Poster Abstracts Wednesday, November 9, 2005 $297

Conclusion: The profile o f memory impairments is different in patients with AD, DLB and PB and may be useful in differential diagnosis of dementia.

0772 Relationship between visuospatial and visuoeonslructive hnpaixments and visual halludnation in dementia with Lewy bodies, Alzheimer's disease and Parkinson's disease

Petrovie, M ~ , Zlatic, G a , Ocic, G ~, Savic, A ~, Tomic, G ~, Knezevic, Z ~, Toncev, G 1. 1Center for Neurology, Clinical Center Kragujevac, Kragujevac, Serbia & Monwnegro; 2Institute of Neurology, Clinical Center of Serbia, Belgrade, Serbia & Montenegro

Introduction: The aim of this study was to investigate relationship between visuospatial and visuoconstructive impairment and visual hallucination in patients with dementia with Lewy body (DLB), Alzheimer's disease (AD) and Parkinson's disease (PD). Methods: Twenty-three demented patients (8 DLB patients and 15 AD patients), 10 patients with Parkinson's disease (PD) and 10 healthy subjects were analysed. All groups were matched with age (lover 65 years), educated level (eight years) and time of the beginning of the disorders (over two years). Tire baseline neuropsychological profile was examined by the global score (Mini Mental State Examination). Subscores of the visuospatial and visuoconstructive impairment were compared by Matfis Dementia Rating Scale. All types of hallucina- tions were analyzed by BEHAVE-AD test. Results: Patients with DLB were found to have significantly higher visuoconstructive and visuospatial impairment vs. AD patients (p - 0.041), and vs. PD patients (p -- 0.046). AD patients were also found to have significantly higher visuoconstructive and visuospatial impair- ment vs. PD patients (p -- 0.012; p < 0.05). DLB patients were found to have significantly more visual hallucinations vs. AD (p -- 0.001, p < 0.01) and vs. PD (p -- 0.014, p < 0.05). AD patients were found to have significantly more visual hallucinations vs. PD (p - 0.000, p < 0.01). There were no differences between the other types of tire hallucinations. Conclusion: Visuospatial and visuoc.onstructive impairment and visual hallucination examination could help in differential diagnosis between DLB, AD and PD with dementia.

0773 Does tile presence of pshnomental retlex help predict MCI comse?

Pfeffer, A, Gabryelewicz, T, Barczak, A, l~uczywek, E, Wasiak, B, Bardkowska, M. Department Of Neurodegenerative Disorders Of Medical Research Centre Of The Polish Academy Of Science/CSK MSIViA

Background: Individuals with mild cognitive impairment (MCD have a high risk to develop dementia. A large number of variables appeared to be predictors of dementia in subjects with MCI. Palmomental reflex (PMR) is more commonly found in demented patients than in age- matched healthy controls. Pedraps its presence can be taken into account as accessory marker to identify subjects with dementia at follow up from among subjects with stable MCI. Objective: To test the hypothesis, that P M R is overpresented in MCI subjects who developed dmically diagnosed dementia, when compared with stable MCI. Material and Methods: The subjects of this study were 102 patients with MCI diagnosed according to the criteria proposed by Petersen et al. (11997). Presence of palmomental reflex was evaluated at all. After 2 years follow up, all patients were divided into 3 groups: 1-42 subjects with stable MCI course, II-43 subjects with progressive symptoms of cognitive impairment, but who did not meet clinical criteria for dementia, III-17 subjects, who converted to dementia. Frequency of presence of P M R at the initial visit was compared between these three groups.

Results: P M R was present significantly more frequent in group II (153 %) and in group III (152.5 %) than in group I (126.2%). Chi2 -- 7.466, p -- 0.024. Conclusion: Presence of palmomental reflex is associated with increased risk of progressing course of cognitive impairment in our group of MCI patients.

0774 Deulenfia and plasma levels of Ab40 and Ab42 in patients with Down syndrome

Pixttilii, T, Frey, H, Heikkilfi, L, Kivimfiki, T, Wegiel, J. 1Dept Of Neurology, University Of Kuopio, Finland," 2The Joint/vlunicipal Authority for Social Services in Pirkanmaa, Finland," 3New York State Institute for Basic Research in Developmental Disabilities, New York, U.S.A.

Baekg*ound: The levels of A[342 in plasma are elevated in patients with mutations in APP and presenilin genes before clinical symptoms as well as in patients with mild cognitive impairment who develop Alzheimer's disease (AD). Patients with Down syndrome (DS) develop AD neuropathology by the time they reach 40 years of age. Our aim was to exanfine the relationship between plasma AIM0 and A[342 levels and development of dementia in patients with DS. Method: Fourty adult DS patients (126-64 years at baseline) were followed for five years. Nine patients were demented at baseline and eight patients became demented during the follow-up. Plasma A[340 was measured by a home-made sandwich ELISA and A[342 was measured by a commercially available sandwich ELISA kit (Imroge- netics, Belgimn). Results: Plasnra levels o f A[342 and A[340 were higher in DS patients than non-DS individuals. The levels remained stable in individual patients during the follow-up. There was no association between the development of dementia and plasma levels of A[340 or A[342 at baseline or during the follow-up. Conclusion: Plasma A[340 and A[342 levels are increased in DS but are not associated with development of dementia.

0775 Tile combination of CSF Ab42 and Tau or Phospho-Tau predict progression in patients with mild cognitive hnpainnent

Pixttilii, T, Herukka, S, Hallikainen, M, Soininen, H. Deparment of Neurology, University Of Kuopio

Background: Patients with mild cognitive impairment (MC 0 have an increased risk of developing dementia, particularly Alzheimer's disease (AD). However, tire etiology of the MCI is heterogeneous and some patients may never develop dementia. The aim of this study was to study CSF A[342, Tan and pTau as predictive biomarkers of AD after an extended Follow up in a hospital cohort of MCI patients. Method: The study population consisted of 108 patients (146 controls, mean age 67.4 years and 78 MCI patients, mean age 70.4 years) who were referred to the memory clinic Kuopio University Hospital or participated in an ongoing longitudinal population based study. The CSF levels of A[342, total Tau and pTau0a~, ) were measured by a commercial enzyme-linked im_munosorbent assay, ELISA (inno- genetics, Ghent, Belgiunr). Results: After the mean follow up of three years (0.5-12 years), 55 MCI patients remained stable (stable MCI) and 23 patients progressed to AD (progressive MCI). The CSF A[342, total Tau and pTau values were not significantly different between the control group and the stable MCI group. Increased Tau and pTau levels showed high sensitivity (187°'; for both) whereas decreased A[342 was tire most specific (174.5°,5) in discriminating progressive MCI. The best positive LR (4.00) was found for the combination of AIM2 and pTau.

$298 Wednesday, November 9, 2005 Poster Abstracts

Conclusion: CSF biomarkers help to detect MCI patients who develop AD.

0776 Evolution of clinical li~atmes in Dementia with Lewy-body timing long-term follow-up

Pradhan, S. Sanjay Gandhi Postgraduate Institute of Medical Sciences, Luclrnow, India.

Background: Evolution of clinical features in late stages of Dementia with Lewy-body (DLB) is not clearly known. Methods: Seven patients with features suggestive of DLB (coguitive impairment, parkinsonian features, visual hallucinations and marked fluctuation in symptoms) are described for atypical presentation during the long-term follow-up. These patients were examined at four- monthly intervals for 3-5 years and any change or development of new symptom or sign was noted. M R imaging of the brain was performed at 1-2 yr intervals. Results: After 6-18 months, marked swing in behavior from highly agitated state to a transient depressive state was noted in 5 patients; rest of the 2 had persistent psychosis. Treatment with anti-psychotic drugs was frustrating due to rapid development of extra-pyramidal syndrome. MRI showed generalized but predominantly parieto- occipital atrophy. Between 2-3 years of illness, 6 patients showed postural instability with tendency to fall forward (4 patients) or backwards (2 patients) and vertical gaze paralysis simulating PSP. Mid- brain collicular atrophy was also noted on MRI at this stage in 5 of them. Four patients were walking independently between 3-4 years and two of them had difficulty in walking tandem and limb ataxia. MRI showed additional atrophy of olives, vetmis and cerebellar hemispheres. Drop in blood pressure on standing with symptoms of postural hypotension were observed in 3 patients with 3-5 years of illness. Conclusion: Natural course of DLB needs more studies as our patients in advanced stage of the disease showed cliuical and MRI features, which may be confused with PSP or MSA.

0777 S100A9, an Inflammation-Associated Calcium-Binding Protein, Is a Binding Partner for Various Redox-Regulating Proteins in Familial Al.zheilner's Disease

Ratlimi, F x, Goyette, j2, Raftery, M 2, Shepherd, C 1, Halliday, G 1, Geczy, C 2. Z Prince of Wales Medical Research Institute and; 2 University of New South Wales, Sydney, Australia

Background: Inflammation, oxidative stress and genetic, predisposition are pathogenic factors contributing to neurodegenerative diseases including Alzheimer's disease (AD), but neuroinflammatory processes in fanfilial presenilin-1 (PS-1) AD differ from sporadic AD (S-AD). S100A9 is an inflanunation-associated protein that may regulate redox function, as suggested for S 100B. Methods: Immunohistochemistry and Western blotting assessed S100A9 expression in control and AD samples. Control, S-AD and PS-1 AD brain extracts adsorbed with anti-S100A9-inmmnoaffinity were eluted with EGTA to identify potential CaZ+-binding part- ners that were separated by SDS-PAGE and processed by mass spectrometry. Results: Like S100B, SI00A9 was consistently co-localized within neuropathological hallmarks of AD brain; soluble S100A9 was siguificantly increased in PS-1 AD. Argininase and superoxide dismutase were identified in PS-1 and S-AD extracts. Of the 7 PS-1- specific proteins, 4 can regulate redox and/or apoptosis. Caffiepsin D, which cleaves amyloid precursor protein to amyloidogenic compo- nents, was also ehited. Conclusion: The earlier onset and rapid disease progression observed in PS-1 AD cases may involve S100A9-modulated inflanmmtory and redox pathways. Further analyses and characterization of some of these are necessary.

0778 Safety of Galantanfine and Memantine in Combination Usage in the Treatment of Mild to Moderate AIzhehner's Disease

Ramaswamy, K1; Amatuiek, j2; Zhu, y2.2Jansse n Medical Aft'airs L.L.C., Titusville, New Jersey, USA; 20rtho-McNeil Neurologics, Inc., Titusville, New Jersey, USA

Background: There are no published data on the safety and tolerability of the concomitant use of galantarnine and memantine in Alzheimer's disease (AD) patients. A preliminary interim safety analysis o f an ongoing observational study of patients with mild-to-moderate AD was performed. Methods: Included in this 2-year, multi-center, prospective, open-label, observational study are patients who at entry were either receiving treatment with galantanfine (GAL) or no medication indicated for AD (untreated). Tire naturalistic design permits physicians to alter therapy as needed. Study data collected at the time of the first interim observed case (OC) analysis included patients who received memantine (MEM) as well as other treatments. Because of uneven follow-up times, the analyses were adjusted for years at risk. Results: A total of 429 subjects were analyzed in one or more groups: GAL (319), MEM (9), GAL plus MEM (148), AChEI other than GAL (other-AchEI, 18), and untreated (114). Adverse event (AE) data were compiled for a total of 259.9 patient-years at risk (y) (GAL, 158.9; MEM, 1.7; GAL-MEM 24.5; other AChEI, 4.5; untreated, 70.3). A total of 19.3% patients reported AEs (10.32 Per Year at Risk [PYR]). AEs were reported by 14.1% (10.28 PYR) of GAL, 16.7% (0.33) of GAL-MEM and by 19.1% (0.38) of untreated subjects. Furthermore, AEs were reported by 22.2"/0 (1.18) and 5.6% (10.22) of MEM and other-AChEI treated subjects, respectively. Conclusion: Preliminary data analysis suggest that GAL-MEM use may be safe and well tolerated compared to no AD treatment, in a mild to moderate AD population.

0779 CSF Tau and Amyloid J~I-42 (AJ}42) as possible Biomarkers of Alzhehner disease

Ravid, R l, Kanrphorst, W. /Tw Netherland~ Brain Bank, Amsterdam, The Netherlands

The diagnosis of neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD) is severly hampered by the absence of suitable biomarkers that can be measured in body fluids such as blood and cerebrospinal fluid (CSF). These markers can explain the pathological mechanisms underlying the various diseases and have a predictive value in early diagnostics. Bio Banks are an essential repository for post-mortem specimens and body fluids The biomarkers identified in blood and CSF may reflect fluc- tuation in processes; they also indicate the formation of the extra- cellular amyloid-containing senile plaques (SP's) and intracelhilar neurofihiillar tangles (NFT's) consisting of (hyperphosphorylated) tau-proteins. It has been shown that ante-mortem CSF Amyloid [~-4~ (A[~42) is significantly decreased in AD. CSF tau, and more specifically its hyperphosphorylated forms (p-tau) is significantly higher in AD patients as compared to non-dementing age-matched controls.

Biomarkers reflect the processes that underly the pathological hallmarks of the disease. However, the defiuite and accurate diagnosis can only be validated at post-mortem autopsy.

In the coming decenia brain banks will collect, preserve and type RNA and DNA extracted from brain specimens in order to update the pathological hallmarks of AD and PD.

In the present study we show that biobanking is vital to assess the validity of ante-mortem and post-mortem CSF A[~42 and P-tau in reflecting tire hallmarks of AD to support the development of reliable early diagnostic procedures.