Effect of APOE-ε4 carrier status on donepezil response in people with mild-to-moderate Alzheimer's...
Transcript of Effect of APOE-ε4 carrier status on donepezil response in people with mild-to-moderate Alzheimer's...
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: [email protected]
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: [email protected]
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: [email protected]
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