$304 Wednesday, November 9, 2005 Poster Abstracts

(MCI) and age-matched controls. The participants also underwent structural magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) of the lffppocampus to derive estimates of lffppocampal atrophy and concentrations of N-acetyl aspartate (NAA), myo-inositol (mI), choline and creatine. 2DGE data was analysed using MELANIE-3 software. Remlts: @proximately 220 silver-stained protein spots from plasma were matched between the three subject groups. Of these, approxi- mately 14 were significantly different between cases and controls (p < 0.05). Hippocampal NAA was significantly reduced in AD compared to controls. Ongoing data analysis will exanffne whether differentially expressed plasma proteins in AD correlate with biochemical markers of hippocampal atrophy. Conclnsion: A panel of plasma proteins appears to be differentially expressed in AD. MR spectroscopy demonstrates sigtffficant reductions in hippocampal NAA both in AD and MCI. Correlating proteomic data from human plasma with neuroimaging is a novel approach to both early diagnosis as well as monitoring disease progression in AD.

0799 Reduced Extrapyrainidal Symptoms And Tardive Dystdnesia In Patients With Dementia Receiving Low-Dose Risperidone Compared To Low- Dose Haloperidoh A Systematic Review

Boundy, K l, Woodward, M 2, Alnes, D ~, Aldridge, G 4, Brodaty, H ~, Byrue, G 6, Snowdon, jT, and Hertel js. 2University of Adelaide, Adelaide, Australia; 2Austin Repatriation Campus, Melbourne, Australia; 3University of Mdbourne, Melbourne, Australia; 4M-Tag Pry Ltd, Sydney, Australia; 5University of New South Wales, Sydney, Australia; ~University of Queensland, Brisbane, Australia; ZRozelle Hospital, Sydney, Australia; SJanssen-Cilag Pry Ltd, Sydney, Australia.

Background: The purpose of tiffs literature review was to compare reports of ExtrapyramJdal Symptoms (EPS) and Tardive Dyskinesia (TD) in patients with dementia treated with low-dose risperidone and low-dose haloperidol for behavioural disturbances of dementia. Method: A systematic review of published English literature up to June 2004 was conducted. Only studies with a dose range recommended for behavioural disturbances of dementia, up to 1 mg twice daily, were included. Studies were excluded if the majority of patients investigated had schizophrenia and mood disorders, or if patients had TD at baseline. For EPS, studies included patients without EPS at baseline or those reporting treatment-emergent EPS. Results: A total of 1623 citations were identified and 38 were included. Although tolerability was also assessed in tiffs review, other adverse events were not well reported and therefore will not be presented. A significant reduction in severity of EPS in favour of risperidone versus haloperidol was reported (Simpson Angus Scale mean difference: 4.0; Extrapyranffdal Symptoms Rating Scale total, mean difference: 1.9). The incidence of EPS was also sigtffficantly lower with risperidone compared to haloperidol (risk difference -- 9%; 95% C1-16.7, -1.3). For TD, a lower incidence of TD for risperidone (5%) compared with haloperidol (32%) was reported (relative risk - 4.12; 95% C~ 2.52, 5.75). Conclusion: There was a reduction in movement-related disorders (EPS and TD) with risperidone compared to haloperidol in patients with dementia, suggesting that the use of risperidone may be preferred over haloperidol for the treatment of behavioural disturbances of dementia.

0800 Hydrocephalie Ideomotor Apraxia

Tsao, jLz,3, Efros, D 2, Knight, A ~, Jeong, y2,3, Fitzgerald, D 2'3, Heilman, K 2'3. 1Uniformed Services University of the Health Sciences, Bethesda, MD, USA; 2The University of Florida College of Medicine, Gainesville, FL, USA; 3Department of Veterans Affairs Medical Center, Gainesville, FL, USA

Background: Although corpus callosum (CC) thinning is often associated with normal pressure hydrocephalus (NPH), signs of discomlection such as ideomotor apraxia (IMA) of tile left forelimb have not been described. Method: Two fight-handed women (ages 82 and 64) with normal Mini-Mental Status Exanffnation (MMSE) scores and language (e.g., Boston Naming Test), underwent left- versus right-hand testing for agraphesthesia, astereoagnosis and aprmxia (transitive pantomimes to command and imitation), compared to age- and sex-matched controls. Results: In the first subject, both hands were equally agraphesthetic, but she performed worse with her left (27% correct) than right hand (50% correct) when tested for astereoagnosis. She correctly performed 27% transitive pantomimes with the left hand, but 47% with the right, and 73% imitative pantomimes with her left hand were correct compared to 55% with the right. In the second subject graphesthesia was equal for both hands, but with stereoagnosis, she performed worse with her left (50% correct) than right (90% correct) hand. She also demonstrated an asymmetrical IMA with command (42% correct with left hand and 60% correct with right hand) and imitation (0% correct with left hand and 82% correct with right hand). Normal subjects denlonstrated 50% and 45% accuracy in both hands to command and imitation, respectively. Brain MRI was consistent with NPH in both subjects, with tlffnrdng of the CC body to 2.7 nm~ and 2.1 nm~, respectively (normal: 5.0 6.2 mm). Conelnsion: The presence of asymmetric (left-sided) IMA and impaired tactile narning, consistent with functional callosal disconnection, appear to accompany NPH.

0801 Tile Clitlical SignitieanCe of White Matter Changes and Hippocampal Atrophy and of Hypoperfusion on 3D-SSP in Alzheimers Disease

Tsujthata M, Nakao Y, Tomita I, Honda H, Iwanaga K, Satoh A, Satoh H, Seto M, Oclff M. Neurology Section, Nagasa]ci 2~'ta Hospital

Objectives: We evaluated the clirdcal significance of white matter changes and tffppocampal atrophy on MRI, and hypoperfusion on 3D-SSP in patients with probable Alzheimer's disease (AD). Methods: 145 AD patients (age 76.5 -c 7.9 years), 43 MCI patients (172.6 ± 7.0), and 100 controls (167.5 ± 8.1). The subcortical and deep wlffte matter hyperintensities (DSWMH), periventricular hyperintensities (PVH), and etat cribles, including lacunar infarcts in the basal ganglia, on MRI were assessed using the rating scale of the Japanese Society for Detection of Asymptomatic Brain; GO to G3, GO to G4, GO to G3, respectively. Hippocampal atrophy was visually classified into 4 grades; GO to G3. SPECT was obtained in 105 AD, 34 MCI and 35 controls. Z-scores of over 3 on 3D-SSP in the parietal- temporal surface and/or precunei to the posterior cingulated gyri were judged to indicate abnormal hypoperfusion. Results: The degree of DSWMH, PVH and etat cribles was related to the age of the controls. The frequencies of these changes did not differ between the MCI and controls, but they were more frequent in AD. The frequency of moderate (G2) and marked (G3) lffppocanlpal atrophy in the AD, MCI and control was 33.1%, 11.6"/o and 0%, respectively. The frequency of hypoperfusion on 3D-SSP in the AD, MCI and controls was 57.1%, 44.1% and 0%, respectively. Conclusion: The detection of hypoperfusion on 3D-SSP was superior to that of hippocampal atrophy when diagnosing AD. The identification of hypoperfusion on MCI may suggest either subclincal or early stage of AD.

0802 Why Dementia Progress Non-linearly?

Vysata, O l, Pazdera, L ~. 1Neurocentre Caregroup, Rychnov nod Kneznou, Czech rep.

Background: For tire patients with Alzheimer's disease, the cognitive deterioration is slow during the early and late stages and more rapid

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during the middle stages. Only degree of cognitive impairment and previous rate of cognitive decline predict rate of deterioration. The relation between rate of change and severity might be due to the specific composition of the testing scales. Nevertheless it probably reflects correlation of neuropathologic and symptomatic change in Alzheimer disease, because measurement with different scale types gives similar results. Method: The simulations of dementia progression on different types of neural networks were used. Results: Several possible sources for non-linear progression of dementia were found. 1. Non-linear decline of the number of neurons. 2. Non-linear dependency of the synapses number on the linear decline of the number of neurons (for some network architectures). 3. Neural network tolerance to damage (In our model the network forgot the first pattern after removing more than 60% connections between neurons). 4. Non-linear transfer fmlction. Conclusion: Non-linear progression of dementia reflects probably fundamental properties of the neural networks.

0803 Transient Global Amnesia Associated with Mild Cognitive Impairment: Magnetic Resonance Spectroscopy Correlation

Wong HCE l, Chan YL 2, Dai DLK: . Affiliations: 1Department of Medicine and Therapeutics, Prince of Wales Hospital, Hong Kong SA R; 2Department of Diagnostic Radiology and Organ Imaging, Prince of Wales Hospital, Hong Kong SAR

Background: The etiology of transient global amnesia (TGA) has been attributed to vascular insufficiency, venous congestion and migraine. Most of these patients recover completely but cognitive impairment has been shown in a small number of patients in long-term follow-up. Method: Review a case with TGA who later developed mild cognitive impairment. Results: A 74-years old Chinese lady with atrial fibrillation, hyperten- sion, gout and diverticular disease presented 3 years ago with two episodes of TGA separated by 14 months. Both episodes fulfilled Caplan's modified criteria for TGA. She did not have any memory or cognitive complaints in between these episodes. Electroencephalogra- phy was normal. Computed tomography of her brain showed age- related atrophic changes. Magnetic resonance (MR) imaging showed no cerebral infarct and there was no intracranial arterial stenosis seen on M R angiogra4Jtry. M R spectroscopy (MRS) of the posterior cingulate gyrus showed normal N-acetyl-aspartate (NAA) peak, decreased choline peak and increased myoinosital peak consistent with early Alzheimer's disease. She remained functionally well in subsequent follow-up but complained of forgetfulness 18 months after the second TGA episode. She received no formal education and her mini mental state examination score was 28/30. Clinical dementia rating was 0.5 and the cognitive subscale of the Alzheimer's Disease Assessment Scale score was 16/85. She fulfilled the diagnostic criteria of mild cognitive impairment (MCI). Her cognitive status has remained stable at her most recent follow-up. Conclusion: TGA may predate the develotnnent of cognitive impair- merit. M R spectroscopy may be used to identify at-risk patients and facilitate early treatment.

0804 PRION-1 TRIAL: Therapies For Human Priori Disease (ISRCTN06722585)

Wroe, S ~, Thomas, D ~, Rossor, M 3, Walker, A 4, Keogh, 04'5, Siddique, D ~, Webb, T ~, Pal, S ~, Darbyshire, j4, Collinge, js. 1National Priori Clinic, London, UR," 2Department. of Neurology, St Mary's Hospital, London, UK; 3Dementia Research Group, Institute of Neurology, London, UK; 4MRC Clinical Trials Unit, London, UK; 5MRC Prion Unit, London, UK

Given the progressive course of human prion disease, and no proven therapeutic options, there is an understandable desire on the part of patients and their families to access treatments with even limited evidence of efficacy. The UK Medical Research Council has established a fi'amework for the clinical assessment of therapeutic options, PRION-1, that can be refined or expanded as new agents become available. PRION-I is initially evaluating qninacrine (mepa- trine hydrochloride) which penetrates the CNS when taken orally and has a well documented toxicity profile. The rationale for its use is based on experimental data using mouse-adapted scrapie priori strains in infected cell cultures.

PRION-1 is a partially randornised patient preference trial to evaluate the safety and efficacy of qninacrine in all types of human priori disease. Patients are placed into one of 3 groups according to pre- ference: 1) randomised controlled comparison ofinm~ediate open-label qninacrine versus quinacrine deferred for 24 weeks, 2) non-randomised assessnlent of inmtediate open-label qninacrine or 3) follow-up without quinacrine treatment. All groups follow the same schedule of evaluations. The primary objective is to evaluate mortality and the proportion of "responders'" and "non-responders'" in all three cohorts based on video of neurological examination, CIBrC-plus and BPRS. Secondary objectives are to evaluate neurological and neuropsycho- logical changes, and to evaluate toxicity and tolerability of qninacrine. It is intended to expand the follow-up aml into a longitudinal prospective systematic cohort of all UK patients diagnosed with human priori disease.

0805 MRI Studies on primary progressive aphasia: a case analysis

Ymnei, Z, Yongjun, W, Yflong, W, Yue, H. Department Of Neurology, Beijing Tiantan Hospital Prince of Wales Medical Research Institute

Backgroud: To reveral where primary progressive phasia patient brain damaged, what the changes of blood flow, metabolism and connection fibers on brain by inducing the imaging characteristic of a primary progressive aphasia. Methods: Used 3.0T SIEMENS Trio 2003T and AG 2003 work station- siemens to scanning, data analyzed and imaging post processing: (1) conventionality MRI. Results; (2) magnetic, resonance spectroscopy; (13) perfusion weighted imaging; (14) diffusion tensor imaging. Results: Conventionality MRI demonstrated atrophy of left temporal lobe and fi'ontal lobe, especially left temporal pole, functional magnetic, imaging showed left frontal lobe and temporal lobe metabolism decreased, and left pole temporal and foreside of frontal lobe blood flow reduced; FA value and seeds tracing lacertus of left corticospinal tracts were reduced than that of contralateral side and the nmnber of fibers between Wemicke's and Broca's area were decreased than that o f contralateral side. Conelnsion: Major diseased regions of primary progressive phasia is located at left temporal or frontal lobe, where hypoperfusion and hypometabolism than that of contralateral side and the number of fibers between Wernicke's and Broca's area were decreased, such tlfings may be the pathologic mechanisms of aphasia.

0806 Tile hnportanee of tile detection of proviral load in PBMNC and CSF in the dilterential diagnosis between H A M / T S P and multiple sclerosis

Puccioni-Sohler M, L2's Yamano y,4 Gon~alves RG, ~.~ Vasconcelos CCF, ~ Papals-Alvarenga R, * Jacobson S 4. 2Neurological Department, ( HUGG/ EMC/ UNIRIO ) , R J, Brazil," 2 CSF Laboratory, Clinical Pathology" Service, (HUCFF/UFR)'), RJ,Brazil; 3CSF Laboratory" (NeuroFfe), -P-J, Brazil; 4NINDS, National Institute of Health (NIH), Bethesda, MD