A randomized controlled trial investigating the effect of Pycnogenol and Bacopa CDRI08 herbal medicines on cognitive, cardiovascular, and biochemical functioning in cognitively healthy elderly people: the Australian Research Council Longevity Intervention (ARCLI) study protocol (ANZCTR12611000487910)
A randomized controlled trial investigating the effect of Pycnogenol and Bacopa CDRI08 herbal medicines on cognitive, cardiovascular, and biochemical functioning in cognitively healthy elderly people: the Australian Research Council Longevity Intervention (ARCLI) study protocol (ANZCTR12611000487910)
Con K Stough 0
Matthew P Pase 0
Vanessa Cropley 2
Stephen Myers 1
Karen Nolidin 0
Rebecca King 0
David Camfield 0
Keith Wesnes 0 5
Andrew Pipingas 0
Kevin Croft 4
Dennis Chang 3
Andrew B Scholey 0
0 Centre for Human Psychopharmacology, Swinburne University of Technology , Melbourne , Australia
1 Southern Cross University , Lismore , Australia
2 Melbourne Neuropsychiatry Centre, The University of Melbourne , Australia
3 Complemed, NICM, University of Western Sydney , Australia
4 School of Medicine and Pharmacology, University of Western Australia , Australia
5 CDR , Bracket, Goring-On-Thames, England
Background: One of the major challenges associated with our ageing population is the increasing incidence of age-associated cognitive decline, which has significant implications for an individual's ability to lead a productive and fulfilling life. In pure economic terms the costs of ageing reflects decreased productivity and engagement with the workforce. The maintenance of brain health underpinning intact cognition is a key factor to maintaining a positive, engaged, and productive lifestyle. In light of this, the role of diet, including supplementation with nutritional and even pharmacological interventions capable of ameliorating the neurocognitive changes that occur with age constitute vital areas of research. Methods: In order to reduce cognitive ageing, the ARC longevity intervention (ARCLI) was developed to examine the effects of two promising natural pharmacologically active supplements on cognitive performance. ARCLI is a randomized, placebo-controlled, double-blind, 3-arm clinical trial in which 465 participants will be randomized to receive an extract of Bacopa monnieri (CDRI08 300 mg/day), Pycnogenol (150 mg/day), or placebo daily for 12 months. Participants will be tested at baseline and then at 3, 6 and 12 months post-randomization on a wide battery of cognitive, neuropsychological and mood measures, cardiovascular (brachial and aortic systolic and diastolic blood pressures as well as arterial stiffness), biochemical (assays to measure inflammation, oxidative stress and safety) as well as genetic assessments (telomere length and several Single Nucleotide Polymorphisms). The primary aim is to investigate the effects of these supplements on cognitive performance. The secondary aims are to explore the time-course of cognitive enhancement as well as potential cardiovascular and biochemical mechanisms underpinning cognitive enhancement over the 12 months of administration. ARCLI will represent one of the largest and most comprehensive experimental clinical trials in which supplements are administered to elderly participants. Results from ARCLI may help develop novel preventative health practices and nutritional/pharmacological targets in the elderly for cognitive and brain health.
Trial registration: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12611000487910
Background and Rationale
With increasing life expectancies and the maturation of
the baby boom generation, adapting to the challenges
posed by the ageing population has been identified as
one of the major issues facing contemporary society .
Human ageing has significant societal, economic, health
and, importantly, personal costs. In pure economic
terms the costs of ageing reflects decreased productivity
as well as increased levels of reliance on public services
for health and social support but this also has obvious
ramifications for older peoples ability to lead fulfilling
lives. Increasing age is associated with a cluster of
illnesses many involving oxidative stress and low level
chronic inflammation. These include cardiovascular and
respiratory disease and, importantly neurological
conditions such as Parkinsons disease (PD) and Alzheimers
What is Cognitive Ageing?
Individual age-related changes in cognition vary greatly.
However research in cognitive aspects of ageing
(typically in 60 to 90 year-olds) has identified consistent
deficits in: reasoning and decision making; spatial abilities;
perceptual-motor and cognitive speed; and most
robustly memory (e.g. ). Longitudinal studies of aged
populations illuminate the time-course of cognitive
deterioration. Using 5 to 10 year re-test intervals significant
decrements across most cognitive capacities become
evident. A recent review of longitudinal ageing studies
concludes that crystallized intelligence (e.g., factual
knowledge) remains intact until late ageing whereas
measures of speed, information processing and aspects
of memory (e.g., working memory) are more sensitive to
decline from age 60 .
Brain Ageing and Oxidative Stress
Neuroimaging studies reveal that increasing age is
reliably associated with ventricular enlargement, reduction
in gross brain volume, reductions in frontal and
temporo-parietal brain volume, higher levels of cortical
atrophy, and increased white matter hyperintensities .
Ultimately, shrinkage of cortical volume reduces
cognitive capacity  and age-related increases in
neuropathological events such as beta-amyloid protein
deposition and formation of neurofibrillary tangles
represent significant risk factors for cognitive decline
and AD. Neuropathological events such as beta-amyloid
deposition are not exclusive to neurodegenerative
disorders such as AD, in fact occurring in a large proportion
of cognitively intact individuals. For example, in one
study the proportion of non-clinical subjects with
betaamyloid deposits ranged from 3% in a 36-40 age group
to 75% in a 85+ age group .
Alongside age-associated cortical degeneration ,
there exist numerous microscopic insults related to
oxidative stress and free radical damage. Free radicals are
molecules with unpaired electrons. These molecules are
highly unstable and can cause damage to proteins, lipids,
carbohydrates and nucleotides . Free radicals formed
in the brain produce significant cellular damage, and
mediate processes which result in neural cell death on
large scales . Between 95% and 98% of free radicals
and Reactive Oxygen Species (ROS) (O2 -, HO , H2O2)
are formed by mitochondria as by-products of cellular
respiration. Studies of mitochondria isolated from the
brain show that 2-5% of total oxygen consumed yields
ROS , these highly reactive molecules make a
significant contribution to the peroxidation of principal cell
structures (e.g. membrane lipids) . Brain tissue is
particularly susceptible due to its disproportionately high
metabolic rate and levels of oxygen, the cytotoxic actions
of glutamate, and its high concentrations of
peroxidisable unsaturated fatty acids . Ageing decreases the
brains ability to combat the actions of free radicals and
is associated with increased levels of pro-oxidant
mediators and decreased antioxidant levels . The
relationship between cognition and oxidative stress is evident in
the extensive damage caused by free radicals in
agerelated neurological conditions [10,11], and animal
models of age-related oxidative injury with central cognitive
and behavioural impairments . Concurrent with the
normal age-related cognitive changes are increases in the
formation of brain ROS resulting in significant damage
to DNA, proteins and in particular membrane lipids .
Although multiple factors precipitate oxidative stress
throughout the body, the brain is particularly vulnerable
and its cumulative effects may account for the delayed
onset and progressive nature of Alzheimers and
Parkinsons dementias, as well as normal age-related mental
Antioxidants and Cognition
The central role of oxidative stress in age-related
cognitive decline and neurodegenerative diseases has driven
numerous studies examining the potential benefits of
antioxidants in altering, reversing, or forestalling
neuronal and behavioural changes (e.g. ). Anti-oxidant
supplementation results in improved cognition and
behaviour in aged animals and concurrent decreases in
oxidative insult to neural structures . Human
research in this area is largely limited to epidemiological
studies. These have identified positive associations in
aged individuals between biological levels of dietary
antioxidants (vitamins E and C) and working memory
measures including the Wechsler Memory test . Less
reliable than biological measures, large scale studies
(3000+ participants) have also identified positive
relationships between dietary intake of vitamin C and E and
standardized memory measures . While these
nonclinical trials do not demonstrate causality, the
consensus that memory is the main cognitive variable affected
by antioxidant status is consistent with patterns of
agerelated cognitive decline and the in vivo neuroanatomy
of lipid peroxidation .
Given the consequences of a burgeoning ageing
population, the role of supplementation with nutritional and
pharmacological interventions capable of ameliorating
the neurocognitive changes that occur with age
constitute vital areas of research.
Treatments to Reduce or Ameliorate Brain Ageing
(i) Pycnogenol Neural cells have three systems of
protection and repair in response to oxidative stress; 1)
Enzymatic antioxidants (superoxide dismutase, catalase,
peroxidases); 2) Radical scavenging lipid-soluble
(tocopherols, flavonoids, carotenoids) and water- soluble
(ascorbate, glutathione) antioxidants; and 3) repair
proteases and phospholipases . Pycnogenol is a patented
concentrate consisting of condensed flavonoids isolated
from Maritime Pine bark. Extensive reviews by Packer
et al  and Rohdewald  have established the
antioxidant activity of Pycnogenol in simplified assay
systems, cultured cell models, and perfused organs. There is
evidence that Pycnogenol prolongs the lifetime of the
ascorbate antioxidant and stimulates the synthesis of
antioxidant enzymes inside arterial cells . The
established neuroprotective properties of flavonoids strongly
advocate their use in intervention strategies . Of
these, Pycnogenol is particularly promising, having been
studied extensively in the context of protecting against
oxidative damage to specific neural systems. Kobayashi
 reported that Pycnogenol had neuroprotective
properties in HT-4 neuronal cells subjected to
glutamateinduced cytotoxicity (one of the principle sources of ROS
in the brain . Similarly Liu  and Peng  found
Pycnogenol to inhibit beta-amyloid apoptosis of neurons
and vascular cells, both of which are oxidative processes
that accumulate with age, and are pathological features of
AD. In vivo supplementation to aged animals  results
in biological and behavioural changes consistent with the
slowing of age-related decline in physiology, learning and
memory. Additionally 6 wk Pycnogenol supplementation
to humans resulted in significantly reduced serum low
density lipoprotein and increased plasma oxygen radical
absorbance capacity (ORAC)  - a convenient
although non-specific measure of in vivo antioxidant
(ii) Bacopa Monniera (L.) Wettst. (syn. Bacopa
monniera Hayata & Matsum) has been used in traditional
Ayurvedic medicine for various indications including
memory decline, inflammation, pain, pyrexia, epilepsy and
as a sedative . Bacopa contains Bacoside A and
Bacoside B which are steroidal saponins believed to be essential
for the clinical efficacy of the product. While Bacopa has
been reported to have many actions, its memory
enhancing effects have attracted most attention and are
supported by the psychopharmacology literature. Behavioural
studies in animals have shown that Bacopa improves
motor learning, acquisition and retention, and delay
extinction of newly acquired behaviour . Although the
exact mechanisms of action remain uncertain, evidence
suggests that Bacopa may modulate the cholinergic system
and/or have antioxidant and metal chelating effects
[31,32]. Bacopa may also have anti inflammatory ,
anxiolytic and antidepressant actions [34,35], relaxant
properties in blood vessels  and adaptogenic activity
. Chronic administration of Bacopa inhibits lipid
peroxidation in the prefrontal cortex, striatum and
hippocampus via a similar mechanism to vitamin E . In an
animal model of AD, there was a dose-related reversal by
Bacopa of cognitive deficits produced by the neurotoxins
colchicine and ibotenic acid . In rodents, Bacopa
inhibited the damage induced by high concentrations of
nitric oxide in astrocytes . Memory deficits following
cholinergic blockade by scopolamine were reversed by
Bacopa treatment. In animal studies Bacopa reduced lipid
peroxidation induced by FeSO4 and cumene
hydroperoxide indicating that, similarly to the chelating properties of
EDTA, it acts at the initiation level by chelating Fe++ .
More recently in transgenic mice, Bacopa
supplementation reduced specific amyloid peptides by up to 60% whilst
also improving memory performance . Thus, Bacopa
appears to have multiple modes of action in the brain all
of which may be useful in ameliorating cognitive decline
in the elderly. These include: (i) direct pro-cholinergic
action; (ii) anti-oxidant (flavonoid) activity; (iii) metal
chelation; (iv) anti-inflammatory effects; (v) improved blood
circulation; (vi) adaptogenic activity; and (vii) removal of
b-amyloid deposits. In contrast to anti-oxidants such as
Vitamin C and E, and specific anti-oxidants such as
Pycnogenol, the polypharmacological actions of Bacopa
potentially act on several pathological changes in elderly
brains in concert. This potential is supported by a limited
number of clinical trials into the neurocognitive effects of
Pycnogenol and, to a greater extent, Bacopa. Both
substances are capable of improving memory functioning in
cognitively intact cohorts, with Pycnogenol improving
working memory  and Bacopa preferentially
enhancing secondary memory (reviewed in Pase et al.). In
both cases effects are evident at three months of daily
administration, but not earlier.
Aims and study hypotheses
Extending upon preliminary findings [42,44,45], the
primary aim of the current study is to examine the
individual chronic 12 month effects of Bacopa (300 mg daily),
and Pycnogenol (150 mg daily) on cognitive performance
in a healthy elderly population. The secondary aims of
the current study are two fold. Firstly, to investigate the
time course of cognitive ehancement with follow-up
testing at 3, 6 and 12 months. Secondly, to examine putative
mechanisms underpinning any cognitive enhancing
actions of the supplements by examining relationships
between cognitive, biological (biochemical and genetic)
and cardiovascular variables over the 12 months. By
examining the interrelationship between inflammation,
oxidative stress, cardiovascular health and cognitive
perfromance, the current study aims to identify modifiable
risk factors for cognitive decline that can be targeted by
supplementation. It is hypothesized that all supplements
will improve measures of cognitive performance, relative
to placebo, at all time points with the greatest cognitive
effects observed at 12 months.
ARCLI will be conducted at the Centre for Human
Psychopharmacology, Swinburne University, Melbourne,
Australia. In the first year approximately 1/3 of the
cohort will be enrolled. In years 2 and 3 additional
recruitment will occur at the University of Western
Sydney (Sydney, Australia).
A total of 465 healthy, elderly participants aged between
60 and 75 years will take part in the study. This
restricted age range was chosen due to the large
variation in cognitive abilities and trajectories associated with
ageing. Participants will be randomized to receive one of
three daily treatments for 12 months: (a) 300 mg
Bacopa (KeenMind CDRI 08 extract); (b) 150 mg
Pycnogenol; or (c) placebo. Participants will be excluded
from participation if they are a current smoker; have a
psychiatric or neurological disease; significant endocrine,
gastrointestinal or cardiovascular disorder; other
disorder affecting food metabolism; recent history (past 5
years) of chronic/severe illness (longer than 6 weeks);
current regular alcohol use exceeding 14 standard drinks
per week for women and 28 standard drinks per week
for men; vision that is not corrected to normal. To be
eligible, participants cannot be taking psychoactive
medication including, antidepressants, antipsychotics,
anxiolytics, cholinesterase inhibitors, illicit drugs or significant
cognitive enhancing drugs (e.g. chronic intake of
substances such as Ginkgo). Participants who are irregular
users of vitamin or herbal supplements will be asked to
stop taking them for the duration of the trial.
Participants who are regular users (defined as daily intake for
greater than 3 months) of vitamins or herbal
supplements will be asked to maintain the same habits
throughout the trial. Participants with either global
cognitive impairment or significant levels of depressive
symptoms, as determined by a score < 24 on the Mini Mental
State Examination (MMSE) or a score > 19 on the
Geriatric Depression Scale respectively, will be excluded. To
ensure that participants do not have probable dementia,
those scoring between 24-26 on the MMSE will be
administered the Dementia Rating Scale II (DRS-II). Any
questionable cases on the DRS-II will be discussed by the
ARCLI participant safety committee for agreement on
eligibility. The study was ethically approved by the
Swinburne University Human Research Ethics Committee
(project number 2010/106) and all participants will
provide written informed consent. The trial has been
registered with the Australian and New Zealand Clinical Trials
Eligible participants are required to attend five testing
session. An overview of the testing sessions is provided in the
clinical trial flow chart (Figure 1). During the first session,
participants are screened for eligibility and a detailed
history is taken. Eligible participants are then asked to give
blood and to complete the cognitive test batteries multiple
times. This allows the participant to familiarize themselves
with the cognitive tasks and minimises practice effects (as
well as establishing that the participant lies within
established norms for their age group). Cognitive data obtained
during the training visit will not be included in statistical
analysis. Visit 2 involves baseline assessment of all
measures and randomization to treatment. Participants are to
commence taking their assigned treatment on the day
following their baseline assessment. As depicted in Figure 1,
visits 3 to 5 involve follow-up assessment at 3, 6 and 12
months post randomization. At the 12 month assessment,
participants will be asked to return any remaining
supplements, such that they can be counted enabling the
investigators to estimate compliance to treatment.
Figure 1 ARCLI protocol flow diagram.
The sample size for this study is 465 participants with 155
participants in each arm. Previous studies using Bacopa
and Pycnogenol have reported statistical significance on
measures of cognition with approximately 100 participants
in each of these studies respectively [42,44]. Based on
these previous studies, the current sample size of 465
ensures adequate power to detect a significant effect 80%
of the time when conducting two-tailed tests using 95%
confidence even when allowing for a 10-20% attrition rate.
(a) The Bacopa supplement used in ARCLI is an extract
of Bacopa monnieri called CDRI08 and is commercially
available as KeenMind (Flordis). This product is
manufactured from the stems, leaves and roots of Bacopa
and is extracted with 50% ethanol. It is standardized to
contain active bacosides at levels of 55% 5%. This
extract has previously been shown to enhance cognitive
performance at this dosage after 3 months of
(b) Pycnogenol (Horphag Research, Geneva,
Switzerland) is a patent extract made exclusively from the bark
of French maritime pine trees (Pinus pinaster).
Pycnogenol contains consistent proportions of bioflavonoids
and is standardized to contain 70 5% procyanidins.
This dosage of Pycnogenol has previously been shown
to enhance memory performance after 3 months of
Randomization and safety
An independent researcher (Medical practitioner) located
at an independent university will be responsible for the
randomization of the study treatments and will chair the
safety committee. Participants will be randomly assigned
to one of the three treatment groups according to a Latin
square design. Randomization codes will be kept in a
sealed opaque envelope in a secure safe and will only be
opened in case of emergency.
The primary study outcome is the effect of
supplementation on cognitive performance as measured by a battery of
well validated and highly sensitive cognitive tests. These
tests will be implemented at baseline and all follow-up
time points (3, 6 and 12 months post baseline). This
battery will include all tasks from the Cognitive Drug
Research (CDR) Computerized Assessment System and
selected tasks from the Swinburne University
Computerized Cognitive Assessment Battery (SUCCAB). Table 1
lists the cognitive measures assessed by the CDR and
SUCCAB batteries. Wechsler intelligence (Wechsler
Abbreviated Scale of Inteligence-WASI) will also be
administered as both an estimate of pre-morbid intelligence as
well as a factor to determine whether IQ predicts response
to any of the supplements.
The CDR battery has been used in well over 1000
clinical trials world wide, is well validated, and has been
shown to be sensitive to the effects of several natural
supplements including Bacopa and Pycnogenol [42,44]. The
SUCCAB is sensitive to the effects of age-associated
cognitive decline and has been recommended for use when
assesing cognitive changes following nutraceutical
supplementation . The SUCCAB has also been shown
sensitive to the effects of a pine bark extract similar to
Pycnogenol . Both the CDR and SUCCAB provide
detailed assessments of memory performance (both short
and long term), a domain of cognition expected to be
modulated by treatment. The cognitive demand battery
 will be implemented to assess the effects of
supplementation on cognitive effort and fatigue whilst the
MMSE  will be used as a dementia screening tool at
intake and to monitor the effects of treatment on global
cognitive decline (after randomization). The Inspection
Time task  and Hick Reaction Time paradigm 
Table 1 Cognitive domains measured by CDR and SUCCAB tests
2 Choice Decision Time
2 Choice Movement Time
4 Choice Decision Time
4 Choice Movement Time
8 Choice Decision Time
8 Choice Movement Time Page 6 of 9 Inspection Time Perceptual Speed
will be used as they provide highly valid and sensitive
assessment of mental speed which has been shown to
slow with increasing age.
A wide range of psychological, cardiovascular,
biochemical and genetic measures will also be collected at
different time points as part of ARCLI. These are described
below and listed in Table 2.
Mood, health and dietary habits
Numerous self-report questionnaires will be used to
assess mood and general health. Depressive symptoms
and state-trait anxiety will be measured with the Beck
Depression Inventory II (BDI-II)  and the
Spielberger State-Trait Anxiety Inventory  respectively.
Further assessment of mood will be performed with the
Profile of Mood Scales  and the Bond and Lader
Visual Analogue Scales . Throughout the trial,
general health, fatigue and sleep quality will be assessed
with the General Health Questionnaire , Chalder
Fatigue Scale  and the Leeds Sleep Evaluation
Questionnaire  respectively. Dietary habits will be inferred
from an in-house Food Frequency Questionnaire.
Brachial pressures, aortic pressures and carotid-femoral
Pulse Wave Velocity (PWV) are not only associated with
cardiovascular disease risk and mortality [59,60] but also
cognitive performance and decline [61,62]. These
variables can all be modified by diet and lifestyle changes
[63-65] and will therefore be monitored throughout the
trial as one possible mechanism by which the study
supplements improve brain function. Brachial blood pressure
Table 2 Summary of the secondary outcomes implemented in ARCLI across all time points
* = Analysis performed for morning participants only
GDS = Geriatric Depression Scale, MMSE = Mini Mental State Examination, DRS = Mattis Dementia Rating Scale, Q = Questionnaire, APOE = Apolipoprotein E, SNP
= Single Nucleotide Polymorphisms, WASI = Wechsler Abbreviated Scale of Intelligence FFQ = Food Frequency Questionnaire, NEO PI-R = NEO Personality-Inventory
Revised, POMS = Profile of Mood States, BMI = Body Mass Index, CRP = C Reactive Protein, MBA = Multiple Blood Analysis, BP = Blood Pressure, PWV = Pulse
will be measured after a 5 minute rest period using a
clinically validated automated sphygmomanometer.
Applanation tonometry of the radial artery will be used
to estimate aortic pressures and wave reflections using a
non-invasive SphygmoCor device. The same
SphygmoCor device will be used to measure PWV through
applanation of the carotid and femoral arteries. In addition to
this assessment, cerebral and common carotid blood flow
velocity and endothelial dependent vasodilation of the
brachial artery may be measured on a subset of
participants using transcranial Doppler and flow mediated
Pre-randomization, one off biochemical assessment will
be conducted to measure glycated haemoglobin
(HbA1c) and insulin levels. Measurement of blood
glucose and insulin will provide a measure of baseline
glucoregulatory efficiency and control, which may
contribute to age-related cognitive decline . At both
baseline and selected follow-up time points, biochemical
markers of oxidative stress, inflammation and safety
profiling will be measured through high sensitivity
C-Reactive Protein, F2-Isoprostanes, inflammatory cytokines
(e.g. TNF-a, IL-2, IL-4, IL-6, IL-10 & IFN-gamma) and
Liver Function Tests.
Blood collected pre-randomization will also be used to
assess a platform of Single Nucleotide Polymorphisms
thought to be related to cognitive/brain function,
general health or response to treatment. This will include
assessment of the APOE4 allele, which is associated
with an increased risk of AD  and cognitive decline
in normal elderly  but also more than 100 targeted
polymorphisms including BDNF, cytokines amongst
others. Genotyping will allow investigation of whether
certain polymorphisms affect response to treatment or
show differential relationships with the cognitive and
biological variables. Telomere length (a marker of
genetic damage) will also be assessed at baseline and 12
months to investigate whether any of the treatments
modulate telomere shortening over the duration of the
The primary analysis will investigate the effects of
treatment on all cognitive outcomes over the course of the
study using Analysis of Variance (ANOVA) techniques.
Other more powerful statistical techniques such as
linear mixed modelling and intention to treat analysis will
be considered. Similar statistical techniques will be used
to investigate the effects of treatment on the secondary
outcomes. Pearsons correlation coefficients will be used
to investigate whether any improvements in cognition
are related to improvements in other variables of
interest such as biochemical, cardiovascular or mood/health
factors. Correlations and regression models may be used
to examine baseline associations between variables.
Results will be considered statistically significant at p <
0.05 corrected for multiple cognitive factors (primary
outcome variables) or p < .05 for secondary outcome
Covariates such as age, gender and baseline cognitive
screening measures (e.g., MMSE and Wechsler
intelligence) will be adjusted for in the analyses. Results will
be presented as appropriate effect sizes with a measure
of precision (95% confidence intervals). Compliance to
treatment will be analysed by counting each participants
remaining supplements once they have completed the
Safety and Data Monitoring Committee
A data and safety committee will comprise the study GP
(Prof Myers), the study nurse, the Chief Investigator
(Prof Stough) and a medical officer attached to the
Centre for Human Psychopharmacology but not otherwise
part of ARCLI.
Given our currently ageing population, research
addressing the issue of cognitive decline in aged individuals is
critical. This issue is further reinforced by the fact that
such cognitive decline frequently precedes various forms
of dementia. The proposed study will be the largest and
most definitive yet assessing the role of the cognitive
enhancers Bacopa and Pycnogenol on combined
cognitive and biological measures in elderly participants.
Improving the cognitive functioning of elderly citizens
will have significant benefits at the societal, economic
and personal levels. Cognitive capacity is strongly
correlated with performance in many occupations and
ameliorating the decline in fluid intelligence, memory and
reasoning will allow many elderly people to continue to
work and to continue to contribute to our society as
they age. Coupled with the large sample size, ARCLI is
one of the most definitive studies to explore the effects
of Bacopa and Pycnogenol on cognitive ageing. Results
from this study may help guide policies and preventative
health practices in the elderly.
AD: Alzheimers Disease; ANOVA: Analysis of Variance; APOE: Apolipoprotein
E; ANZCTR: Australia and New Zealand Clinical trials Registry; ARCLI:
Australian Research Council Longevity Intervention; BMI: Body Mass Index;
BP: Blood Pressure; CDR: Cognitive Drug Research; CRP: C Reactive Protein;
DRS: Mattis Dementia Rating Scale; FFQ: Food Frequency Questionnaire;
GDS: Geriatric Depression Scale; IQ: Intelligence Quotient; MBA: Multiple
Blood Analysis; MMSE: Mini Mental State Examination; NEO PI-R: NEO
Personality-Inventory Revised; POMS: Profile of Mood States; PWV: Pulse
Wave Velocity; Q: Questionnaire; RCT: Randomized, Controlled Trial; ROS:
Reactive Oxygen Species; RT: Reaction Time; SNP: Single Nucleotide
Polymorphisms; SUCCAB: Swinburne University Computerized Cognitive
Assessment battery; WASI: Wechsler Abbreviated Scale of Intelligence; WM:
The study is funded by an Australian Research Council Discovery grant to
Prof Stough, Scholey and Croft with co-funding from Horphag and Flordis
who are providing the Pycnogenol and Bacopa respectively. Mr. Pase
receives a Menzies Foundation Scholarship in Allied Health Sciences to work
on the ARCLI trial.
CS and AS conceived the study. CS, AS and KC were applicants for funding.
All authors were involved in designing the study and drafting the protocol.
All authors read and approved the final protocol.
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