1
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, P ¼ 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) ¼ 2.93, 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 3 4 GENOTYPE Angela Hanson 1 , Laura Baker 2 , Maureen Callaghan 3 , Brenna Cholerton 3 , Jennifer Bayer-Carter 3 , Suzanne Craft 3 , 1 University of Washington Medical Center, Seattle, Washington, United States; 2 University of Washington School of Medicine, Seattle, Washington, United States; 3 Veterans 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 70.4 6 7.7, and 27 with MCI, age 72 6 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 both MCI 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 (6.3 6 9.4 for E4+ versus -1.0 6 10.9 for E4-, P ¼ 0.03). Whereas immediate story recall scores com- pared to control were higher only for the E4 normal group (6.5 6 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 INHIBITOR FOR ACETYLCHOLINESTERASE AND b-SECRETASE DERIVED FROM BENZALKONIUM CHLORIDE AND PEPDIDOMIMETICS Boopathy Rathanam 1 , Lakshmi Venkatachalam 2 , Aarthi Krishnan 2 , 1 Bharathiar University, Coimbatore, Tamil Nadu, India; 2 Bharathiar 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 Joshi 1 , Biradar Siddu 2 , 1 Division of Neuropharmacology, SaradaVilas College of Pharmacy, Mysore, Karnataka, India; 2 SET 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 in memory of young and aged mice. 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. Poster Presentations: P2 P388

Molecular docking of novel hybrid inhibitor for acetylcholinesterase and β-secretase derived from benzalkonium chloride and pepdidomimetics

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Page 1: Molecular docking of novel hybrid inhibitor for acetylcholinesterase and β-secretase derived from benzalkonium chloride and pepdidomimetics

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.