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Nutrients 2014, 6, 4032-4042; doi:10.3390/nu6104032
Green Tea Consumption Affects Cognitive Dysfunction in the
Elderly: A Pilot Study
Kazuki Ide 1, Hiroshi Yamada 1,*, Norikata Takuma 2, Mijong Park 1, Noriko Wakamiya 1,
Junpei Nakase 3, Yuuichi Ukawa 3 and Yuko M. Sagesaka 3
1 Department of Drug Evaluation and Informatics, Graduate School of Pharmaceutical Sciences,
University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan;
E-Mails: email@example.com (K.I.); firstname.lastname@example.org (M.P.);
m08129@ u-shizuoka-ken.ac.jp (N.W.)
2 White Cross Nursing Home, 2-26-1 Suwa-cho, Higashimurayama, Tokyo 189-0021, Japan;
3 Central Research Institute, ITO EN, Ltd., 21 Mekami, Makinohara, Shizuoka 421-0516, Japan;
E-Mails: email@example.com (J.N.); firstname.lastname@example.org (Y.U.);
* Author to whom correspondence should be addressed; E-Mail: email@example.com;
Received: 10 May 2014; in revised form: 14 July 2014 / Accepted: 19 September 2014 /
Published: 29 September 2014
Abstract: Green tea is known to have various health benefits for humans. However, the
effect of green tea consumption on cognitive dysfunction remains to be clinically verified.
We conducted a clinical study to investigate the effects of green tea consumption on
cognitive dysfunction. Twelve elderly nursing home residents with cognitive dysfunction
(Mini-Mental State Examination Japanese version (MMSE-J) score: <28) participated in the
study (2 men, 10 women; mean age, 88 years). The participants consumed green tea powder
2 g/day for 3 months. After three months of green tea consumption, the participants’
MMSE-J scores were significantly improved (before, 15.3 ± 7.7; after, 17.0 ± 8.2; p = 0.03).
This result suggests that green tea consumption may be effective in improving cognitive
function or reducing the progression of cognitive dysfunction; however, long-term
large-scale controlled studies are needed to further clarify the effect.
Keywords: green tea; oral administration; cognitive function; elderly
Nutrients 2014, 6 4033
In rapidly aging societies around the world, the number of patients with cognitive dysfunction,
particularly dementia, is gradually increasing . Dementia affects 5.4% of people over 65 years
of age worldwide, and its prevalence increases with age . There are several pharmaceutical and
non-pharmaceutical treatments for dementia; however, thus far, no fundamental curative therapy has
been established [3,4].
Green tea, one of the commonly consumed beverages in Asian countries, is known to have various
health benefits [5–7]. A number of experimental studies in vitro and in vivo have shown the
neuroprotective effects of green tea and its components, such as catechins and theanine [8–11].
Anti-oxidative and anti-inflammatory effects of these components have been reported [10–12], and such
effects may contribute to neuroprotection. Regarding cognitive function, catechins have been reported
to improve performance on cognition tests in rodent models of dementia, such as the Morris water maze,
probe test, and passive avoidance test . In mice, theanine has also been shown to attenuate memory
impairment induced by amyloid protein, an Alzheimer’s disease trigger protein .
Furthermore, several human epidemiological studies have shown a relationship between tea
consumption and cognitive function [13–18]. One study showed a negative association between
green tea consumption and the prevalence of cognitive impairment in elderly individuals over 70 years
old . Similar negative association has also been reported in other observational studies on tea
consumption [14–16,18]. These studies suggest that tea consumption effects cognitive function; however,
only limited interventional studies have been reported, and these effects remain to be clinically
verified [19,20]. One interventional study used a supplement called LGNC-07 containing 1440 mg green
tea extract and 240 mg theanine as a daily dose . It should be noted that LGNC-07 is a green-tea-
based supplement, not green tea as it is typically drunk, thus, it is important to also study the effect of
ordinary daily green tea consumption patterns on cognitive function.
In addition to the effect of green tea consumption on cognitive function, several studies have shown
that it also reduces the risk of developing hypertension  and lowers both total cholesterol (TC)
concentration and low density lipoprotein cholesterol (LDL-C) concentration in adults . Clinical
significance of these effects is still inconclusive; however, hypertension and dyslipidemia are risk factors
for atherosclerosis [23,24], and atherosclerosis is in turn related to cognitive dysfunction. Therefore,
green tea consumption may also reduce the progression of cognitive dysfunction indirectly by reducing
the effect of these related health problems on atherosclerosis.
Based on this previous research, we conducted a clinical study to investigate the effects of green tea
consumption on cognitive dysfunction and atherosclerotic risk factors in the elderly.
Nutrients 2014, 6 4034
2. Experimental Section
This study was conducted from July to September 2012 at the White Cross Nursing Home in Higashi-
Murayama, Japan. Recruitment was performed at the nursing home by posters. Fifteen elderly residents
with cognitive impairment were enrolled. Inclusion criteria were as follows: (1) >65 years of age; (2)
ability to orally ingest green tea powder; (3) no consumption of supplements with antioxidant effects
(vitamins E, C, and A, and β-carotene) during the study period; and (4) a Mini-Mental State Examination-
Japanese version (MMSE-J) score of <28 . Exclusion criteria were: (1) tea allergy; (2) severe cardiac,
respiratory, hepatic, or renal dysfunction; and (3) severe anemia. The diagnoses of the patients were
simply taken from the medical records at White Cross Hospital in Higashi-Murayama, Japan.
Written informed consent was obtained from both the subjects and their caregivers prior to enrollment.
The study protocol was approved by the Ethics Committee of the University of Shizuoka (No. 23-27,
approved on 11 May, 2012) and conducted in accordance with the Declaration of Helsinki. This pilot
study was registered with Clinical Trials.gov (NCT 01594086).
2.2. Study Design
The following baseline characteristics of subjects were recorded: age, sex, underlying diseases,
complications, medication, alcohol consumption, smoking habits, tea or supplement consumption habits,
activity of daily living, and brain magnetic resonance imaging (MRI) or computed tomography
The subjects were asked to consume green tea powder (2 g/day, containing 227 mg catechins and
42 mg theanine, manufactured by ITO EN Ltd. (Tokyo, Japan)) during meals for a period of 3 months.
The consumption of other supplements that could have antioxidant effects was prohibited during the
intervention period and for a seven-day washout period prior to the start of the intervention. Subjects
were advised to maintain their customary intake of home-brewed green tea or tea beverages during the
study period. The caregiving staff at the nursing home kept a diary for each subject in which they
recorded the daily intake of green tea powder, the amount of home-brewed green tea or tea beverages
consumed each day, any changes in the health of subjects or in the administration of medication, and the
occurrence of any adverse events.
MMSE-J tests were performed to assess the cognitive function of subjects. In addition, the following
data was collected: blood pressure; serum lipid levels, including TC, LDL-C, HDL-C, and triglycerides;
and blood glucose levels. All tests were performed at baseline and again after three months of green
2.3. Statistical Analysis
Changes in MMSE-J scores, including scores for specific cognitive domains, as well as clinical and
laboratory values obtained at baseline and three months after the start of green tea consumption were
determined by paired t-test or Wilcoxon signed-rank test. Statistical significance was set at p < 0.05. All
Nutrients 2014, 6 4035
statistical procedures were performed with IBM SPSS version 20.0 for Windows (IBM Corp., Armonk,
A total of 15 nursing home elderly residents and their caregivers gave written informed consent, and
were assessed for eligibility. One resident was excluded according to the exclusion criteria. Two
residents were excluded from the study after it had begun due to the retracting of their consent, so it was
not possible to obtain intervention data for these individuals. A total of 12 subjects (2 men,
10 women) completed the study. During the study period, a subject was hospitalized due to a hip fracture
but resumed participation 36 days after the initial enrollment. The mean age of subjects was
88 ± 7.6 (range, 70–98) years; eight subjects had vascular dementia, three had Alzheimer’s disease and
one had dementia with Lewy body. The characteristics of subjects are reported in Table 1. The
MMSE-J score distribution of the subjects prior to the intervention was as follows: 24–27 (mild cognitive
impairment (MCI)), two subjects (16.7%); 10–23 (mild and moderate dementia), six subjects (50.0%);
and 0–9 (severe dementia), four subjects (33.3%). Adherence to the green tea powder consumption
protocol was 99.7%.
Table 1. Clinical characteristics of study subjects.
Number of subjects 12
Age, mean ± SD (range) 88 ± 7.6 (70–98)
Sex, n (%)
Men 2 (16.7)
Women 10 (83.3)
Underlying disease, n (%)
Alzheimer’s disease 3 (25.0)
Vascular dementia 8 (66.7)
Dementia with Lewy bodies 1 (8.3)
MMSE-J score, n (%)
24–27 (MCI) 2 (16.7)
10–23 (mild to moderate) 6 (50.0)
0–9 (severe) 4 (33.3)
Complication a, n (%)
Hypertension 8 (66.7)
Diabetes 2 (16.7)
Hyperuricemia 1 (8.3)
Concomitant drug a, n (%)
Antihypertensive drug 8 (66.7)
Drug for hyperuricemia 2 (16.7)
Antidiabetic drug 1 (8.3)
Drug for dementia 1 (8.3)
Activities of daily living
Independence 0 (0.0)
Some assistance is necessary 12 (100)
Nutrients 2014, 6 4036
Table 1. Cont.
Usual tea consumption
Green tea, n (%) 12 (100)
Mean ± SD, mL/day 680 ± 229.8
Others b, n (%) 8 (66.7)
Mean ± SD, mL/day 85 ± 63.7
Alcohol use, n (%) 0 (0.0)
Smoking, n (%) 2 (16.7)
Dietary supplements, n (%) 0 (0.0)
MMSE-J, Mini-Mental State Examination Japanese version; MCI, Mild cognitive impairment. a More than one
choice was possible, b black tea or oolong tea.
Changes in MMSE-J scores before and after the intervention are shown in Table 2. Total MMSE-J
scores (mean ± SD) taken at baseline were significantly improved after three months of green tea
consumption (before, 15.3 ± 7.7; after, 17.0 ± 8.2; p = 0.03). In terms of specific cognitive domains, the
baseline scores for short-term memory (registration and recall) were significantly improved after the
intervention (before, 2.0 ± 1.8; after, 3.2 ± 1.8; p = 0.01) (Table 2).
In post hoc analysis for vascular dementia (n = 8), the MMSE-J scores (mean ± SD) were significantly
improved after the intervention (before, 18.4 ± 6.5; after, 20.6 ± 6.7; p = 0.03), and short-term memory
were also improved significantly (before, 2.6 ± 1.6; after, 4.0 ± 1.2; p = 0.04) (Table 2).
Table 2. MMSE-J scores before and after 3 months of green tea consumption.
Cognitive Function (MMSE-J Score) Green Tea Consumption (2 g/day)
Before After p Value
All subjects (n = 12)
Total MMSE-J score (max, 30) 15.3 ± 7.7 17.0 ± 8.2 0.03 t
Orientation (max, 10) 4.2 ± 3.1 4.3 ± 3.9 0.96 w
Short-term memory (max, 6) 2.0 ± 1.8 3.2 ± 1.8 0.01 t
Attention and calculation (max, 5) 2.1 ± 2.0 2.0 ± 2.3 0.91 w
Language (max, 8) 6.7 ± 1.7 6.9 ± 1.4 0.46 w
Visual construction (max, 1) 0.4 ± 0.5 0.7 ± 0.5 0.08 w
Vascular dementia (n = 8)
Total MMSE-J score (max, 30) 18.4 ± 6.5 20.6 ± 6.7 0.03 t
Orientation (max, 10) 5.1 ± 3.3 5.8 ± 3.8 0.11 t
Short-term memory (max, 6) 2.6 ± 1.6 4.0 ± 1.2 0.04 w
Attention and calculation (max, 5) 2.8 ± 1.9 2.5 ± 2.3 0.68 w
Language (max, 8) 7.4 ± 0.9 7.5 ± 0.9 0.32 w
Visual construction (max, 1) 0.5 ± 0.5 0.8 ± 0.5 0.16 w
Stratified analysis at each stages of cognitive dysfunction
Total MMSE-J score (max 30)
MCI (n = 2) 26.5 ± 0.7 29.0 ± 1.4 0.34 t
Mild to moderate (n = 6) 17.3 ± 3.7 18.8 ± 4.3 0.19 t
Severe (n = 4) 6.8 ± 1.7 8.3 ± 3.4 0.32 t
Values: Mean ± SD. Each p value was calculated using the following statistical method: t paired t-test, w Wilcoxon
signed-rank test. MMSE-J, Mini-Mental State Examination Japanese version; MCI, Mild cognitive impairment.
Nutrients 2014, 6 4037
After three months of green tea consumption, the triglyceride (TG) levels of subjects were
significantly lower than those measured at baseline (124 ± 80 mg/dL vs 103 ± 57 mg/dL; p = 0.04).
However, blood pressure, lipid profiles (TC, LDL-C, and high density lipoprotein cholesterol (HDL-C)),
and blood glucose levels were not significantly different (Table 3).
No serious adverse events associated with green tea consumption were observed during the
Table 3. Values of atherosclerotic factors before and after 3 months of green tea consumption.
Atherosclerotic factor Green Tea Consumption (2 g/day)
Before After p Value
All subjects (n = 12)
SBP (mmHg) 119 ± 19 126 ± 19 0.32 t
DBP (mmHg) 65 ± 13 70 ± 12 0.19 t
Serum lipid levels
TC (mg/dL) 190 ± 33 189 ± 28 0.84 t
HDL-C (mg/dL) 47 ± 18 48 ± 16 0.78 t
LDL-C (mg/dL) 112 ± 24 112 ± 27 0.97 t
TG (mg/dL) 124 ± 80 103 ± 57 0.04 w
Blood glucose levels
FPG (mg/dL) 124 ± 52 124 ± 38 0.86 w
HbA1c (%) 5.3 ± 0.6 5.2 ± 0.6 0.14 w
Values: Mean±SD. Each p value was calculated using the following statistical method: t paired t-test,
w Wilcoxon signed-rank test. SBP, Systolic blood pressure; DBP, Diastolic blood pressure; TC, total
cholesterol; HDL-C, high density lipoprotein cholesterol; LDL-C, low density lipoprotein cholesterol;
TG, Triglyceride; FPG, fasting plasma glucose; HbA1c: hemoglobin A1c.
In this pilot study conducted to investigate the effect of green tea consumption on cognitive
dysfunction and atherosclerotic risk factors in the elderly, we found that three months of green tea
consumption improved cognitive dysfunction based on MMSE-J score changes. Among MMSE-J
domains, the short-term memory domain was especially improved. These results support the findings of
previous epidemiological studies, and additionally demonstrate that green tea improves cognitive
function or reduces the progression of cognitive dysfunction even at the relatively low catechin and
theanine concentrations that can be obtained from ordinary levels of daily green tea intake. The green
tea powder used as a daily dose in this study contained as its main bioactive components 227 mg of
catechins and 42 mg of theanine, concentrations that are approximately equal to two to four cups of
bottled or home-brewed green tea.
The effect on cognitive function estimated by MMSE-J in this study may be partially explained in
terms of basic studies on the bioactive components of green tea, such as catechins and theanine. The
anti-oxidative and anti-inflammatory properties of these components [10–12] may have contributed to
the effect of green tea consumption on cognitive function. In addition to these properties, recent findings
have suggested that green tea may exert its neuroprotective effect through a variety of different
Nutrients 2014, 6 4038
mechanisms, including: tea polyphenols inhibiting acetylcholinesterase, which is a target for
Alzheimer’s disease medications ; green tea extract regulating the secretion of stress hormones such
as corticosterone, which is related to cognitive function ; and L-theanine modulating serotoninergic
[28–30], dopaminergic , and GABAergic  neurotransmission in brain. In particular, research on
acetylcholinesterase inhibition has shown that tea polyphenols, including catechins and theanine, also
blunted scopolamine-induced learning and memory impairment in model mice . In addition, other
ingredients, such as caffeine, might also be related to the improvement of MMSE-J scores by alerting
influence . In human, neural modulation related to cognitive function by green tea consumption have
been largely uncertain. However, recently, an enhancement of parieto-frontal connectivity by green tea
consumption was reported . Parieto-frontal connectivity contributes working memory processing;
therefore, it might be related in part to the effect of green tea on the improvement of MMSE-J score.
Post hoc analysis of vascular dementia data (n = 8) showed that total MMSE-J scores and short-term
memory domain scores were significantly improved after three months of green tea consumption.
Vascular dementia, the second most common type of dementia after Alzheimer’s disease, is
characterized by cognitive deficit of cerebrovascular origin. Our results indicate that green tea has
potential as a neuroprotective agent, especially for vascular dementia.
Individual MMSE-J scores tended to improve slightly regardless of the severity of cognitive
dysfunction; however, a significant difference was not observed in the stratified analysis at each stage
of cognitive dysfunction. One reason for this may be the small number of participants in this study.
There are several limitations in this study. Non-blinded, non-placebo controlled design is the main
limitation. First, the participants believed that they were taking a compound that might help them, and it
may induce a placebo effect on the MMSE-J scores. Second, the MMSE-J were administered twice at
the three-month interval. A test-retest effect on the examination could not be eliminated.
In addition, the participants of this study were regular green tea drinker. The nursing home care and
diet was not changed during study period, but baseline green tea drinking elevates the catechin
and theanine consumptions, and it might affect the changes of MMSE-J scores and atherosclerotic
Not measuring depression and other neuropsychiatric symptoms are also possible limitations.
Association between late life depression and dementia has been reported [33–36]; therefore, it is not
ruled out whether cognitive impairment is secondary to the improvement on mood. In future studies,
study designs should be improved; a blinded, placebo controlled design is adequate to evaluate the
efficacy of green tea consumption.
Our findings related to atherosclerotic risk factors showed that serum TG levels were significantly
lowered. This suggests that green tea may be protective against vascular atherosclerosis in the elderly.
The TG-lowering effect of green tea is also supported by the previously-reported meta-analysis by Zheng
et al. . However, clinical significance of the TG-lowering effects and its relationship with cognitive
function were still inconclusive, and the other atherosclerotic risk factors assessed in this study, including
LDL-C and HDL-C, did not show a significant change. The fact that the inclusion and exclusion criteria
of this study were not focused on patients with atherosclerotic risk factors, and the short term intervention
of this study are limitations; future studies on patients with atherosclerotic risk factors with long study
period should more clearly reveal both the effect of green tea consumption on these risk factors and the
relationship between the risk factors and cognitive function.
Nutrients 2014, 6 4039
In conclusion, our results suggest that green tea consumption may be effective in improving cognitive
function or reducing the progression of cognitive dysfunction in elderly individuals, and that it may
similarly reduce the progression of vascular dementia. However, there are several limitations related to
the study design. Additional long-term large-scale randomized controlled studies are needed both to
establish evidence for the effect of green tea consumption on cognitive dysfunction, and to reveal the
relationship between this effect and atherosclerotic risk factors.
We gratefully acknowledge the individuals who participated in the study and the clinical research
coordinators. We thank the medical staff at White Cross Nursing Home (Sadako Fujii, Atsuko Nakahara,
and Tsuyoshi Suzuki) for their dedicated cooperation. We also thank Philip Hawke of the University of
Shizuoka Scientific English Program for his comments on the English in the manuscript.
Kazuki Ide and Mijong Park wrote the main manuscript text, designed the study, and analyzed the
data. Hiroshi Yamada was the principal investigator as a clinical neurologist and involved in designing
the study. Norikata Takuma was a site investigator as a primary care physician and involved in designing
the study. Noriko Wakamiya supported the data management and data analysis. Junpei Nakase,
Yuuichi Ukawa and Yuko M. Sagesaka were involved in designing the study. All authors reviewed and
approved the contents of the manuscript.
Conflicts of Interest
Hiroshi Yamada was funded by a grant from the Japanese Ministry of Health, Labor and Welfare (No.
242-20-501), and a grant from ITO EN Ltd. (No. 12-311). Junpei Nakase, Yuuichi Ukawa,
Yuko M. Sagesaka are employees of ITO EN Ltd.; the company that provide the green tea powder used
in this study. Kazuki Ide, Norikata Takuma, Mijong Park, and Noriko Wakamiya declare no
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