Content uploaded by Andrew Scholey
Author content
All content in this area was uploaded by Andrew Scholey
Content may be subject to copyright.
Short-Term Study on the Effects of Rosemary on Cognitive Function
in an Elderly Population
Andrew Pengelly,
1
James Snow,
1
Simon Y. Mills,
1
Andrew Scholey,
2
Keith Wesnes,
2,3
and Leah Reeves Butler
1
1
Herbal Medicine Department, Tai Sophia Institute, Laurel, Maryland, USA.
2
NICM Centre for Neurocognition, Brain Sciences Institute, Swinburne University, Melbourne, Victoria, Australia.
3
United BioSource Corporation, Goring-on-Thames, United Kingdom.
ABSTRACT Rosemary (Rosmarinus officinalis L.) has traditional reputations that justify investigation for a potential role in
reducing widespread cognitive decline in the elderly. A randomized, placebo-controlled, double-blinded, repeated-measures cross-
over study was conducted to investigate possible acute effects of dried rosemary leaf powder on cognitive performance. Twenty-eight
older adults (mean age, 75 years) were tested using the Cognitive Drug Research computerized assessment system 1, 2.5, 4, and 6
hours following a placebo and four different doses of rosemary. Doses were counterbalanced, and there was a 7-day washout between
visits. There was a biphasic dose-dependent effect in measures of speed of memory: the lowest dose (750 mg) of rosemary had a
statistically significant beneficial effect compared with placebo (P=.01), whereas the highest dose (6,000 mg) had a significant
impairing effect (P<.01). There were significant deleterious effects on other measures of cognitive performance, although these were
less consistent. Speed of memory is a potentially useful predictor of cognitive function during aging. The positive effect of the dose
nearest normal culinary consumption points to the value of further work on effects of low doses over the longer term.
KEY WORDS: acute effects clinical trial cognitive memory rosemary Rosmarinus
INTRODUCTION
Reduced cognitive faculties are a frequent conse-
quence of aging and a major threat to quality of life.
Anticholinesterase and other drug treatments are available
for cognitive decline;
1
however, their potential cognitive
benefits are not necessarily apparent in older subjects,
and some such drugs have been shown to promote nega-
tive neurocognitive effects in this age group.
1,2
Traditional plant-based remedies have long-standing
reputations for supporting healthy aging, and recent inves-
tigations have examined the potential for cognitive en-
hancement of such medicines.
3–9
A recent meta-analysis of
13 randomized controlled trials into herbal interventions for
dementia concluded that herbal medicines were more ef-
fective than placebo and at least equivalent to conventional
therapies on common cognitive performance outcome
measures.
10
Additional studies have focused on cognitive
changes brought about by herbal intervention in healthy older
adults (e.g., for Bacopa monnieri,
11
Ginkgo biloba,
12–14
Centella asiatica,
15
and cranberry juice
16
). Several investi-
gations have been conducted into members of the mint
family (Lamiaceae),
17
including lemon balm (Melissa offi-
cinalis),
18,19
sage (Salvia officinalis,Salvia lavandulaefo-
lia),
20–22
lavender (Lavandula angustifolia),
23
and rosemary
(Rosmarinus officinalis).
23
Rosemary (R. officinalis L., Family Lamiaceae) is native
to the Mediterranean region, where the ancient Greeks re-
vered it for stimulating the brain and assisting memory;
24
Dioscorides wrote of rosemary: ‘‘the eating of its flower in a
preserve comforts the brain, the heart and the stomach;
sharpens understanding, restores lost memory, awakens the
mind, and in sum is a healthy remedy for various cold ail-
ments of the head and the stomach.’’ Rosemary has Gen-
erally Recognized as Safe status in the United States and is
widely used as a culinary herb. Extracts of rosemary and its
dried leaf are also available as ‘‘dietary supplements.’’
Rosemary contains an essential oil (0.6–2%) of varying
composition (three main chemotypes are found growing in
Europe). The major constituents of the essential oil are 1,8-
cineole, a-pinene, camphor, borneol, and carvacrol, but the
exact composition can vary between individual samples and
time of harvest.
25–27
Other constituents include phenolic
diterpenes, flavones, the caffeic acid derivative rosmarinic
acid, and the triterpene ursolic acid.
28,29
In experimental studies, rosemary extracts were shown to
possess potent radical scavenging activity.
26,30
The di-
terpenes carnosol and carnosic acid are thought to be the
major antioxidant components,
26,27
although antioxidant
properties have also been reported for several other
Manuscript received 7 January 2011. Revision accepted 15 June 2011.
Address correspondence to: Andrew Pengelly, Herbal Medicine Department, Tai Sophia
Institute, 7750 Montpelier Road, Laurel, MD 20723, USA, E-mail: apengelly@tai.edu
JOURNAL OF MEDICINAL FOOD
J Med Food 15 (1) 2012, 10–17
#Mary Ann Liebert, Inc. and Korean Society of Food Science and Nutrition
DOI: 10.1089/jmf.2011.0005
10
constituents, including rosmarinic acid.
31–34
In vitro studies
with rosemary extracts have demonstrated acetylcholines-
terase inhibition,
8,35
butyrylcholinesterase inhibition,
36
and
a protective effect on dopaminergic neurons.
37
Using mouse models an antidepressant effect of rosemary
has been identified, apparently mediated by an interaction
with the monoaminergic system.
38
There are antinociceptive
effects in animals
39
inhibited by naloxone pretreatment
40
—
suggesting interaction with the endogenous endorphin system,
as well as antispasmodic effects on tracheal smooth muscle.
41
There are few clinical studies on the effects of rosemary.
In a randomized study of 140 healthy young adults, inha-
lation of rosemary oil enhanced feeling of alertness and
cognitive functions as evaluated using the Cognitive Drug
Research (CDR) test battery used in the current study.
22
In a
separate study the aroma of rosemary oil increased perfor-
mance in exam students while increasing free radical
scavenging activity and reducing cortisol levels.
42
However,
to date there are no clinical studies on cognitive perfor-
mance following ingestion of rosemary.
MATERIALS AND METHODS
The current study was a randomized, placebo-controlled,
double-blinded, repeated-measures, crossover study inves-
tigating acute effects of dried rosemary (R. officinalis L.)
leaves on cognitive performance in older adults, using a
battery of tests provided by the CDR.
43
Because the acute
effects of rosemary were being explored, doses higher than
normally consumed in the diet were applied. Additionally,
the crude rosemary powder was used in a dietary formula-
tion rather than a pharmaceutical extract to retain the
pharmacokinetic profile of ordinary culinary consumption.
Subjects
Twenty-eight subjects (eight men, 20 women) were re-
cruited via local media and networking. They were non-
smokers between 65 and 90 years (mean, 75 years) in a stable
state of health with no confounding medications and able to
complete the computerized battery tests on laptop computers.
Ethical approval was obtained from the Institutional Review
Board of Tai Sophia Institute (Laurel, MD, USA). This study
complied with current guidelines for Good Clinical Practice
guidance issued by the U.S. Food and Drug Administration to
protect human subjects of research and the Ethical Principles
for Medical Research Involving Human Subjects adopted in
the World Medical Association Declaration of Helsinki.
Treatments
The test substance consisted of 100% powdered rosemary
(R. officinalis L.) originating from Turkey and supplied by
McCormick & Co. (Hunt Valley, MD, USA). Authentication
was performed by Dr. Arthur Tucker at Delaware State Uni-
versity (Dover, DE, USA) based on macro- and microscopic
features. Seven constituents were characterized and quantified
applying gas chromatographic and mass spectrometric meth-
ods modified from those of Razbors
ˇek et al.
44
Hydrodistillation
of the rosemary sample yielded 1.4% volatile oil, consisting of
1,8-cineole (0.57%), borneol (0.14%), and a-pinene (0.13%) as
the major components. In addition, key nonvolatile compounds
were quantified, including rosmarinic acid (1.45% wt/wt),
carnosic acid (1.73%), and ursolic acid (2.89%).
The powdered rosemary was added to a commercial to-
mato juice (Campbell’s [Camden, NJ, USA] low sodium).
Subjects on each study day received a single 16-ounce
(458-mL) drink of reduced sodium tomato juice containing
(in decreasing order of weight) water, tomato concentrate,
potassium chloride, vitamin C (ascorbic acid), citric acid, salt,
flavoring, and malic acid. Total oxygen radical absorbance
capacity per serving was calculated as 10,782 lmol of Trolox
equivalents, and the content of total phenolics was 299 mg of
gallic acid equivalents. Each 458 mL of juice additionally
contained one of the following doses of rosemary: (1) no
rosemary (placebo; see below); (2) 750mg of dried rosemary;
(3) 1,500mg of dried rosemary; (4) 3,000 mg of dried rose-
mary; or (5) 6,000 mg of dried rosemary. A third party pre-
pared, codified, and delivered the treatments to participants.
Masking was achieved by the use of opaque containers with
black drinking straws and by chilling the drink.
Placebo consisted of the tomato juice as described above.
To confound distinction further between the treated and
untreated tomato juice, each dose was co-administered with
colored methylcellulose-filled capsules. Subjects were in-
formed that these capsules could be part of the treatment.
Cognitive measures
A battery of tasks from the CDR System was adminis-
tered. Parallel forms of the tasks were performed at different
sessions to reduce practice effect on repeated assessment.
The information in all tasks was presented on the screen of a
notebook computer, and with the exception of the written
word recall tasks the responses were recorded via a response
module containing ‘‘NO’’ and ‘‘YES’’ buttons. The battery
took about 25 minutes to perform (Table 1 contains brief
descriptions [see, for example, Tildesley et al.
20
for de-
tails]). The individual task outcomes from the battery were
collapsed into five cognitive ‘‘factors,’’ as recommended by
CDR following their derivation by factor analysis
43
(Fig. 1).
Two of these factors concern attention: ‘‘power of atten-
tion’’ (sometimes called ‘‘speed of attention’’) reflects the
ability to focus attention, whereas continuity of attention (or
‘‘accuracy of attention’’) reflects the ability to sustain at-
tention. ‘‘Quality of working memory’’ reflects the ability to
successfully hold numeric and spatial information tempo-
rarily in working memory, whereas ‘‘quality of episodic
memory’’ reflects the ability to store, hold, and subsequently
retrieve verbal and non-verbal information in long-term
(episodic) memory. ‘‘Speed of memory’’ reflects the time
taken to successfully retrieve information from both work-
ing and episodic memory.
Mood measures
Mood was assessed using the Bond–Lader visual analog
scales.
45
These consist of 16 100-mm lines anchored by
ROSEMARY COGNITION STUDY 11
antonyms (e.g., ‘‘clearheaded–muzzy’’), which are com-
bined to derive three mood factors of alert, calm, and con-
tent. The Bond–Lader Visual Analogue Scales were
presented by computer.
Procedure
The tests were performed under experimenter supervision
on five separate 1-day treatment sessions every week for 5
weeks following a practice day. The order of intervention on
the five study visits was determined by random allocation.
Each study day comprised five identical testing sessions: a
pre-dose testing session to establish baseline performance
for that day, followed immediately by the allocated inter-
vention and assessments at 1, 2.5, 4, and 6 hours following
consumption. Subjects were asked to refrain from alcohol at
least 12 hours prior to assessments on these days.
Data treatment and statistics
Changes from baseline scores for the treatments were
computed for each cognitive measure, at each time point.
These data were subjected to a general linear mixed-model
analysis of covariance with terms fitted to the model for
treatment (6,000 mg, 3,000 mg, 1,500 mg, 750 mg, 0 mg),
day (Day 1, Day 2, Day 3, Day 4, and Day 5), visit (diff 1,
diff 2, diff 4, diff 6), treatment ·visit, and participant. A
‘‘repeated-measures’’ analysis of covariance was conducted
using SAS PROC MIXED (SAS Institute, Cary, NC, USA).
Using the baseline on each study day as a covariate allowed
control for differences between subjects. Statistical signifi-
cance was set at a value of P<.05, whereas P<.01 was set
as highly significant.
RESULTS
Of the total 28 participants who began the study, one was
asked to leave because of concerns about a preexisting
medical condition. There were no other dropouts.
There was a main effect of treatment for ‘‘speed of
memory’’ measures (F
4,96
=7.19, P<.0001) that was dose-
specific. At 750 mg there was a significant improvement
(P=.01), and at 6,000 mg there was a significant impairment
(P<.01), compared with placebo. All treatments including
placebo showed a significant impairment compared with
baseline except the 750-mg dose, which showed negligible
difference from baseline.
‘‘Continuity of attention’’ was significantly impaired at
1,500 (P<.001), 3,000 (P=.04), and 6,000 mg (P<.001)
doses, and ‘‘quality of working memory’’ was significantly
impaired at 750 (P=.02), 1,500 (P=.01), and 6,000 mg
(P=.01), in both cases compared with placebo. However, the
differences are much smaller when compared with baseline.
There were no effects for the ‘‘power of attention’’ and
‘‘quality of episodic secondary memory’’ scores (Fig. 2 and
Table 2).
For the self-ratings of mood and alertness, all scores in-
cluding placebo were reduced from baseline as the testing
day progressed. Of note was a significant improvement at
Table 1. Cognitive Drug Research Tests
Tests were administered in the following order:
Word Presentation: A list of words is presented for the subject to remember.
Immediate Word Recall: Immediately after the last word is presented, the subject is given 1 minute to write as many of the words as
possible on a sheet of paper.
Picture Presentation: A series of pictures for the subject to remember is presented.
Simple Reaction Time: The subject is instructed to press the ‘‘YES’’ response button, as quickly as possible, every time the word ‘‘YES’’
is presented.
Digit Vigilance: A target digit is pseudo-randomly selected and constantly displayed to the right of the screen. A series of digits is then
presented in the center of the screen. The subject is required to press the ‘‘YES’’ button as quickly as possible every time a digit in the
series matches the target digit.
Choice Reaction Time: The subject is required to respond to the words ‘‘YES’’ and ‘‘NO’’ as they appear by pressing the corresponding
button as quickly as possible.
Spatial Working Memory: A picture of a house is presented on the screen with four of the nine windows lit. The subject is asked to memorize
the position of the lit windows. For each of the subsequent presentations of the house, the subject is asked to decide whether or not the
single window that is lit had been lit in the original presentation. The subject responds by pressing the corresponding ‘‘YES’’ or ‘‘NO’’
button, as appropriate, as quickly as possible.
Numeric Working Memory: A series of digits is presented for the subject to hold in memory. This is followed by a series of probe digits,
for each of which the subject has to decide whether it had appeared in the original series and press the corresponding ‘‘YES’’ or ‘‘NO’’
response button as quickly as possible.
Delayed Word Recall: The subject is again given 1 minute to write as many of the words as possible in any order on a sheet of paper.
Word Recognition: The original words from Word Presentation plus distractor words are presented, one at a time, in a randomized order. For
each word, the subject is required to indicate whether he or she recognizes it from the original list of words by pressing the corresponding
‘‘YES’’ or ‘‘NO’’ button as quickly as possible.
Picture Recognition: The original pictures from Picture Presentation plus distractor pictures are presented, one at a time. For each picture,
the subject is required to indicate whether he or she recognizes it from the original series by pressing the corresponding ‘‘YES’’ or ‘‘NO’’
button as quickly as possible.
Bond-Lader Visual Analogue Scales of Mood and Alertness: For this computerized questionnaire scale, the subject is required to rate
how he or she feels ‘‘at this moment.’’
45
12 PENGELLY ET AL.
FIG. 1. Derivation of cognitive fac-
tors from the Cognitive Drug Research
battery outcomes.
FIG. 2. Effects of R. officinalis (rose-
mary [RO]) powder (750, 1,500, 3,000,
and 6,000 mg) and placebo on cogni-
tive factors derived from Cognitive
Drug Research battery scores. Mean
changes from baseline are shown for
(a) power of attention, (b) continuity
of attention, (c) speed of memory, (d)
working memory, and (e) secondary
memory.
13
750 mg in alertness (P=.01) compared with placebo,
whereas at 6,000 mg there was the opposite effect indicating
decreased alertness compared with placebo (P=.02). This
finding suggests a biphasic dose–response curve similar to
that observed for the speed of memory factor (Table 3).
The mixed analysis of covariance showed there was no
correlation between treatment and time in any of these
findings. A further analysis was carried out to explore
whether there was any global order effect. Some orders were
identified, but the counterbalancing ensured they did not
contribute to the study results.
There were no serious adverse events recorded in placebo
or treatment groups during the study.
DISCUSSION
This study clearly demonstrates significant dose-specific
effects of rosemary on ‘‘speed of memory’’ compared with
placebo: positive for the lowest dose (750 mg) but negative
at the highest dose tested (6,000 mg). Moreover, when
compared with baseline the 750-mg dose appears to counter
the impairments that occur under placebo, possibly due to
fatigue. The fact that subjects at this dose subjectively re-
ported significantly less impairment to their alertness com-
pared with placebo strengthens the findings, particularly as
there is research suggesting that mood is an underlying
driver of cognitive function.
46
Several rosemary doses produced impairment of the
‘‘continuity of attention’’ and ‘‘quality of working memory’’
factors, but none of these effects was dose specific. The
mechanisms underlying these effects are not known. How-
ever, the preparation is rich in bioactive constituents, in-
cluding the monoterpenoids a-pinene, 1,8-cineole, and
borneol. A recently characterized extract of S. officinalis
(sage) with both anticholinesterase and memory-enhancing
properties contained these same constituents.
46
Ad-
ditionally, ursolic acid, rosmarinic acid, and carnosic acid
found in rosemary are bioavailable and have characterized
physiological effects that may influence cognitive func-
tioning. The presence of multiple potentially psychoactive
components is also likely to underlie the complex dose–
response relationships observed in the current study.
47,48
Quality of working memory differed from speed of mem-
ory, which is interesting in light of evidence suggesting that
decreased processing speed is responsible for impaired
working memory and skill acquisition in older adults, possibly
contributing to age-related decline in overall intelligence.
49–53
Rodrı
´guez-Sa
´nchez et al.
53
cited many reports demonstrating
links between reduced speed of processing and cognitive
dysfunction with impaired declarative or working memory in
normal aging, traumatic brain injury, depression, and Par-
kinson’s disease. There are two functional components of
human working memory: short-term working memory and
long-term working memory. Short-term working memory
involves actively updating and manipulating representations,
switching and dividing attention between tasks, selection of
relevant information, and inhibition of irrelevant informa-
tion.
54–59
Short-term working memory also encodes infor-
mation so that this can be retrieved from long-term working
memory. If encoding speed is not rapid enough, a person may
lose information and not be able to retrieve memories from
long-term working memory,
60
with a possible overall mem-
ory deficit for both short and long term and a potential decline
in overall intelligence.
51,57
If decreased processing speed is
responsible for impaired working memory, skill acquisition,
and overall cognitive performance in older adults as is re-
inforced by other research,
49–51,61
then any potential to im-
prove such processing speed warrants attention. The present
study’s finding for improvements in speed of memory at the
Table 2. Composite Scores for Effects of R. officinalis
Powder on Five Cognitive Factors
Cognitive factor Dose Composite score* SE Pvalue
Power of attention
(milliseconds)
750 mg -18.493 10.650 .085
1,500 mg 3.818 10.225 .709
3,000 mg 6.902 10.917 .528
6,000 mg 3.657 10.534 .729
Continuity
of attention (score)
750 mg -1.016 0.643 .117
1,500 mg -2.230 0.618 <.001
3,000 mg -1.376 0.658 .039
6,000 mg -2.363 0.637 <.001
Speed of memory
(milliseconds)
750 mg -231.920 91.204 .012
1,500 mg -96.826 87.592 .271
3,000 mg 29.130 93.453 .755
6,000 mg 253.830 91.390 .006
Quality of working
memory (score)
750 mg -0.157 0.065 .018
1,500 mg -0.167 0.063 .009
3,000 mg -0.098 0.067 .144
6,000 mg -0.169 0.065 .011
Quality of episodic
memory (score)
750 mg 1.998 6.271 .750
1,500 mg -9.140 5.992 .131
3,000 mg -8.567 6.240 .174
6,000 mg -1.695 5.928 .775
Means averaged across time points are presented with SEs and Pvalues
associated with main effects of treatment.
*All scores are differences from placebo.
Table 3. Acute Cognitive Effects of R. officinalis
Powder on Bond–Lader Mood Scale Factor Scores
Measure Dose Score SE Pvalue
Alert 750 mg 4.061 1.619 .014
1,500 mg 0.017 1.553 .991
3,000 mg -2.018 1.66 .227
6,000 mg -3.689 1.574 .021
Content 750 mg 1.267 1.238 .309
1,500 mg 1.525 1.878 .202
3,000 mg 0.546 1.269 .668
6,000 mg -0.294 1.204 .807
Calm 750 mg 2.779 2.207 .211
1,500 mg 1.761 2.118 .408
3,000 mg 2.499 2.262 .272
6,000 mg 3.553 2.149 .105
The values represent mean change from placebo for each treatment.
14 PENGELLY ET AL.
750-mg dosage merits further investigation at this and lower
dosage levels.
Limitations of the study
The activity of the placebo dose is notable in all the re-
sults. The tomato juice vehicle was chosen as a means of
delivering relatively high doses of crude rosemary powder in
culinary form. However, the results suggest the combination
of fluid consumption and constituents within the tomato juice
were unexpectedly active. There is evidence that fluid intake
may impair or improve short-term cognitive performance.
62
The population examined was not typical of the elderly
U.S. population, with education levels as well as baseline
scores on the cognitive tests above the average. When cou-
pled with the documented tendency for ‘‘participant self-
selection,’’ where volunteers in studies of this nature are
likely to be healthier, more socioeconomically advantaged,
and more highly motivated compared with their peers, the
application of the results to broader populations is reduced.
63
The short-term nature of the study does not address the
real world impact of regular consumption of rosemary. It is
not known whether regular consumption will lead to brain
adaptation or cumulative benefits. Only longer-term studies
will clarify whether regular consumption of rosemary en-
hances, diminishes, or shows no variation from the short-
term effects on cognition.
Finally, several participants were able to detect taste
differences. Subsequent analyses, however, showed no
consistent impact of this detection, and the addition of
placebo capsules to the food-based preparation may have
countered this effect.
In conclusion, rosemary powder at the dose nearest nor-
mal culinary consumption demonstrated positive effects on
speed of memory—a potentially useful predictor of cogni-
tive function during aging. The result points to the value of
future studies on effects of low doses of rosemary on
memory and cognition over the longer term.
ACKNOWLEDGMENTS
The authors are grateful to McCormick Science Institute
for their sponsorship of this study and supplying and ana-
lyzing the rosemary and for Cognitive Drug Research for the
use of their battery and materials and for data processing.
Further valuable help in analyzing the results was provided
by Dr. Charles Clark from Exeter, United Kingdom.
AUTHOR DISCLOSURE STATEMENT
K.W. is an employee of United BioSource Corporation.
A.P., J.S., S.Y.M., A.S., and L.R.B. declare no competing
financial interests exist.
REFERENCES
1. Beuzen J-N, Taylor N, Wesnes K, Wood A: A comparison of the
effects of alanzapine, haloperidol and placebo on cognitive and
psychomotor functions in healthy elderly volunteers. J Psycho-
pharmacol 1999;13:152–158.
2. Brooks JO, Hoblyn JC: Neuocognitive costs and benefits of
psychotic medications in older adults. J Geriatr Psychiatry
Neurol 2007;20:199–214.
3. Sorrensen H, Sonne J: A double-masked study on the effects of
ginseng on cognitive function. Curr Ther Res 1996;57:959–968.
4. Ellis KA, Stough C, Vitetta L, Heinrich K, Nathan PJ: An in-
vestigation into the acute nootropic effects of Hypericum per-
foratum L. (St. John’s wort) in healthy human volunteers. Behav
Psychol 2001;12:173–182.
5. Howes MJ, Houghton PJ: Plants used in Chinese and Indian
traditional medicine for improvement of memory and cognitive
function. Pharmacol Biochem Behav 2003;75:513–527.
6. Kennedy DO, Scholey AB, Wesnes KA: Differential, dose-de-
pendent changes in cognitive performance and mood following
acute administration of ginseng to healthy young volunteers. Nutr
Neurosci 2001;4:295–310.
7. Kennedy DO, Scholey AB, Wesnes KA: Modulation of cognition
and mood following administration of single doses of Ginkgo
biloba, ginseng and a ginkgo/ginseng combination to healthy
young adults. Physiol Behav 2002;75:1–13.
8. Howes MJ, Perry NSL, Houghton PJ: Plants with traditional uses
and activities, relevant to the management of Alzheimer’s dis-
ease and other cognitive disorders. Phytother Res 2003;17:1–18.
9. Perry EK, Pickering AT, Wang WW, Houghton P, Perry NS:
Medicinal plants and Alzheimer’s disease: integrating ethnobo-
tanical and contemporary scientific evidence. J Altern Comple-
ment Med 1998;4:419–428.
10. May BH, Xue CCL, Yang AWH, Zhang AL, Owens MD, Head
R, Cobiac L, Li CG, Hugel H, Story DF: Herbal medicine for
dementia. Phytother Res 2009;23:447–459.
11. Calabrese C, Gregory WL, Leo M, Kraemer D, Bone K, Oken B:
Effects of a standardized Bacopa monnieri extract on cognitive
performance, anxiety, and depression in the elderly: a random-
ized, double-blind, placebo-controlled trial. J Altern Complement
Med 2008;14:707–713.
12. Mix J, Crews W Jr: A double-blind, placebo-controlled, ran-
domized trial of Ginkgo biloba extract EGb761 in a sample of
cognitively intact older adults: neuropsychological findings. Hum
Psychopharmacol Clin Exp 2002;16:267–277.
13. Snitz BE, O’Meara ES, Carlson MC, Arnold AM, Ives DG, Rapp
SR, Saxton J, Lopez OL, Dunn LO, Sink KM, DeKosky ST:
Ginkgo biloba for preventing cognitive decline in older adults.
JAMA 2009;302:2663–2670.
14. Wesnes KA, Ward T, McGinty A, Petrini O: The memory en-
hancing effects of a Ginkgo biloba/Panax ginseng combination
in healthy middle aged volunteers. Psychopharmacology 2000;
152:353–361.
15. Wattanathorn J, Mator L, Muchimapura S, Tongun T, Pasuriwong
O, Piyawatkul N, Yimtae K, Sripandikulchai B, Singkhoraad:
Positive modulation of cognition and mood in the healthy elderly
volunteer following the administration of Centella asiatica.
J Ethnopharmacol 2008;116:325–332.
16. Crews WD Jr, Harrison DW, Griffen ML, Addison K, Yount
AM, Giovenco MA, Hazell JA: Double-blinded, placebo con-
trolled, randomized trial of the neuropsychologic efficacy of
cranberry juice in a sample of cognitively intact older adults:
pilot study findings. J Altern Complement Med 2005;11:305–
309.
ROSEMARY COGNITION STUDY 15
17. Kennedy DO, Scholey AB: The psychopharmacology of Euro-
pean herbs with cognition-enhancing properties. Curr Pharm Des
2006;12:4613–4623.
18. Kennedy DO, Scholey AB, Tildesley NT, Perry EK, Wesnes KA:
Modulation of mood and cognitive performance following acute
administration of Melissa officinalis (lemon balm). Pharmacol
Biochem Behav 2002;72:953–964.
19. Kennedy DO, Wake G, Savelev S, Tildesley NT, Perry EK,
Wesnes KA, Scholey AB: Modulation of mood and cognitive
performance following acute administration of single doses of
Melissa officinalis (Lemon balm) with human CNS nicotinic and
muscarinic receptor-binding properties. Neuropsychopharma-
cology 2003;28:1871–1881.
20. Tildesley NTJ, Kennedy DO, Perry EK, Ballard CG, Wesnes
KA, Scholey AB: Positive modulation of mood and cognitive
performance following acute doses of Salvia lavendulaefolia
essential oil to healthy young volunteers. Physiol Behav 2005;85:
699–709.
21. Scholey AB, Tildesley NTJ, Ballard CG, Wesnes KA, Tasker
A, Perry EK, Kennedy DO: An extract of Salvia (sage) with
anticholinesterase properties improves memory and attention in
healthy older volunteers. Psychopharmacology 2008;198:127–
139.
22. Kennedy D, Dodd F, Robertson B, Okello E, Reay J, Scholey A,
Haskell C: Monoterpenoid extract of sage (Salvia lavandulae-
folia) with cholinesterase inhibiting properties improves
cognitive performance and mood in healthy adults. J Psycho-
pharmacol 2011;25:1088–1100.
23. Moss M, Cook J, Wesnes K, Duckett P: Aromas of rosemary and
lavender essential oils differentially affect cognition and mood in
health adults. Int J Neurosci 2003;113:15–38.
24. Small E: Culinary Herbs, 2nd ed. NRC Research Press, Ottawa,
2006, p. 769.
25. Tucker AO, Debaggio T: The Encyclopedia of Herbs. Timber
Press, Portland, OR, 2009, p. 434.
26. Ganena AK, Hense H, Sma
ˆnia Junior A, de Souza SM: Rosemary
(Rosmarinus officinalis)—a study of the composition, antioxidant and
antimicrobial activities of extracts obtained with supercritical carbon
dioxide. Cienc Tecnol Aliment Campinas 2008;28:463–469.
27. Baydar H, Ozkan G, Erbas S, Altindal D: Yield, chemical
composition and antioxidant properties of extracts and essential
oils of sage and rosemary depending on seasonal variations. Acta
Hort 2009;826:383–389.
28. Bisset NG, ed.: Herbal Drugs and Phytopharmaceuticals. CRC
Press, Boca Raton, FL, 1994, pp. 428–430.
29. Ho C-T, Huang M-T, Lou Y-R, Ma W, Shao Y, Wei G-J,
Wang M, Chin C-K: Antioxidant and antitumor activity in
rosemary leaves. In: Phytochemicals and Phytopharmaceuticals
(Shadihi F, Ho CH, eds.) AOCS Press, Champaign, IL, 2000,
pp. 296–300.
30. Grazma-Michalowski A, Abramowski Z, Jovel E, Hes M: Anti-
oxidant potential of herb extracts and impact on HepG2 cells
viability. Acta Sci Pol Technol Aliment 2008;7:61–72.
31. Schwarz K, Ternes W: Antioxidative constituents of Rosmarinus
officinalis and Salvia officinalis. II. Isolation of carnosic acid and
formation of other phenolic diterpenes. Z Lebensm Unters Forsch
1992;195:99–103.
32. Haraguchi H, Saito T, Okamura N, Yagi A: Inhibition of lipid
peroxidation and superoxide generation by diterpenoids from
Rosmarinus officinalis.Planta Med 1995;61:333–336.
33. Zeng HH, Tu PF, Zhou K, Wang H, Wang BH, Lu JF: Anti-
oxidant properties of phenolic diterpenes from Rosmarinus offi-
cinalis.Acta Pharmacol Sin 2001;22:1094–1098.
34. Dastmalchi K, Ollilainen V, Lackman P, Genna
¨s GB, Dorman
HJ, Ja
¨rvinen PP, Yli-Kauhaluoma J, Hiltunen R: Acet-
ylcholinesterase inhibitory guided fractionation of Melissa offi-
cinalis L. Bioorg Med Chem 2009;15:867–871.
35. Adsersen A, Gauguin B, Gudiksen L, Ja
¨ger AK: Screening of
plants used in Danish folk medicine to treat memory dysfunction
for acetylcholinesterase inhibitory activity. J Ethnopharmacol
2006;104:418–422.
36. Orhan I, Aslan S, Kartal M, Sener B, Basar HC: Inhibitory effect
of Turkish Rosmarinus officinalis on acetylcholinesterase and
butyrylcholinesterase enzymes. Food Chem 2008;108:663–668.
37. Kim SJ, Kim JS, Cho HS, Lee HJ, Kim SY, Kim S, Lee SY,
Chun HS: Carnosol, a component of rosemary (Rosmarinus of-
ficinalis L.) protects nigral dopaminergic neuronal cells. Neu-
roreport 2006;17:1729–1733.
38. Machado DG, Bettio LE, Cunha MP, Capra JC, Dalmarco JB,
Pizzolatti MG, Rodrigues AL: Antidepressant-like effect of the
extract of Rosmarinus officinalis in mice: involvement of the
monoaminergic system. Prog Neuropsychopharmacol Biol Psy-
chiatry 2009;33:642–650.
39. Gonza
´lez-Trujano ME, Pen
˜a EI, Martı
´nez AL, Moreno J, Gue-
vara-Fefer P, De
´ciga-Campos M, Lo
´pez-Mun
˜oz FJ: Evaluation
of the antinociceptive effect of Rosmarinus officinalis L. using
three different experimental models in rodents. J Ethnopharma-
col 2007;111:476–482.
40. Hosseinzadeh H, Nourbakhsh M: Effect of Rosmarinus officinalis
L. aerial parts extract on morphine withdrawal syndrome in mice.
Phytother Res 2003;17:938–41.
41. Aqel MB: Relaxant effect of the volatile oil of Rosmarinus officinalis
on tracheal smooth muscle. J Ethnopharmacol 1991;33:57–62.
42. McCaffrey R, Thomas DJ, Kinzelman AO: The effects of lav-
ender and rosemary essential oils on test-taking anxiety among
graduate nursing students. Holist Nurs Pract 2009;23:88–93
43. Wesnes K: Assessing change in cognitive function in dementia:
the relative utilities of the Alzheimer’s Disease Assessment
Scale-Cognitive Subscale and the Cognitive Drug Research
system. Neurodegener Dis 2008;5:261–263.
44. Razbors
ˇek MI, Von
cina DB, Dole
cek V, Von
cina E: Determina-
tion of major phenolic acids, phenolic diterpenes and triterpenes in
rosemary (Rosmarinus officinalis L.) by gas chromatography and
mass spectrometry. Acta Chim Slov 2007;54:60–67.
45. Bond A, Lader M: The use of analogue scales in rating subjective
feelings. Br J Psychol 1974;47:211–218.
46. Grandholm A-C, Bogor H, Emborg ME: Mood, memory and
movement: an age-related neurodegenerative complex? Curr
Aging Sci 2008;2:133–139.
47. Scholey A, Stough C: Neurocognitive effects of herbal extracts.
In: Lifetime Nutritional Influences on Cognition, Behaviour and
Psychiatric Illness (Benton D, ed.). Woodhead Publishing,
Cambridge, United Kingdom, 2011.
48. Scholey A, Kennedy D, Wesnes K: The psychopharmacology of
herbal extracts: issues and challenges. Psychopharmacology
2005;179:705–707.
49. Salthouse TA: The processing-speed theory of adult age differ-
ences in cognition. Psychol Rev 1996;103:403–428.
50. Craik FIM, Salthouse TA, eds.: The Handbook of Aging and Cog-
nition, 2nd ed. Lawrence Erlbaum Associates, Mahwah, NJ, 2000.
16 PENGELLY ET AL.
51. Fry A, Hale S: Processing speed, working memory, and fluid
intelligence: evidence for a developmental cascade, 4. Psychol
Sci 2006;7:237–241.
52. Rypma B, Berger JS, Prabhakaran V, Bly BM, Kimberg DY,
Biswal BB, D’Esposito M: Neural correlates of cognitive effi-
ciency. NeuroImage 2006;33:969–979.
53. Rodrı
´guez-Sa
´nchez JM, Crespo-Facorro B, Gonza
´lez-Blanch C,
Perez-Iglesias R, Va
´zquez- Barquero JL: Cognitive dysfunction
in first-episode psychosis: the processing speed hypothesis. Br J
Psychiatry Suppl 2007;191:s107–s110.
54. Baddeley AD: Working Memory. Oxford University Press, Ox-
ford, United Kingdom, 1986.
55. Baddeley AD: Exploring the central executive. Q J Exp Psychol
1996;49A:5–28.
56. Baddeley AD: The Oxford Book of Memory. Oxford University
Press, Oxford, United Kingdom, 2000, pp. 77–88.
57. Miyake A, Shah P, eds.: Models of Working Memory: Mechan-
isms of Active Maintenance and Executive Control. Cambridge
University Press, New York, 1999, pp. 103–126.
58. Repov G, Baddeley AD: The multi-component model of working
memory: explorations in experimental cognitive psychology.
Neuroscience 2006;139:5–21.
59. Cowan N: The magical number 4 in short-term memory: a re-
consideration of mental storage capacity. Behav Brain Sci 2001;
24: 87–114.
60. Oulasvirta A, Saariluoma P: Long-term working memory and
interrupting messages in human-computer interaction 1. Behav
Inform Technol 2004;23:53–64.
61. Maylor EA: Age and ageing. In: Age-Related Changes in
Memory ( Johnson M, ed.). Cambridge University Press, Cam-
bridge, United Kingdom, 2005, pp. 202–203.
62. Rogers PJ, Kainth A, Smit HJ: A drink of water can improve or
impair mental performance depending on small differences in
thirst. Appetite 2001;36:57–58.
63. Rabbitt P: Cognitive changes across the lifespan. In: Age-
Related Changes in Memory ( Johnson M, ed.). Cambridge
University Press, Cambridge, United Kingdom, 2005, pp.
190–191.
ROSEMARY COGNITION STUDY 17
