hospital School of Medicine, Buenos Aires Univetsi~ Argentina

It is a common observation that, along with the intellectual impairment, most of AD patients become thinner and their muscles bulks smaller, while their strength progressively diminishes. Little attention has been paid in the literature to the state of the peripheral nervous system in these subjects (Thomas et al. 1962; Nousiainen et al. 1991).

Material: Fourteen patients with probable AD were selected for this in- vestigation. All them were younger than 60 years old and had not had other neurological diseases or other clinical illnesses or intoxications. Results were compared with 16 healthy controls matched by age.

Methods: a) Estimation of the numbers of functional motor units (MUs) and their sizes were carried out in the thenar and soleus muscles. b) Nerve conduction velocity studies were performed in the median and deep peroneal nelves. c) Conventional electromyography was carried out in the deltoid and tibialis anterior muscles.

Results: a) Estimation of the number of MUs, I.-Thenar muscles: in controls the lowest estimate was 225. Only one patient had a number within the control range. The patients mean (167 +59) significantly differed (p < 0.001) from controls mean (295 +50). II.- Soleus muscle: the lowest estimate in controls was 407. Three patients had normal values. Patients mean (345 +107) significantly differed (p < 0.001) from controls (665 +156). b) MUs sizes: there was not significant difference between the amplitudes of individual MUs in patients and controls. c) Nerve conduction studies, I.- Maximal motor conduction velocity: all patients were within the control range. II.-‘Motor terminal latency: median motor terminal latency was prolonged in 7 patients; deep peroneal terminal latency was prolonged in 2 patients. Ill.- Median sensory conduction velocity studies were normal in all patients. IV.- Median nerve proximal motor conduction velocities were normal In all patients. d) Conventional EMG showed diminished interference pattern in all patients. Most of the remainer MU potentials were fragmented or poliphasic. Fibriilation potentials and positive sharp waves could be found in 3 patients.

Conclusions: The present findings have shown that losses of whole skele- tal muscle motor units occur in AD. This behaviors cannot be attributed to disorders of the peripheral nerve, for conduction velocities, either motor, sen- sory or proximal, were well within the control ranges. Taking together all these observations, it is possible to assume that some skeletal muscle dennervation occurs in patients with AD and the primary affected structure might be the motoneurone soma, leading to a neuronopathy which may justii the loss of functional motor units and the prolonged motor tenninal latencies. The fact that the remaining motor units did not enlarge their territories to compensate dennervation, as happens in other dennervatory conditions, suggests sickness of the remainer functional motoneurones.

5-l 2-29 E$I& and implicit memory deficits in Alrheimer’s

E. Stefanova, G. OciC, L.J. riropadja, G. TomiC, A. MiloviC, S. GoluboviC, G. ZlatiC, J. DjordjeviC, D. Pavlovik, P. Smiqkovi& S. rugi&. Institute of Neurolog): CCS, Dr Suboti~a 6, Belgrade, Yugoslavia

Memory dysfunction is a primary diagnostic criterion and one of the earliest clinical sign of Alzheimer’s disease (AD). The nature of memory deficit is as- sumed to represent a unitary profile. We tested 25 patients with very mild AD and 20 amnestic patients operated on ruptured aneurysm of artery communi- cating artery (ACoA) with various tests of memoty function. The patients with very mild AD and amnestic group had very similar memory deficits (qualita- tively and quantitatevely) characterized by impaired memory span, disturbed learning and consistency of recall. Patients with ACoA syndrome showed ab-