Poster Presentations P4S784

study accounting for the treatment effect size observed in the GAP study.

Conclusions: Early Phase 1 and 2 studies have demonstrated that human

immunoglobulin may have potential in the treatment of mild to moderate

AD. However, these preliminary findings in small groups of subjects will

need to be confirmed in large-scale, multi-center Phase 3 studies. One

study with Gammagard Liquid/Kiovig is currently ongoing and a second

is planned to begin in 2011.

P4-226 GLIAL CELL LINE-DERIVED NEUROTROPHIC

FACTOR IN LITHIUM-TREATED PATIENTS WITH

EARLYALZHEIMER’S DISEASE

Thomas Leyhe1, Ralf Saur2, Christoph Laske2, Thomas Gasser3,

Peter Annas4, Hans Basun4, Guido Straten2, 1University of T€ubingen,University of T€ubingen, Germany; 2Department of Psychiatry, T€ubingen,

Germany; 3Department of Neurology, T€ubingen, Germany; 4AstraZeneca,

S€odert€alje, Sweden, Sweden.

Background: Preclinical and clinical studies gave evidence that lithium

could be useful in the treatment of Alzheimer’s disease (AD). One possible

mechanism of action might be the induction of neurotrophins. Recently, we

found a significant increase of brain-derived neurotrophic factor (BDNF)

serum levels in AD patients treated with lithium and a significant decrease

of ADAS Cog sum scores in comparison to placebo-treated patients. In an-

other previous study we have shown that glial cell line-derived neurotro-

phic factor (GDNF) levels in cerebrospinal fluid (CSF) of patients with

early AD are increased most probably due to an upregulated expression

in CNS as an adaptive process of the impaired brain to enhance neurotro-

phic support at least in early stages of disease. Methods:Here we assessed

the influence of a lithium treatment on GDNF serum and CSF concentra-

tions in a subset of a greater sample recruited for a randomized, single-

blinded, placebo-controlled, parallel-group multicenter 10-week study, in-

vestigating the efficacy of lithium treatment in AD patients. Results: We

found a significant negative correlation of lithium concentration in serum

with GDNF concentration in CSF at the end of treatment and with the dif-

ference of GDNF concentration in CSF before and after treatment. However,

we could not show a difference in GDNF concentrations between the pa-

tients after the treatment with lithium or placebo.Conclusions: The findings

of the present investigation indicate that beneficial effects of the lithium

treatment such as improvement of neurotrophic support by increase of

BDNF might reduce the necessity of enhanced GDNF expression in the

CNS in early AD.

P4-227 DIVERGENCE OF EFFECTANALYSIS (SLOPE

ANALYSIS) IN DISEASE-MODIFYING AD TRIALS

David Li1, Keith Gregg2, Suna Barlas1, 1Pfizer, Collegeville, Pennsylvania,

United States; 2Janssen Alzheimer Immunotherapy Research &

Development, LLC, South San Francisco, California, United States.

Background: Slope analysis has been recommended by certain regula-

tory agencies to support characterization of disease-modifying effect of

an experimental drug. Two issues are to be resolved to conduct a valid

slope analysis: 1) linearity assumption of responses, and 2) missing

data due to dropouts. Methods: A new statistical slope analysis (diver-

gence of effect analysis) will be considered. This approach is to confirm in-

creasing separation of response differences over time between treated and

placebo group. No linearity assumption of response in each group is

needed. Missing data issue can also be addressed via sensitivity analyses.

Clinical trials will be simulated to evaluate the performance of this ap-

proach and other approaches, in characterizing the disease-modifying ef-

fect in AD trials. The pros and cons of different approaches will be

summarized. Results: It is confirmed that the new statistical approach is

free of assumption that the response in each group is linear, and is robust

to missing data mechanism in general. Conclusions: This new statistical

approach of slope analysis (divergence of effect) should be recommended

to use in AD trials.

P4-228 TAILORING OCCUPATIONALTHERAPY TO THE

INDIVIDUAL NEED OF PATIENTS WITH

DEMENTIA IN THE PATIENTS’ HOME SETTINGS:

A PROSPECTIVE MULTI-CENTRE RANDOMIZED,

CONTROLLED TRIAL (ERGODEM)

Kira Marschner1, Luisa Jurjanz2, Antje Gerner2, Thomas Reuster3,

Meyer Shirin4, Thomas Kallert5, Rainer Koch6, Thomas Becker7,

Matthias Schuetzwohl4, Vjera Holthoff8, 1German Centre for

Neurodegenerative Disorders and Division of Old Age Psychiatry and

Cognitive Neuropsychiatry, University Hospital, University of Technology,

Dresden, Germany; 2Department of Psychiatry, Division of Old Age

Psychiatry, University Hospitals, University of Technology, Dresden,

Germany; 3Staedtisches Klinikum Goerlitz gGmbH, Goerlitz, Germany;4Department of Psychiatry, University Hospitals, University of Technology,

Dresden, Germany; 5Parkkrankenhaus, Leipzig, Germany; 6University of

Technology, Dresden, Germany; 7Bezirkskrankenhaus G€unzburg,

Department of Psychiatry, University of Ulm, G€unzburg, Germany;8Department of Psychiatry, Division of Old Age Psychiatry and Cognitive

Neuropsychiatry, University Hospitals, University of Technology and

German Centre for Neurodegenerative Disorders, Dresden, Germany.

Background: Patients suffering from Alzheimer’s disease are in need of

substantial aid to remain in their own homes as long possible. The study

was aimed at investigating the effect of client-centered occupational therapy

delivered at the patients’ homes together with the caregiver. Here we report

the results of the impact of tailored occupational therapy on the patients’ ac-

tivities of daily living (ADL) and cognition and the follow-up evaluation 3

and 6months later.Methods:A total of 160 patients (76.56 7.4 yrs, MMSE

20.86 3.9 points) and their informal caregivers were randomly assigned to

12 sessions of occupational therapy over 6 weeks added to treatment as

usual (TAU) or to TAU only. Assessment and definition of occupational ther-

apy aims were based on the Canadian Occupational Performance Measure

and Canadian Model of Occupational Performance (COPM). Outcomes

for ADL (ADCS-ADL) and cognition (ADAS-Cog) were measured at base-

line, 2 weeks, 3 months and 6 months after end of intervention or corre-

sponding time point in the TAU group. The analyses are based on linear

models with autoregressive covariance structure for correlated measures.

In model I, the design factors treatment group, time point, centre as well

as interactions between the design factors were included. Model II addition-

ally included MMST, age, and gender, model III additionally baseline as-

sessment. The multiple comparisons of means are Tukey adjusted.

Results: Patients were aged 76.5 6 7.4 yrs and showed a MMSE of 20.8

6 3.9 points. Analysis for the intervention effect on ADL revealed a signif-

icant interaction between treatment and time, and a significant treatment ef-

fect (p < .0001) in model III, in which significant differences between the

two groups were found 2 weeks (p ¼ .0039), 3 months (p ¼ .0002) and 6

months after treatment (p ¼ .0011). Analysis of cognitive functioning

showed treatment x time interaction in model I (p ¼ .0213) and II (p ¼.0225) and model III (p¼ .066).Conclusions:Client-centered occupational

therapy tailored to the capabilities of dementia patients and supporting their

families in the patients’ home settings resulted in clinically relevant benefits

in activities of daily living and effects were still observed 6 months after

completing the intervention.

P4-229 EFFECTS OF EXTENDED-RELEASE MEMANTINE

(28 MG/DAY) ON COGNITIVE DOMAINS IN

PATIENTS WITH MODERATE TO SEVERE

ALZHEIMER’S DISEASE: POST HOC ANALYSIS

OFA RANDOMIZED TRIAL

Michael Tocco1, Suzanne Hendrix2, Michael Miller3, Vojislav Pejovic4,

Stephen Graham5, 1Forest Research Institute, Jersey City, New Jersey,

United States; 2Pentara Corporation, Salt Lake City, Utah, United States;3Prescott Medical Communications Group, Chicago, New Jersey, United

States; 4Prescott Medical Communications Group, Chicago, Illinois, United

States; 5Forest Reseach Institute, Jersey Citty, New Jersey, United States.