$300 Wednesday, November 9, 2005 Poster Abstracts

Background: Cognitive impairments are associated with long term cannabis use and the consequences of intellectual impairment are far reaching for young people in their most productive years. Impairment appear to increase with duration and fiequency of cannabis use; however, the attribution of deficits to lingering acute effects, drug residues, abstinence effects, or lasting changes caused by chrorfic use continues to be debated. This study investigated the effects of duration of cannabis on specific, areas of cognitive functioning among Nigerian young adults. Methods: Tiffs study compared 92 near-daily cannabis users on the Conmmnity Screening Instrument for Dementia with 92 nonuser controls. There were 41 long-term cannabis users: mean of 15.3 years of regular use, 41 shorter-term cannabis users with a mean of 7.2 years of regular use and nonusers of cannabis. Confounding variables such as age, educational attainment were controlled through matching. Tobacco, other psychostimulant and alcohol use was minimal. Participants abstained for at least 12 hours prior to testing. Resnits: Long-term cannabis users performed significantly less well than shorter-term users and controls on tests of memory, attention and calculation and prmxis. There was an inverse relationship between duration of cannabis use and total Conmmnity Screening Instrmnent for Dementia scores (r -- 0.32;p < 0.01) after controlling for age and educational attairm~ent. Conclusion: These results show clearly that Nigerian long-temt heavy cannabis users show impairments in memory, attention and calculation and prm, ds when they were not intoxicated and worsen with increasing years of use.

0785 Cognitive deficits and their relationship to other neurological complications in Nigerian chronic alcoholic patients

Salawu, F, Bwala, S, Wakil, M, Rabebe, I, Waru, G, Bukbuk, D, Nyandaiti, Y, KJda, I. Federal Medical Centre, Nguru. Yobe State. Nigeria University of Maiduguri, Maiduguri. Borno State. Nigeria Federal Neuropsyehiawy Hospital, Maiduguri.Borno State. Nigeria University of Maiduguri Teaching Hospital, Maiduguri. Borno State. Nigeria

Background: Alcohol related problems have become an increasing cause of concern in Nigeria. This study describes the prevalence and the clinical importance of alcohol-induced brain damage, evaluated by neuropsycholo gical tests and correlated with peripheral and autonomic nerve damage, and with liver function. Methods: Seventy chronic alcoholics were randomly selected from a conmmnity in North east Nigeria and matched for age and sex with 70 randomly selected non-drinking controls from the general population. Liver damage was confirmed by ultrasound scan and haematological parameters. Patients suspected to have hepatic, encephalopathy or Wen-ficke's encephalopathy were excluded from the study. Peripheral neuropathy was taken as the presence of two or more abnormal findings on peripheral nervous system exanffnation, while autonomic neuropathy was diagnosed when at least one of these was abnormal; postural blood pressure changes, handgrip test, changes in heart rate during Valsalva manoeuvre and deep breath testing. These and administration of Community Screening Instrument for Dementia were performed one to two weeks after alcohol withdrawal. Results: Cognitive performance of the group of alcoholic patients was sigrfificantly lower than those of the control group. A high prevalence 64.3% of cognitive deficits was found. Peripheral neuropathy was seen in 71.4%, autonomic neuronal damage in 21.4%.Cognitive deficits were not correlated with age, daily ethanol intake, and duration of alcohol abuse or severity of liver damage. There was no correlation of peripheral, autonomic and central nervous system damage. Conclusion: Alcohol-induced damage of the nervous system is a corma~on complication of chrorfic alcoholism, whose clinical impor- tance often obscures possible concomitant liver damage.

0786 Effect of galantamine on cognition based on lesion location in patients with Ahhehner 's disease plus cerebrovascular disease or probable vascular dementia

Salloway, S, 1 Brashear, HR, 2 Zhu, y3. ~Butier Hospital, Brown Medical School, Providence, Rhode Island, USA; 2Johnson & Johnson Pharmaceutical Research and Development, L.L.C., Titusville, New Jersey, USA; 30rtho-MeNeil Neurologies Inc., Titusville, New ,fersey, USA

Background: A combination of A D + C V D may be involved in many cases of dementia. Galantamine, an acetylcholniesterase inhibitor and allosteric modulator of nicotinic receptors, has shown cognitive benefits in probable AD, possible AD with significant CVD, and probable VaD. Methods: During a 6-month, double-blind, randomized trial, patients with possible AD (NINCDS-ARDA criteria) plus radiologic evidence of CVD or probable VaD (NINDS-AIREN criteria) were treated with galantamine (up to 24 rag/d) or placebo. In this post-hoe analysis, we evaluate effect o f galantamine on cognition measured by ADAS- cog/ l l , by territorial (TL) (multiple infarcts or single strategic infarcts) or subcortical lesions [white matter lesions (WML) or lacunar infarcts (LD]. Results: Of 592 patients randomized, 264 had subcortical lesions ("pure" -- 120) while 78 had territorial infarcts ("pure "> - 32) in the AD+CVD group. 200 VaD patients had subcortical lesions, ("pure" - 53) while 106 had territorial infarcts ("pure" -- 46). At 6 months, galantanffne-treated patients with any TI, LI or WML demonstrated cognitive benefits verses placebo Qv < 0.05, p < 0.01, p < 0.001 respectively) galantamine-treated patients with "pure" subcortical lesions experienced significant improvement verses placebo (i-0.75 vs 1.52; p -- 0.019). Differences were significant in AD+CVD-related "pure" subcorfical lesions Qv - 0.039). No sigtffficant treatment-group difference was observed for "pure" TL (p - 0.164; AD+CVD, p - 0.515; and VaD, p - 0.343). Conclusions: Among patients with any subcortical lesions and who completed the study, those treated with galantamnie experienced significantly greater cognitive benefits than placebo. Among comple- ters, galantamine-treated patients with territorial infarcts had signifi- cantly better scores than placebo, however, failure to identify treatment-effects in "pure" territorial lesions may be due to small subgroup sample size.

0787 Alzhehner Disease Associated with Monoclonal Gammapathy

~arac H, Henigsberg N, Petravi6 D 1, Simi6 G. Croatian Institute for Brain Research, Diagnostic Center <<Neuron>>, School of Medicine, University of Zagreb, Zagreb, Croatia. ZUniversity Department of Neurology, School of Medicine, University of Zagreb, Zagreb, Croatia

Introduction: Alzheimer disease (AD) and monoclonal gammapathy (MG) are amyloidosis with unknown joint incidence and pathogenesis. Beta-amyloid is noninnnunoglobulin protein derived from amyloid precursor protein (APP). Aznyloid light chain is product of circulating immunoglobulin precursor produced by plasma cells. Aznyloid pathogenesis and variable amyloid vessel and tissue tropism is not dear. Materials and methods: Two patients with joint involvement of AD and MG are described. The investigation included mini-menthol-state examination (MMSE), CT, MRI, SPECT, tau-231 in CSF, electro- phoresis, immunoelectrophoresis and sternal biopsy. Results: Joint involvement of AD and M G was noted simultaneously. The diagnosis of AD is based upon MMSE, CT, MRI, SPECT, tau-231 protein in CSF. Patho gnomonic narrow banded electrophore- tic peacks of monoclonal IgG and free light chains of the same kappa type in the serum of both patients confirmed MG. Sternal biopsy show plasma cell dyscrasia as multiple myeloma in patient two who also had

Poster Abstracts Wednesday, November 9, 2005 $301

rheumatoid arthritis. The monoclonal gammapathy of undetermined significance was verified in patient one who had serious aortal stenosis, too. Conclusion: Monoclonal ganmlapathy in both patients was coincident finding, but occurence of paraproteinaemJa in AD is probably more than chance association and it should be searched for in patients presenting with AD and/or in mild cognitive impairment (MCI) patients. These findings could actuate more experiments on circulating monoclonal protein and APP based upon hypothesis that AD is not solely localised amyloidosis but it also could be involved in sistemic inmmnological disease.

0788 Effect of Galantamine on Cognition in Subjects in MRI Subgroups With Vascular Dementia: Impact of Lesion Type on ADAS-cog/11 and EXIT- 25 Scores

Scheltens P~, Gassmann-Mayer C 2, Brashear B 2, Van Straaten ECW ~, Barkhof F 1. 2Dept. Neurology/Alzheimer Center, VU University Medical Cotter University, Amsterdam, Netherlands.." 2Johnson & Johnson Pharmaceutiea! Research & Developmozt, Titusville, New Jersey, USA

Baekgrouml: Data previously presented showed significant overall ADAS-cog/11 improvements between galantanffne (GAL) and placebo (PBO) (mean change: -1.5; P < .001). The current analysis compared GAL with PBO in MRI-defined subpopulat ions of subjects with VaD stratified by lesion type. Methods: Subjects with VaD (based on N I N D S - A I R E N criteria) were randomized to receive G A L 16 or 24 mg in a bid regimen or PBO in a 26-week, double-blind, flexible-dose trial. Outcome measures included the ADAS-cog/I 1 (GAL, n - 364; PBO, n -- 372) and EXIT-25 (GAL, n - - I I 6 ;PBO, n - - 116). Results: At week 26 (LOCI;.), significant ADAS-cog / l l score improvements were reflected between groups in subjects with multiple lacunar infarcts (MLI; 2.0; P - 0.021), extensive white matter disease (WMD; 2.3; P < 0.001), or multiple territorial infarcts ( 2.5; P - 0.046). There was no significant ADAS-cog/11 between-group diffe- rence in subjects with single critical infarcts (SCI; P - 0.628). The between group difference in EXIT-25 showed a numerically higher improvement in favor of GAL: MLI (mean change: 3.6, P - 0.080), W M D ( 0.68, P -- 0.456), and SCI ( 1.5, P - 0.152). For subjects with time since VaD diagnosis of 0.5-1 and > 1 y, G A L treated subjects showed a numerically higher improvement in ADAS-COg/11 compared to PBO. Treatment-emergent adverse events (TEAEs) and serious TEAEs were reported by 76% and 20% of GAL and 71% and 18% of PBO treated subjects, respectively. Conclusion: GA L can be effective in improving cognition in subjects with VaD. Subjects with SCI do not appear to exlffbit a treatment effect; however, this may reflect single-stroke spontaneous improve- ment or lack of cholinergic pathway involvement by single infarcts.

0789 High conversion rate of MCI to deuleniia in a Meinoty ClitliC cohort

Sclmfidtke, K, Hermeneit, S. Neurogeriatrics And Memory Clinic

Introduction: The conversion rate of Mild Cognitive Impaiment (MC 0 to dementia is known to depend on the description and mode of recruitment of the studied patient samples. In order to enrich a cohort of MCI patients with patients who are thought to be at high risk to develop Alzheimer's Disease (AD), we selected a group of MCI patients who were, at baseline, free of any detectable causes of cogni- tive impairment other than presumed preclinical AD. Their further course was followed prospectively. Methods: 120 consecutive patients (age > 55, mean: 76) of our Memory Clinic received the diagnosis of MCI according to established criteria. Results of notmalised memory tests had to be below minus two standard deviations. Patients in whom causes other titan presumed

preclinical AD were thought to be responsible were excluded, i.e. depressive syndrome, vascular lesions or non-AD degenerative disease. Follow-up was performed one to three years later. Additional second and tlffrd follow-up exanffnations were performed in a subset of patients. Evaluation at our clinic included neuropsychological testing, instrumental activity of daily living questiomtaires, assessment of leading subjective cognitive impairments and the Geriatric Depression Scale. Results: 80 of 120 patients were re-examined in our clinic., and in 21, follow-up data were acquired by structured written or telephone interviews with patients ' pr imary care physicians. All patients who developed dementia received neuroimaging. 19 patients were lost to follow-up.

Of 85 who were re-examined within 1 to 2 years following baseline, 38 (45%) had developed dementia (AD in 35), 6 were considered to be borderline between MCI and AD, 29 (134"/o) were still diagnosed as MCI, and 7 had improved or had received a new diagnosis. Of further 16 patients who were re-examined within the following year, 5 became demented (AD) and 5 still had MCI. Discussion: This "enriched" MCI cohort showed a high rate of conversion to AD within two years (45"/0), plus six cases who were considered "borderline". Tiffs finding supports the concept that MCI is essentially preclinical AD, if other detectable pathologies are excluded. In patient samples defined in tiffs manner, remittance of memory disorder and diagnosis of previously undetected causes of cognitive impairment appear to be rare.

0790 Comparison of senun copper and Senlloplasufin level in Alzhehner paifients and healthy control subjects in Kerman City in ]ran

B. Sedighi, M. Shafa, M. Shariafi. Department of Neurology A~afa Hospital, Kerman, It~4N

Alzheimer's disease (AD) is the most common and important degenerative disease o f the brain. The cause o f AD is not known and there are several theories about it i.e. possible role of trace elements as copper and the related oxidative stress. The main transporter of copper; 72 globuline ceruloplasmin, is a muhifunct ional etazyme. Increased brain metal levels have been associated with normal aging and a variety of degenerative disease, including AD. Copper and iron levels both show marked increases with age and may adversely cause production of neurotoxic hydrogen peroxidase (H.202), that is related to AD pathogenesis. Variations in serum copper concen- tration occur because of age, sex, hormonal state, diet and geo- graphical factors and therefore investigation concerning correlation between serum copper level and AD in different populat ions will be reasonable. Regarding tiffs issue in a case/control survey, we studied serum copper and ceruloplasmin levels in 50 patients with AD (mean age 76.4 years, 26 men, 24 women) and 50 cognitively normal individuals (mean age 67.8 years, 25 men, 25 women). We used MMSE questiomtaire to determine and select the patients and the control groups. Other causes of demntia and disturbing factors of copper metabolism were excluded. Copper serum level was measured by calorymetric technique and LKB spectrophotometer and ceruloplasmin serum level by ferro-oxidase technique and LKB spectrophotometer. Results: There is a positive correlation between serum copper level and age (P - 0.018) but in case of serum copper and ceruloplasmin there is no difference between case and control groups. Conclusion: There is no correlation between serum copper and ceruloplasmin level and AD in our geographical area.

0791 A correlation between neuropsyctlologieal test scores and functional activities questionnaire score in mild cognitive impairment