Oral O3-07: Therapeutics and Therapeutic Strategies S513

10 weeks). Learning and memory were tested in the Morris water maze.

Cerebral blood flow (CBF) response evoked by whisker stimulation was

monitored by laser Doppler flowmetry. Vasomotor responses were evaluated

on isolated pressurized segments of middle cerebral artery using online vid-

eomicroscopy. Amyloid plaques burden and tissue levels of Ab were mea-

sured using Thioflavin-S staining, anti-Ab immunolabelling and ELISA.

Results:B1r appeared increased in APPmice, particularly in the hippocam-

pus, where double immunostaining showed its expression by activated astro-

cytes (GFAP), but not microglia (CD11b), surrounding Ab deposits.

Learning and memory were significantly improved after 5 and 10 weeks

of SSR240612 treatment. These treatments also ameliorated evoked CBF

responses. Both treatments completely rescued dilations to acetylcholine.

In treated wild-type (WT) mice, however, contractions induced by endothe-

lin-1 and NO synthesis inhibition were significantly reduced compared to

untreated WT. BK elicited a biphasic response (contraction followed by

relaxation) in all groups, with a tendency to constrict and dilate more in

APP and treated WT mice, respectively. Finally, soluble Ab1-42 levels

andAb plaque load were significantly reduced in the brain of APPmice after

both treatments.Conclusions: Together, these data support a role of the kal-

likrein-kinin system in the pathogenesis of AD, and suggest that it may rep-

resent a new therapeutic target.

O3-07-03 ALZHEIMER DISEASE COOPERATIVE STUDY

(ADCS) HOME BASED ASSESSMENT: DESIGNING

TRIALS WITH NEW TECHNOLOGY

Mary Sano1, Susan Egelko1, Steven Ferris2, Jeffrey Kaye3, Tamara Hayes4,

James Mundt5, Tracy Reyes5, Michael Donohue6, Chung-Kai Sun7,

Danielle Whitehair8, Karen Stokes8, Paul Aisen8, 1Mount Sindi School of

Medicine, New York, N.Y., United States; 2New York University, New York,

N.Y., United States; 3Oregon Health & Science University, Portland,

Oregon, United States; 4OHSU, Porltand, Oregon, United States;5HealthCare Technology System, Madison, Wisconsin, United States;6UCSD, La Jolla, California, United States; 7UCSD/ADCS, LaJolla,

California, United States; 8ADCS/UCSD, La Jolla, California, United

States.

Background: Clinical trials of prevention of dementia may be enhanced by

developing novel in-homemethods of assessment. The HomeBased Assess-

ment (HBA) study, a multicenter clinical trial, recruited elders randomized

to one of 3 in-home technologies for assessment. Herewe describe study im-

plementation and cohort baseline characteristics. Methods: Non-demented

individuals> 75 years old were recruited and evaluated by in-person assess-

ment, using established cognitive and functional clinical trial outcomes. Par-

ticipants were randomized to one of 3 HBA experimental methodologies:

1) mail-in questionnaire/ live telephone interviews (MIP); 2) automated

telephone with interactive voice recognition (IVR); and 3) internet-based

home Kiosk (KIO). Brief versions of cognitive and non-cognitive outcomes,

as well as assessment of adverse events, were adapted to the 3 methodolo-

gies and administered at baseline and repeatedly over a 4-year period.

“Efficiency” measures were collected to quantify staff resources required

for each methodology. 27 ADCS sites participated. Site staff attended

a 2-day training meeting. In addition to standard coordinating center sup-

port, daily (12 hrs/day) telephone support was available for KIO operations.

Participants were recruited primarily from community locations. Results:

678 individuals signed consent over 21-months; 640 were randomized.

Demographic characteristics were: mean age 81.3 (4.3); years of education

15.6 (2.9); 32% male; and 22% minority (Hispanic or Non-white). Mean

MMSE was 28.8 (1.2) and 20% were categorized as MCI by in-person

assessment. 59 participants discontinued prior to the baseline evaluation

and there were no differences in age, education, gender or screening

MMSE scores compared to those who continued to participate. The dropout

rate after randomization and the time from screening to baselinewere signif-

icantly different among groups (p< .001) with the highest dropout and lon-

gest time to complete baseline associated with the KIO. Training time

(minutes) also differed (p < .001): MIP 25.4 (15.2); IVR 38.5 (20.5); KIO

77.9 (60.9). Additional analyses will compare methodologies on other effi-

ciencymeasures, accuracy of self-reported adverse events and comparability

of performance on brief outcomes to in-person assessments across arms.

Conclusions: This report demonstrates the feasibility of recruiting an

elderly cohort for assessment in their own homes and enumerates resources

needed to complete the enrolment process.

O3-07-04 FACTORS THAT INFLUENCE SURVIVAL IN

ALZHEIMER’S PATIENTS

Susan Rountree1, Wenyaw Chan2, Valory Pavlik1, Eveleen Darby1,

Rachelle Doody1, 1Baylor College of Medicine, Houston, Texas, United

States; 2University of Texas Houston, Houston, Texas, United States.

Background: Treatment with antidementia drugs (cholinesterase inhibitors

and/or memantine) is efficacious but there is concern that use of these drugs

could prolong survival without improving quality of life. This longitudinal

naturalistic studyexaminedmultiple factors that influence survival in a cohort

of Alzheimer’s patients followed over two decades.Methods: Time to death

after symptom onset was determined in 641 probable AD patients estimated

by a physician using a standardized algorithm. Patients were evaluated an-

nually and information was prospectively entered into a longitudinal data-

base. Survival analysis was performed. Baseline variables included age,

sex, race, disease severity, preprogression rate (PPR), years of education,

and medical comorbidities (diabetes, hypertension, hyperlipidemia, coro-

nary disease, cerebrovascular disease). We also utilized a time-dependent

mechanism to assess the impact of changes in the Mini-mental Status

Exam (MMSE), Physical Self Maintenance Scale (PSMS), Persistency In-

dex (PI) or cumulative exposure to antipsychotic and antidementia drugs,

and psychotic symptoms (hallucinations, delusions) on time to death. Re-

sults: The mean (SD) follow-up time after baseline visit to censoring or death

was 9.3 (3.51) years. Median survival time following the onset of symptoms

was 11.3 (CI: 10.4-11.8) years with 352 deaths. Baseline covariates signifi-

cantly associatedwith increased survivalwere younger age (p¼.0016), female

sex (p¼.0001), and a slower PPR (p< .0001) (an easily calculated estimate of

how fast a patient declines cognitively following the onset of symptomswhich

we previously published). In the final model, time-dependent worsening of

functional ability on the PSMS was also significant (hazard ratio¼ 1.1; CI:

1.07-1.11). Baseline disease severity, vascular risk factors and years of educa-

tion did not influence time to death. Time-dependent changes in anti-psychotic

druguse, development of psychotic symptoms, antidementia drug use, and ob-

servedMMSE changewere not predictive.Conclusions: In this large AD co-

hort survival is influenced by age, sex, the calculated rate or trajectory of

cognitive decline before enrollment, and the development of functional dis-

ability during follow-up. Currently available antidementia drugs provide cog-

nitive and functional benefit when use is persistent, but they do not influence

overall survival in Alzheimer’s patients.

O3-07-05 LONG-TERM EFFECTS OFAMULTICOMPONENT

COGNITIVE INTERVENTION IN AMNESTICMILD

COGNITIVE IMPAIRMENT (AMCI)

Verena Buschert1, Ina Giegling1, Wibke Merensky1, Sabrina Jolk1,

Stefan Teipel2, Harald Hampel3, Dan Rujescu1, Katharina Buerger1,1Ludwig-Maximilians-Universit€at M€unchen, Munich, Germany;2University of Rostock, Rostock, Germany; 3Goethe University, Frankfurt,

Germany.

Background: Recent studies and a current randomized controlled trial on

a mutlicomponent cognitive intervention program demonstrated benefits

through cognitive intervention in subjects with mild cognitive impairment

(MCI). However, few studies determined long-term effects with extended

follow-up periods. Moreover, intervention effects on conversion rate of

MCI-subjects into AD are largely unexplored. Methods: In a randomised

controlled trial, we evaluated effects of a 6-month multicomponent cogni-

tive intervention on subjects with amnestic mild cognitive impairment

(aMCI) with follow-up assessments of 12 and 24 months. Main outcome

measures were changes in global cognitive functions (Mini Mental Status

Examination, MMSE, and Alzheimer’s Disease Assessment Scale, ADAS-

cog), secondary outcome measures were changes in specific cognitive and

non-cognitive functions and conversion into AD. Results: Twenty-four

subjects with amnestic MCI were randomly assigned to intervention