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Tackling Dog’s age related
cognitive decline with cognitive decline with
polyphenols
Anne LEPOUDERE
VIVAE R&D Manager,
DIANA PetFood
• CONTEXT: Increase of Pet’s lifespan
• AGEING: A complex biological process, with consequences on Brainconsequences on Brain
• Market Strategies to tackle age related physiological changes with a focus on polyphenols
• Example of a grape extract and blueberry combination
CONTEXT: Increase of Pets’ Lifespan
Average weight (kg) 4,5 kg < 9 kg 9-23 kg 23-50 kg
Average lifespan (y) 12,1 11,3 10,8 11,1
Main breeds •Domestic shortair •Chihuahua •Beagle •German shepherdMain breeds •Domestic shortair
•Domestic medium hair
•Domestic longhair
•Chihuahua
•Scottish terrier
•Shih tzu
•Yorshire terrier
•Beagle
•Boxer
•Cocker spaniel
•Pit bull
•German shepherd
•Golden retriever
•Labrador retriever
•Rottweiler
Sources:
•Banfield State of Pet Health 2013 report
•Rachel V. Poulin, Coral Springs Animal
Hospital, 2015
+ 10%(2002-2012)
+ 4%(2002-2012)
• Healthy ageing is a challenge for the Senior population
� 45M dogs around 7-years-old in USA & EU Bosch, 2012
� Need for comfort in the top 5 considerations in Caring for Geriatric Patients Rachel V. Poulin, Coral Springs Animal Hospital, 2015
AGEING: A complex biological process
Progressive reduction of the ability to maintain body
homeostasis � Susceptibility to diseases Shearer et al., 2010
PRO-OXIDANTANTIOXIDANT
Accumulation of oxidants by
normal metabolism damages of
protein (PCO), lipids (MDA) and
nucleotids (8-dGOH)
Decrease of endogenous
antioxidant enzymes such as
catalase, glutathione and
superoxide dismutase
PRO-OXIDANT
SPECIES
ANTIOXIDANT
SPECIES
Head, 2009; Sechi 2015
Neurodegeneration and Cognitive impairment
BRAIN AGEING: what happens?
• Early metabolic alterations
– Decreased glucose metabolismDysfunction in insulin IGF-1 receptors
• Morphological changes
– Organ level
– Neuron level
– Synapse
AGEING: Brain morphological changes
� Loss of BRAIN structure
= Cerebral atrophy
�Dogs and Cats’ brain aging close �Dogs and Cats’ brain aging close
to humans’ Fast et al., 2013
�Cognitive Dysfunction Syndrome
(CDS) is a model of Alzheimer
Disease
�Senile plaques, which consist of
extracellular deposits of fibrilized
Beta-amyloid protein
AGEING: Neuron morphological changes
� Alteration of
NEURON structure by
excess of Reactive excess of Reactive
Oxygen Species
� Reduction of the
number of neurons
AGEING: Synapse changes
� Alteration of synaptic plasticity
– Evolution of synapses
– Changes in signalization pathways
� Alteration of cognitive processes,
particularly memory
•Williams et al., 2008
•Li et al., 2009
•Rendeiro et al., 2013
•De Nicolo et al., 2013
Introduction to the Cognitive
Dysfunction Syndrome (CDS)
Market strategies to tackle age related
physiological changes
• Morphological and metabolic changes are irreversible
• Objectives of nutritional & behavioral interventions:
– Decrease the severity of symptoms
– Delay process development
BEHAVIORAL
Environmental enrichmentNUTRITIONAL
-Medium-chain Triacylglicerides
(MCT)
-Omega-3 (DHA)
-Vitamins of the B group
-Antioxidants
POLYPHENOLS
Polymers Glycosides Aglycones
Metabolic fate of polyphenols
Exc
reti
onBilary secretion
Deconjugation
MICROFLORA
metabolization
Fecal excretion
Source: adapted from Liu & Hu (2007), Duynhoven 2010
Intestinal mucosa
Uri
na
ryE
xcre
tio
n
Depolymerization Deconjugation
Polyphenol interest for tackling age related
cognitive decline
• Demonstrated Antioxidant, Anti-inflammatory bioactivities
• Beneficial effects on spatial memory & long-term memory Van Praag et al., 2007; Rendeiro et al., 2012; Harada et al., 2012
• In vitro & in vivo studies have shown their bioavailability in the brain Prasain et al., 2009; Milbury and Kalt, 2010; Juan et al., 2010
• Systemic effects depend on polyphenols interactions Hahnineva
2010, Dudonné 2016
Combination of Grape extract & blueberry polyphenols to
prevent age related cognitive decline in dogs: PHENOMIND
1. Safety
INITIAL REQUIREMENTS
1. Spatial learning
COGNITION
Antioxidant properties
METABOLIC EFFICIENCY
13
2. Palatability
3. Product specification
4. Kinetics of absorption
2. Memory
Antioxidant properties
A. Adult dog
B. Aged dogs (poster)
Combination of Grape extract & blueberry polyphenols to
prevent age related cognitive decline in dogs: PHENOMIND
1. Safety [Martineau, 2015]
6 months, 24 dogs
Diet : control, dose x1, x5, x10
���� Phenomind safe in dogs up to 10 times the recommended
dosage
1. Safety
� Safety Checked
2. Palatability
INITIAL REQUIREMENTS
2. Palatability
14
2. Palatability
� No palatability impact
3. Product specification� Polyphenols characterization
4. Kinetics of absorption
�Well absorption
�No extrusion impact
6 versus tests in cats and dogs: inclusion OR coating application
�No palatability impact
4. Kinetics of absorption
6 dogs, 7 days, cross over design
Phenomind application: Capsule or Inclusion in Pet Food
� Increase of specific polyphenol metabolites in dogs plasma
� Equivalence of capsule administration and Pet Food inclusion
application
Scientific support Phenomind
4. Kinetics of absorption
6 dogs, 7 days
Same Phenomind supplementation = in Capsule or in Inclusion
in the diet
1. Safety � Safety Checked
2. Palatability � No palatability impact
INITIAL REQUIREMENTS
15
� Phenomind increases specific polyphenol metabolites in
dogs plasma
� Same conclusion with 2 administration way = Phenomind
pass through the extrusion process.
3. Product specification
� Polyphenols
characterization
4. Kinetics of absorption
�Well absorption
�No extrusion impact
Combination of Grape extract & blueberry polyphenols to
prevent age related cognitive decline in dogs: PHENOMIND
� Phenomind increases total antioxidant status and induces
1. Antioxidant properties
A. Adult dog
9 dogs, 28 days
METABOLIC EFFICIENCY
16
� Phenomind increases total antioxidant status and induces
several gene expression associated with decrease oxidative
stress in dogs
9 dogs, 28 days
B. Aged dogs
�Impact gene expression
with antioxidant property
Combination of Grape extract & blueberry polyphenols to
prevent age related cognitive decline in dogs: PHENOMIND
1. Spatial learning [Bensalem, 2016]
20 adult and 24 aged mice
8 weeks
COGNITION
�Phenomind supplementation helps to develop more
17
8 weeks
Morris water maze�Phenomind supplementation helps to develop more
spatial strategies in mice.
Scientific support Phenomind
2. Memory[Fragua & Lepoudère 2017]
35 Aged dogs
56 days
COGNITION
18
56 days
Phenomind vs control
Scientific support Phenomind
2. Memory[Fragua & Lepoudère 2017]
35 Aged dogs
56 days
COGNITION
19
56 days
Phenomind vs control
� Dogs fed Phenomind-rich diets have a positive effect on
working memory.
Take Home messages
• Brain ageing is characterized by drastic changes in its structure and functionality with consequences on cognitive processes, especially memory
• Nutritional strategies focusing on the prevention of oxidative • Nutritional strategies focusing on the prevention of oxidative stress may prevent age-related cognitive alterations and should be started as soon as possible
• A polyphenol combination of blueberry and grape extract improved working memory in old dogsPossibly thanks to an improvement of synapse plasticity &
neurogenesis
