$368 Wednesday, November 9, 2005 Poster Abstracts

8 different directions for 1 second to displace their centre-of-pressure (COP) to match targets on a screen. Clinical measures comprised part III of the Unified Parkinson's Disease Rating Scale (UPDRS). Results: Static sway area was reduced to 66 ± 5% (SEM) of untreated values with GPS. Dynamic task reaction time improved to 87 d_ 14% of untreated values, while target hold achievement time and total task time remained unchanged. Target overshoot increased to 133 d- 14% and CoP wandering to 120 d- 22% of untreated values. Total UPDRS fell to 65 d- 9%, with reductions in rigidity and mxial subscores, however motor scores correlated poorly with static and dynamic balance measures. Conclusion: GPS has differential effects on static and dynamic postural control with improvement in static sway but not in dynamic stability. The effects of GPS on postural control appear to be independent of its other effects on limb and axial function.

1057 Synergetic efiect of ALflleiqler and Lewy-body changes on dementia

Saito, y~,2, Kanemaru, K 2, Arai, T 2, Sawabe, M ~, Murayama, S ~. 1Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.." :Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan

Objeelive: In order to clarify the relationship between Alzheimer and Lewy-body type changes in dementia. Method: Serial 1395 autopsy cases from a geriatric hospital since 1995. The mean age was 80.6 with male to female ratio being 758:637. Parkinsonism and dementia were retrieved from the clinical records. Lewy body dementia (LBD) includes dementia with Lewy bodies (DLB) and Parkinson disease with dementia (PDD), presenting with Lewy body-related neuronal degeneration involving the peripheral autonomic, the nigro-striatal and the limbic/neocortical systems. The diagnosis of Alzheimer disease (AD) was based on Braak's senile plaque (SP) Stage C and neurofibrillary tangle (NFT) stages equal to or above IV. Each case was classified into A D + L B D , A D + L B D + , AD LBD+ and AD LBD . Apolipoprotein E (Apo E) genotyping was detemfined in 1,114 from the 1,395 cases. Results: 120 cases ([8.6%)were categorized into A D + L B D - , 45 ([3.2%) A D - L B D + and 16 (1.1%) AD+LBD+. The series included 28 ([2.0%) PD cases, 16 (1.1%) of which showed dementia and was classified into one A D + L B D + and 15 AD LBD+ cases. The male to female ratio in A D + L BD , A D + L B D + and AD LBD+ was 0.53, 0.78 and 1.1, respectively. AD LBD+ with SP Stage C/NFT Stage 0-III covers 29% of all A D - L B D + , higher than 11% of A D - L B D - . The apoE z4 frequency in AD+LBD-, A D + L B D + , AD-LBD+ and AD-LBD- was 25%, 27%, 15% and 9.3%, respectively. Discussion and Conclusion: Our approach, avoiding confusion in tile nanffng of AD, DLB and PDD, confirms a mutual aggravating effect of AD and LBD changes causing dementia.

1058 Tumor Necrosis Factor-alpha blocking in a experimental model of parkinsonism

J. Salvalierra 1, R. DurAtl 1, Giner p .2 M. J. Ruiz-Magafia 1, B. Morales 1, F. Barrero 1, F. Alba 1, I. Prieto 3, M. Ramirez 3, F. Vires 1. llnstituto de Neuroeiozeias, Faeultad de Medieina, University of

2 Granada.." Unidad de Medieina bzterna, Antequera; 3Unit of Physiology, University of Jaen, Span

Background: Recent studies (Nagatsu et al., 2005) have found increased levels of proinflanmlatory cytokines, such as tmnor necrosis factor (TNF)-alpha and interleukin (IL)-I beta in the nigrostriatal region of postmortem brains of patients with sporadic Parkinson's disease (PD). Additionally, PD patients have increased serum levels of TNF-alpha that correlate with manifestations of neurological symp- toms (Gribova et al., 2003). Etanercept is a recombinant human TNF receptor fusion protein which blocks TNF-alpha, modulating inflam- matory processes. The objective of tiffs research was to assess if

etanercept, protects against experimental parkinsonism. We postulate that blood-brain barrier is altered in this animal model of parkinso- nism allowing subcutaneously given etanercept to reach therapeutic levels in the cerebrospinal fluid. Method: Thirty male Wistar rats were divided into five groups: (1) control group; (2) sham operated group, which received 4 pL of vehicle injection into striatum of both sides; (3) caudate-putamen (CP) lesion group, which received bilateral injections of 32 gg of 6-OHDA/ 4 pL into striatum; ([4) CP lesion group treated every 5 days with s.c. injections of 5 mg/kg body weight etanercept. After tile second injection, rats were lesion into CP and (5) substantia nigra (SN) lesioned group, which received bilateral administration of 6-OHDA into SN. Since one month before the lesion to one month post-lesion, motor activity of rats was measured by infrared beams, using a Motor Activity Monitor Letica LE8811. Student t test was used to statistical analysis. Results: Except during the six days post-lesion, there were no significant differences in the spontaneous motor activity among the groups. Conclusion: The subcutaneous administration of etanercept did not protect against experimental parkinsonism, probably because it can not cross the blood-brain barrier. Currently we are carrying out experiment adininistering intraventricalar etanercept to confirm our conclusions and assess therapeutic effects.

1059 Age at onset of Parldnson's disease in women is associated with age at menopause

Savettieri, G, Ragonese, P, D'Amelio, M, Callari, G, Morgante, L, Salenri, G, Epifanio, A, Morgante, L. University Of Palermo, Department Of Neurology, Oftabnology, Otolaringology, Psy University of Messina, Department of Neuroscience

Heading: Aim of this study was to verify if the age at onset of Parkinson's Disease (PD) is modified by factors modulating the estrogenic, stimulation during women's life. Background: EpidemJological and experimental studies suggest an association between factors reducing the estrogenic stimulation during women's life and PD risk. Methods: We included women affected by PD according to validated criteria, with a Mini Mental State Evaluation score > 24. Cumulative length of pregnancies, age at menarche, age and type of menopause were investigated through a structured questiommire. Linear and logistic regression analyses were used to estimate the association between the investigated variables and age at PD onset. Crude and adjusted OR, 95% CI and two-tailed p values were calculated. Results: We included 145 women affected by idiopathic. PD. Linear regression analyses showed a significant association between age at PD onset and age at menopause (adjusted r square -- 0.07; p - 0.002). A linear association approximating the statistical significance was also observed between PD age at onset and cumulative duration of preg- nancies (p - 0.05). At Logistic regression analyses age at PD onset, dichotomised according to the median of its distribution (61 years), was only associated with age at menopause ([OR 0.94; 95% CI 0.88- 1.00; p 0.06) approximating the statistical significance. Conclusions: These results further support the hypothesis regarding the role of endogenous estrogens in the development of PD. Our data also indicate an association between hormonal stimuli during fertile life and age at PD onset.

1060 Investigation on potential effects of continuous administration of rotigotine on sleep architecture in rats

ScheUer, D 1, Dummller, N 2, Porsolt, R 2. 1Sckwarz Biosciences, Monheim, Germany; 2Porsolt & Partners Pharmacology, Boulogne-Billancourt, France

Poster Abstracts Wednesday, November 9, 2005 $369

Background: Rotigotine is a non-ergolinic dopamine agonist being developed for Parkinson's Disease. To achieve continuous dopami- IIergic stimulation, a fommlatioli of rotigotilie was generated which after subcutaneous adlifiliistratioli persistently delivers the compound over more titan 48 hours and provides stable plasma levels. In order to evaluate whether rite continuous receptor stimulation could affect the sleep and diurnal rhythms, the present study was conducted. Methods: Rats were chronically instrumented with EEG and EMG electrodes and EEG and motor activity pattern were recorded continuously over six days. REM sleep periods could clearly be separated from periods of slow-wave-sleep (SWS) and awake states. Results: Rotigotine (applied s.c. at a dose of 0.5 or 5mg/kg every second day for 6 days) did not affect the sleep architecture even at the high dose (15 mg/kg): rotigotine did not affect the time to onset of REM or of slow wave sleep; it did not affect the duration, the number and distribution of REM sleep, of slow wave sleep nor of wakefulness. For comparison, IIomifelisilie given daily (116 mg/kg p.o.) markedly influenced sleep pattern. Conclusions: The continuous administration of rotigotine although providing sustained dopamine receptor stimulation does not disturb the sleep arclfitecture and diurnal activity pattern in rats. According the principles arid laws on animal experimentation, all efforts were made to miliimize potential suffering of the animals.

1061 Continuous stimulation of dopamine receptors by a continuous delivery of rotigotine in a rat model

SeheUer, D 1, Kehr, j2.1Schwar z Biosciences, Monheim, Germany; 2Karolinska Instituter, Stockholm, Sweden

Background: Rotigotine is a non-ergolinic dopamine agonist being investigated for Parkinson's disease (PD). In order to achieve stable plasma and brain levels in experimental studies, a slow release fommlatioli has been developed. Using tiffs fommlatioli, the pre- sent study was conducted to demonstrate using microdialysis tech- rdque fflat the dopamilie receptors are continuously stimulated by rotigorine. Methods: A microdialysis probe was implanted into the striatum of freely moving rats (iJerfusate: Ringer solution, flow-rate: 1 gl/min; fraction volume: 20 gl). Rotigotilie (10.5 mg/kg as slow release fommla- tioli) or vehicle was injected subcutaneously. Rotigotilie and dopalifilie concentrations were determined by microbore HPLC/ECD. Locomo- tor activity was recorded using an automated system. Results: After injection, dialysate concentrations of rotigotine increased reaching a plateau of 2.32±0.68 nM at 34hours after adlifiliistratioli (it _ 6 rats) and remained at that level for at least 48 h. The extracellular dopamilie levels decreased colicomitalitly to about 20% of the control levels where ffley persisted. Although the total locomotor activity increased, the diurnal pattern was unchanged. Conclusions: In this study, the administration of rotigotine as a slow release formulation leads to a stable extracelhilar level of the compound wifffili the brain. Colicomitalitly, the level of extracellular dopalifilie is reduced. As presynaptic dopalifilie receptors control the synthesis of dopamilie, the results illustrate that ffle continuous delivery of rotigotine stimulates presynaptic doparnine receptors continuously. According the principles and laws on animal experi- mentation, all efforts were made to minimise potential suffering of the anililals.

1062 Flibanserin but not buspirone reduces levodopa-induced dyskinesia in RGS9-defident mice

Schwarz, J, Strecker, K, Ohm, S, Beck, J. Dept. Of Neurology, University of Leipzig, Germany Monitoring Force, ~uenster, Germany

Movement disorders or dyskiliesia are common side effects of IIeuroleptic drugs which are used to treat psychoses and levodopa

which is used to treat Parkinson's disease. Dyskinesia resulting from neuroleptic or levodopa treatment, have been attributed to alterations of the nJgrostriatal dopalifilie pathway. RGS9 is a GTP-hydrolase activating protein that specifically accelerates the temfination of dopalifine D2 receptor (DRD2) signalling. RGS9 deficient mice, therefore, bear an indirect gain of function of DRD2. Surprisingly, these mice display striking abnormal involuntary movements following pretreatment with reserpine and subsequent application of levodopa.

To explore the effect of flibaliserin versus buspirone on L-DOPA induced dyskinesia in reserpinized wild-type (wt) and RGS9-ko mice.

Here, we confirmed the increase in abnormal involuntary move- ments. Addition of flibanserin resulted in a "normalization" of these increased involuntary movements in mutant animals to the level of wt alfimals. In wt animals there was no significant effect of flibaliserin.

To the contrary, buspirolie had no effect on involuntary movements in either wt or RGS9 deficient mice.

Our data confirm that activation of 5-HTIA receptors via the specific agonist flibanserin can reduce dyskinesias in a genetic mouse model for drug-induced dyskinesias. On the other hand, buspirone, a rather non-specific cOlilpoulid does not have any effect on this type of movemelit disorder in wt and RGS9 deficient IIlice.

1063 Prevalence of Paxkinson's disease in Thai community dwelling dderly

Senanarong, V 1, Harliphaduligkit, K 1, Pouligvarili, N 1, Wannasaeng, S ~, Chakorn, T ~, Towattrakul, W 1, Jalirjumrus, Pl,

l 1 Chakorn, U ~, Sukhatungka, K ~, S,iboonroung, A , Lertakyamanee, J , Udompunthurak, S 1, Cummings, JL ~, Doody, RS ~. 1Faculty of Medicine Siriraj Hospital, Mahido! University, Bangkok, Thailand; 2Department of Neurology, David Geffen School of Medicine at UCLA, LA, USA; 3Alzheimer's Disease Center, Baylor College of Medicine, Houston, Texas, USA

Objectives: To survey the prevalence of Parkinson's disease in Thai elderly living in the catchment areas of Siriraj Hospital's primary care unit in Bangkok during the year 2004 and to assess the cognitive status of these elders. Subjects and Methods: We surveyed the elderly aged 60 and over living in the catchilielit areas of Siriraj Hospital 's primary care unit. We screened individuals for parkinsonisli1 and diagnosed Parkilison's disease (PD) according to standard criteria. Standard neuropsycholo- gical tests were used to detennine cognitive function. We determined the frequencies of mild cognitive impairment (MCI), and dementia among these elderly. Results: Of 913 elderly who were screened, 26 had incomplete data and were excluded from analysis. 321 (36.19%) were men and 77.79% had education of 4 years less (only 4.74% had more than 12 years of education). 69 had parkinsonism from screening questions on bradykinesia and rest tremor. 60 were found to have parkinsonism by neurological exalifiliation. Exclusion of secondary causes of parkili- sonism or atypical PD was made. 11 (1.24%) were diagnosed as PD. Among 887 subjects, 45 (5.07%) had dementia and 172 (19.39%) had MCI. Mean age of those with MCI was 71 .:16 (16.90), of dementia was 77 (8.42), and of those without MCI or dementia was 68 (16.25), p < 0.000. 18.2% (2/11) of subjects with PD had dementia, 27.3% (13/11) had MCI, and 54.5% (16/11) had normal cogtfition. Conclusion: Prevalence of PD in Thai population was lower than that in Western countries. Half of ilidividuals with PD had either cognitive impairment or dementia.

1064 An analysis of tile relationship between muscle sympathetic nerve activity and cardiac 123I-metaiodobenzylguanidine uptake in patients with Parkinson's disease