Poster Presentations: P1 P293

Background:There is growing interest in early intervention in the cognitive

decline continuum associated with Alzheimer’s disease (AD). This presen-

tation will consider the framework for evaluating therapeutics designed to

delay the early stages of mild cognitive impairment due to AD (MCI-

AD). Several interventional studies have been proposed to enroll subjects

with normal cognition and follow them until they convert to MCI-AD.

This type of study design puts significant requirements on understanding

the benefit/risk characteristics of the therapeutic. In a novel approach to

AD treatment, a phase III study will examine a non-amyloid mechanism

and target the role of synaptic energetics. The study will evaluate the effi-

cacy, safety, and tolerability of low-dose pioglitazone a thiazolidinedione

(TZD) in preventing MCI-AD in subjects at elevated risk, as defined by

a biomarker risk algorithm, for the onset of symptoms in the subsequent

five years. Methods: Preclinical and clinical evidence suggests that TZDs

may be effective for enhancing cognitive function and forestalling cognitive

decline. fMRI studies have explored the pharmacological effects of low-

dose pioglitazone on memory - related hippocampal function in healthy

elderly subjects. New information regarding the TOMM 40 gene and its re-

lation to the age of AD onset enables us to identify subjects at high risk for

developing AD, a prerequisite for a prevention study.Results:Data support-

ing the use of pioglitazone to delay the onset of MCI-AD will be presented.

Pioglitazone has been used for the treatment of type 2 diabetes for over a de-

cade with >22 million years of patient exposure data. Recent nonclinical

and clinical fMRI study data indicate that low dose pioglitazone has a phar-

macologic effect in a central nervous system region of interest. These

changes occur in a resting state and during a memory task that is informative

for establishing the viability of low doses. Conclusions: This phase III

global, multicenter, randomized, double-blind, placebo-controlled, paral-

lel-group study to evaluate the efficacy of low-dose pioglitazone to delay

the onset of MCI-AD represents a unique opportunity to explore a novel

therapeutic intervention in the earliest phase of the AD continuum.

P1-368 RESEARCH TO PRACTICE: THE TTAP METHOD�

A NEW PSYCHOLOGY OFART, BRAIN AND

COGNITION

Linda Levine-Madori1, Trish Bendel2, 1St. Thomas Aquinas, Sparkill, New

York, United States; 2Edward Hospital, Naperville, Illinois, United States.

Contact e-mail: Llevinem@stac.edu

Background: This session will define the neuroscience discoveries over the

past decade regarding cognitive reserve theory and the TTAP Method �,

a multimodal non-pharmaceutical approach to those diagnosed with any

stage of Alzheimer’s disease. Through the use of a thematic structured 12

Step approach, this method incorporates person centered themes from the

group participants. Clinical cases, through video and research datawill illus-

trate how those individuals living with Alzheimer’s disease can directly

identify feeling better, thinking clearer when engaging in body relaxation,

guided mediation and the creative arts process. Methods: Data on falls

and aggressive behaviors on a gero-psychiatric unit at Edward Hospital

were collected through nursing staff one full year prior to study. In 2011,

all staff on the unit engaged in a 2 day- 14 hour training on the TTAP Meth-

od�, training components included howAD progresses, the neuroscience of

how art, music and creative expression stimulates specific brain regions, and

the utilization of themes engages patients diagnosed with AD the ability to

use long term , meaningful memories.Results:Results after a six month pe-

riod demonstrated a significant reduction by over 80 percent on aggressive

behaviors (40 hours per month down to 6 hours per month) and fall de-

creased from 6 falls on average per month to 4 falls. The hospital Chief ad-

ministrator calculated and published a direct healthcare savings in nursing

supervisor staff of over $80,000.00 during the first six months after the

TTAPTraining. In 2013 the hospital received continued educational funding

in which to study additional effects including, depression, withdrawal, med-

ication usage, readmissions and aggressive behaviors over a 12 month pe-

riod from 2013 through 2014. This replicable approach is conducted

through certification training in over 17 facilities nationally proven to en-

hance emotional interactions, stimulates socialization, decrease aggressive

behaviors and falls while increases cognitive functioning and dramatically

reduce healthcare costs. Conclusions: Social change through eduction is

paramount in caring for the ever growing numbers of people who will be di-

agnosed with AD over the next 2 decades. Non -pharmacuetical aproaches

can save our country trillions of dollars in helathcare cost and are currently

being proven highly effective.

P1-369 EFFECT OFAPOE-ε4 CARRIER STATUS ON

DONEPEZIL RESPONSE IN PEOPLE WITH MILD-

TO-MODERATE ALZHEIMER’S DEMENTIA

JeffreyWaring1, Qi Tang2, Weining Robieson1, David King1, Ujjwal Das1,

Jordan Dubow1, Sandeep Dutta1, Gerard Marek1, Laura Gault1, 1AbbVie

Inc., North Chicago, Illinois, United States; 2AbbVie Inc., North Chicago,

Illinois, United States. Contact e-mail: jeff.waring@abbvie.com

Background: Previous studies examining the influence of the apolipopro-

tein E (APOE)-ε4 allele on the clinical response to acetylcholinesterase

treatment in Alzheimer’s dementia patients have yielded inconsistent re-

sults. Data on the donepezil response from 3 studies in subjects with

mild-to-moderate Alzheimer’s dementia were pooled to examine this rela-

tionship. Methods: Data from 3 multinational, randomized clinical studies

with a 12-week treatment duration, similar study design and a statistically

significant response to donepezil were pooled. Patients with mild-to-moder-

ate Alzheimer’s dementia (Mini-Mental Status Examination [MMSE] score

of 10-24, inclusive) provided DNA during study screening. APOE - ε 4 car-

rier status was determined using pyrosequencing. The change from baseline

to final observation on the 13-item ADAS-Cog total score in the intent-to-

treat population was analyzed using ANCOVAwith terms of age, treatment,

study site, APOE -ε4 allele status, using baseline ADAS-Cog score as a co-

variate. Results: Placebo (N¼170) and donepezil (N¼165) patients had

a mean (SD) age of 72 (8.5) years and a mean (SD) baseline MMSE of 19

(3.9). Although the interaction between APOE -ε4 carrier status and treat-

ment was not significant (P ¼0.61), donepezil significantly improved

ADAS-Cog scores versus placebo in both the APOE -ε4 carriers (donepezil

[N¼81], placebo [N¼94], LS mean difference from placebo ¼ -2.34, P

¼0.01) and noncarriers (donepezil [N¼84], placebo [N¼76], LS mean dif-

ference from placebo ¼ -1.71, P ¼0.05). The baseline to final change in

ADAS-Cog scores did not differ significantly (P¼0.89) among donepezil pa-

tients in terms ofAPOE -ε4 allele copynumber: 0APOE -ε4 alleles (LSmean

[SE] change from baseline ¼ -4.09 [0.67], N¼84); 1 allele (-2.97 [0.73],

N¼72); 2 alleles (-2.74 [1.98],N¼9).Of note, themagnitude of the donepezil

treatment response was similar in APOE -ε4 carriers and noncarriers; how-

ever, the carrier group exhibited a smaller placebo response than the noncar-

rier group (LS mean difference baseline to final ¼ -0.60 versus -2.38, P

¼0.05).Conclusions:Therewas no significant effect of APOE -ε4 genotype

on the donepezil response in these mild-to-moderate Alzheimer’s dementia

patients. APOE -ε4 carriers in the placebo group exhibited a smaller change

from baseline on the ADAS-Cog than noncarriers. Thus, APOE -ε4 geno-

type status may be useful for randomization in future clinical trials.

P1-370 THE EFFECTS OF EXERCISE ON MEMORY

PERFORMANCE IN OLDER ADULTS WITH

PROBABLE MILD COGNITIVE IMPAIRMENT: A

6-MONTH RANDOMIZED CONTROLLED TRIAL

Lindsay Nagamatsu1, Alison Chan2, Jennifer C. Davis3, B. Lynn Beattie3,

Peter Graf3, Michelle W. Voss4, Devika Sharma1, Teresa Liu-Ambrose1,1University of British Columbia, Vancouver, British Columbia, Canada;2Centre for Hip Health andMobility, Vancouver, British Columbia, Canada;3UBC, Vancouver, British Columbia, Canada; 4University of Iowa, Iowa

City, Iowa, United States. Contact e-mail: lindsay@psych.ubc.ca

Background: In this study, we report our secondary findings from a random-

ized controlled trial on the effects of resistance training and aerobic training on

memory in older adults with probable mild cognitive impairment (MCI).MCI

is often considered a precursor to dementia; hence, identifying effective treat-

ment strategies could prevent or delay the onset of neurodegenerative disease.

Methods: Our study included 86 women aged 70-80 years, who were