Poster Presentations: P2P388
type Ab deposits, and oxidative damage in the brain. Methods: Nine aged
beagles (98-115 months) were treated with a medical food cocktail con-
taining (1) an extract of turmeric containing 95% curcuminoids; (2) an
extract of green tea containing 50% epigallocatechin gallate; (3) N-ace-
tyl cysteine; (4) R-alpha lipoic acid; (5) an extract of black pepper con-
taining 95% piperine. Nine similarly aged dogs served as placebo-treated
controls. We used a modified Wisconsin General Test apparatus for be-
havioral testing of the dogs for 10 or 12 trials/day, 5 days/week, with
food rewards. Data acquisition was controlled using dedicated software
(DOGMA). After a 1 month wash in, dogs were given a landmark dis-
crimination task to measure spatial attention. Results: For the first 2
months of treatment, we observed a gradual but nonsignificant improve-
ment in attention in treated animals as they progressively solved the prob-
lem using increasing landmark distances (0, 5, 18, 14 cm from the center of
the correct object to be displaced). After 3 months of treatment, 13 dogs
completed a 20-day variable distance version of the task. As compared
to placebo-treated animals, dogs receiving the medical food cocktail had
significantly lower error scores (t(11)¼ 4.3, P¼ 0.001) and were more ac-
curate across all distances (F(1,9) ¼ 20.7, P ¼ 0.001). Blood biochemical
measures from treated dogs had reduced aspartate transaminase (AST)
(t(15) ¼ 3.5, P ¼ 0.003) and creatinine phosphokinase (CPK) (t(15) ¼2.93, P ¼ 0.01), indicating no liver or muscle toxicity with consumption
of the medical food cocktail. Brain Ab remained unchanged in treated
dogs and there appeared to be no change in gliosis. Conclusions: Our re-
sults indicate that this medical food cocktail may be beneficial for reducing
or preventing symptoms associated with aging and AD.
P2-363 INFLUENCE OF DIET MACRONUTRIENTS ON
COGNITION AND THE INTERACTION WITH
APOE 34 GENOTYPE
Angela Hanson1, Laura Baker2, Maureen Callaghan3, Brenna Cholerton3,
Jennifer Bayer-Carter3, Suzanne Craft3, 1University of Washington Medical
Center, Seattle, Washington, United States; 2University of Washington
School of Medicine, Seattle, Washington, United States; 3Veterans Affairs
Puget Sound Health Care System, Seattle, Washington, United States.
Background: Diets high in saturated fat and simple sugar may be involved
in the pathogenesis of Alzheimer’s disease, but the mechanisms are un-
known. We designed a diet intervention to study the interactions of macro-
nutrients, metabolism markers, and cognition. Methods: Participants
included adults with normal cognition or mild cognitive impairment
(MCI). The “control” diet consisted of 25% total calories from fat (7% sat-
urated fat), and glycemic index< 55. The “high” diet consisted of 50% total
fat (25% saturated fat), and a glycemic index of > 70. Outcome measures
included insulin, glucose, lipids, and cognitive tests (category fluency, im-
mediate and delayed story recall, and trails B). Each participant ingested
both diets on different days in random order. Results were analyzed using
repeated measures ANOVA and Pearson correlations. Results:We enrolled
19 participants with normal cognition, age 70.46 7.7, and 27 withMCI, age
726 6.9. Normal E4- subjects scored the lowest on cognitive tests after in-
gesting the high diet, whereas E4+ subjects scored better after the high diet,
for bothMCI and normal conditions depending on the test. For example, cat-
egory fluency score was higher for all E4+ subjects after the high diet com-
pared to the control diet, irrespective of diagnosis (6.36 9.4 for E4+ versus
-1.06 10.9 for E4-, P¼ 0.03). Whereas immediate story recall scores com-
pared to control were higher only for the E4 normal group (6.56 2.9 com-
pared to -1.8 6 1.7 for normal E4-, 0.3 6 1.9 for MCI E4+, p value .04).
Post-prandial lipid measures correlated with cognitive scores according to
E4 status. For example, meal-induced LDL levels correlated positively
with a higher trails B time for the MCI E4+ group on the high diet (P ¼.005), but not for the MCI E4- group. Conclusions: Preliminary data sug-
gest that a diet low in saturated fat and glycemic index benefits subjects
with normal cognition, particularly those without an E4 allele. These data
also suggest that unlike chronic diet studies, an acute diet study with
a meal high in saturated fat seemed to improve cognition for adults with
an E4 allele.
P2-364 MOLECULAR DOCKING OF NOVEL HYBRID
INHIBITORFORACETYLCHOLINESTERASEAND
b-SECRETASE DERIVED FROM BENZALKONIUM
CHLORIDE AND PEPDIDOMIMETICS
Boopathy Rathanam1, Lakshmi Venkatachalam2, Aarthi Krishnan2,1Bharathiar University, Coimbatore, Tamil Nadu, India; 2Bharathiar
University, Coimbatore, Tamil Nadu, India.
Background: Hybrid inhibitors that bind both to Acetylcholinesterase
(AChE) and b- Secretase (BACE) has a remarkable influence on Alzheim-
er’s drug research. Benzalkonium chloride (BAC), a detergent, is unique in
inhibiting esterase without affecting yet another genuine aryl acyl amidase
(AAA) activity of human AChE. Through inhibitory studies, we deduced
that alkyl group of BAC is interacting at peripheral anionic site (PAS) of
AChE. PAS is better known for its role in amyloid beta peptide aggregation.
Methods: Intrigued by this distinct effect of BAC on AChE and similarly
effect of pepdidomimetics on BACE, we designed 22 hybrid ligands con-
taining the alkyl group of BAC and pepdidomimetic inhibitors of BACE.
Possible interactions between such hybrids with either AChE or BACE
were investigated in docking experiments using AutoDock 4.0 and Schro-
dinger Maestro 9.0.Results:Among the 22 novel heterodimers as inhibitor,
CID-929 showed potent binding ability with AChE and BACE on compara-
ble basis better than the known specific inhibitors of AChE and BACE.Con-
clusions: The compound identified will serve as a novel ligand/drug against
the causative proteins of Alzheimer’s disease.
P2-365 COMMUNICATION STRATEGIES FOR
CAREGIVERS AND PATIENTS WITH MILD-TO-
MODERATE DEMENTIA
Daryl Lorell, MMSC Rehabilitation Center, Marshalltown, Iowa, United
States.
Background: Caregivers may be at a loss in communicating with their
loved one with Alzheimer’s disease. This may lead to frustration for both
parties and anxiety for the patient. Due to communication barriers, the pa-
tient may exhibit behaviors such as, asking for repetition, making denigrat-
ing comments about his/her memory or self-worth and/or become verbally
reclusive. Consequently, it is of benefit to teach communication strategies to
the patient with Alzheimer’s disease, if able, and their caregivers. In 1995,
Danielle Ripitch, Ph.D. developed the FOCUSED Communication Strate-
gies for caregivers. FOCUSED stands for Face-to-Face, Orient to topic,
Continue topic, Unstick word blocks, Structure questions, Exchange con-
versation and Direct statements. In addition to FOCUSED, communication
strategies developed over years of working with patients and their caregivers
will be presented.
P2-366 PSYCHOPHARMACOLOGICAL INVESTIGATIONS
ON THE BENEFITS OFAGERATUM CONYZOIDES
IN THE MODULATION OF
NEURODEGENERATIVE DISORDERS
Hanumanthachar Joshi1, Biradar Siddu2, 1Division of
Neuropharmacology, Sarada Vilas College of Pharmacy, Mysore,
Karnataka, India; 2SET College of Pharmacy, Dharwad, India.
Background: Alzheimer’s disease (AD) is a neurodegenerative disease of
central nervous system leads to dementia, behavioral and cognitive impair-
ments. The present study was designed to investigate the effect of Ageratum
conyzoides (AC) on learning and memory in mice. Methods: (EPM) and
Morris Water Maze (MWM) were the exteroceptive behavioral models
and like Scopolamine, Natural Ageing inducing amnesia were interoceptive
behavioral models. The whole brain AChE activity was also determined.
Results:AC (250, 500, and 750 mg/kg, p.o.) produced a dose dependent im-
provement inmemory of young and agedmice. Furthermore, it also reversed
the amnesia induced by scopolamine (0.4 mg/kg, i.p) and natural ageing. It
also produced a profound reduction in the whole brain Acetylcholinestrease
activity. Conclusions: Hence AC may prove to be a useful remedy for the
treatment of preliminary symptoms of AD.