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Tea for Alzheimer Prevention

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Abstract

The availability of empirical data from human studies in recent years have lend credence to the old axiomatic wisdom that health benefits of tea drinking extend to the area of cognition. Specifically, there is increasing interest as to whether tea drinking can delay or even prevent the onset of Alzheimer's disease (AD). Data from several cross-sectional studies have consistently shown that tea drinking is associated with better performance on cognitive tests. This association is supported by longitudinal data from the Singapore Longitudinal Aging Study, the Chinese Longitudinal Healthy Longevity Survey and the Cardiovascular Health Study. The only two published longitudinal analyses on clinical outcome reported conflicting results: one study reported that mid-life tea drinking was not associated with risk reduction of Alzheimer's disease in late life while the other one found that green tea consumption reduced the incidence of dementia or mild cognitive impairment. Two small trials from Korea and Japan reported encouraging but preliminary results. While the existing evidence precludes a definite conclusion as to whether tea drinking can be an effective and simple lifestyle preventive measure for AD, further research involving longer-term longitudinal studies and randomized controlled trials is clearly warranted to shed light on this topic of immense public health interest. Biological markers of tea consumption and Alzheimer diseases should be employed in future research to better delineate the underlying mechanisms of tea drinking's protective effect on cognition.
Tea for Alzheimer Prevention
L. Feng, M.-S. Chong, W.-S. Lim, T.-S. Lee, E.-H. Kua, T.-P. Ng
Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore;
the Department of Geriatric Medicine, Tan Tock Seng Hospital, Singapore; Institute of Geriatrics and Active Ageing, Tan Tock Seng Hospital, Singapore; the
Neurobehavioral Disorders Program, Duke-NUS Graduate Medical School, Singapore.
Corresponding Author: Lei Feng ( pcmfl@nus.edu.sg ), Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore (NUS) and
National University Health System (NUHS), Tel: +65 67723491 Fax: +65 67772191
J Prev Alz Dis 2015;2(2):136-141
Published online April 8, 2015, http://dx.doi.org/10.14283/jpad.2015.57
Abstract
The availability of empirical data from human studies in recent
years have lend credence to the old axiomatic wisdom that
health benefits of tea drinking extend to the area of cognition.
Specifically, there is increasing interest as to whether tea
drinking can delay or even prevent the onset of Alzheimer’s
disease (AD). Data from several cross-sectional studies have
consistently shown that tea drinking is associated with better
performance on cognitive tests. This association is supported
by longitudinal data from the Singapore Longitudinal Aging
Study, the Chinese Longitudinal Healthy Longevity Survey
and the Cardiovascular Health Study. The only two published
longitudinal analyses on clinical outcome reported conflicting
results: one study reported that mid-life tea drinking was not
associated with risk reduction of Alzheimer’s disease in late life
while the other one found that green tea consumption reduced
the incidence of dementia or mild cognitive impairment. Two
small trials from Korea and Japan reported encouraging but
preliminary results. While the existing evidence precludes
a definite conclusion as to whether tea drinking can be an
effective and simple lifestyle preventive measure for AD,
further research involving longer-term longitudinal studies
and randomized controlled trials is clearly warranted to shed
light on this topic of immense public health interest. Biological
markers of tea consumption and Alzheimer diseases should be
employed in future research to better delineate the underlying
mechanisms of tea drinking’s protective effect on cognition.
Key words: Tea, aging, Alzheimer’s disease, dementia, cognitive
decline, prevention.
Background
It was written by Lu Yu (han yu pinyin: Lù Yǔ; 733-
804) in his famous book “The Classic of Tea” that
“tea as a beverage was started by Shen Nong”. This
dated the history of tea drinking to about 5000 years ago,
when She Nong ruled China as a legendary emperor.
Today, tea is one of the most widely consumed beverages
in many countries with many well recognized health
benefits.
The effects of tea drinking on cognitive function in the
elderly and the potential of tea as a simple yet effective
lifestyle preventive measure for Alzheimer’s disease (AD)
is now attracting immense research interest. Because tea
is easily available, cheap and has no side effects at usual
levels of consumption, the potential of reducing disease
burden at the population level is considerable. There
are currently 35 millions people with AD worldwide;
since the principal risk factor of AD is age with its
incidence doubling every 5 years after 65 years of age, the
number of Alzheimer patients is expected to rise sharply
with the rapidly aging demographic trend worldwide.
Since AD is akin to a chronic condition with relatively
prolonged survival after diagnosis at the mild stage, even
a moderate reduction of incidence rate at the population
level would have a huge impact on reducing burden of
health to the healthcare system and society at large.
The urgency of establishing prevention strategy for
AD lies in the fact that none of the currently approved
drug therapies (namely cholinesterase inhibitors and
N-methyl-D-aspartate receptor antagonist) can reverse
disease progression; the condition of patients who are
taking these drugs remains stable for a year or more and
then may decline, though at a rate that is slower than that
among untreated patients (1). The search for a disease
modifying agent has proved equally elusive. Results
from recent large scale phase 3 trials involving disease
modifying agents such as the anti-amyloid-β monoclonal
antibody drugs solanezumab (2) and bapineuzumab
(3) were essentially negative. The disappointing results
from these studies have provided the impetus for the
increasing shift in attention to non-pharmacological
preventive lifestyle measures in the battle against AD.
The disease processes of AD in the brain starts at
least a decade before clinical symptoms become
apparent. It is well accepted that AD is a chronic and
complex disease and many researchers in the field
now believe that prevention may be a more promising
target than treatment of established disease. With
better understanding of contributing factors through
previous observational studies, there has been a surge
in recent years in primary prevention trials, such as the
Multi-Domain Alzheimer’s Prevention Trial (MAPT),
the Prevention of Dementia by Intensive Vascular Care
study (PreDIVA) and the Finnish Geriatric Intervention
Study to Prevent Cognitive Impairment and Disability
(FINGER). In Singapore, an early Dementia Prevention
Program (DPP) has been initiated by a group of clinicians,
136
Received February 12, 2015
Accepted for publication March 4, 2015
The Journal of Prevention of Alzheimer’s Disease - JPAD©
Volume 2, Number 2, 2015
researchers and volunteers at the Training and Research
Academy at Jurong Point (TaRA@JP) (4, 5). Since
multiple factors across the life span contribute to disease
outcomes in late life, it is premature to postulate that
targeting any single factor in isolation would significantly
reduce disease incidence, hence the rationale for the
multiple-domain approach in most of prevention studies.
Nevertheless, for scientific clarity, each of the candidate
preventive measures should be examined in isolation
with well designed observational and interventional
studies. Tea is one such promising candidates.
There is strong biological basis that supports the
assertion that tea drinking may be an effective preventive
measure for AD. Many molecular lesions have been
detected in AD, but the overarching theme that emerge
from the data is that an accumulation of misfolded
proteins in the aging brain results in oxidative and
inflammatory damage, which in turn leads to energy
failure and synaptic dysfunction (6). Tea contains various
bioactive compounds such as the catechins, theaflavins,
thearubigins and L-theanine. Those compounds may
protect the brain from AD through multiple mechanisms
including the actions on upstream events such as
amyloid formation (7, 8) and downstream events such
as oxidative stress and inflammation (9). In this paper,
we provide a brief summary of key studies that supports
the role of tea in Alzheimer prevention, along with our
recommendations for future research directions.
Tea for AD: evidence from observational
studies
Information and main findings from observational
studies are organized according to data sources. In
situations where there are multiple papers from the same
cohort, these are summarized under a single section. Key
findings from the longitudinal studies are summarized in
Table 1.
The Tsurugaya Project 1: cross-sectional
analysis (10)
The Tsurugaya Project 1 is a community-based study
among elderly Japanese living in a defined geographical
location namely the Tsurugaya district, a suburban
area of Sendai City in northern Japan. In this study,
information on the frequency of tea consumption was
collected through items in a comprehensive geriatric
assessment questionnaire. Subjects were grouped into
3 categories according to their green tea consumption
frequency: ≤3 cups/week, 4–6 cups/week or 1 cup/
day, and ≥2 cups/day; the volume of a typical cup of
green tea in Japan is 100 milliliters. Cognitive function
was assessed using the Japanese language version of
the Mini-Mental State Examination (MMSE). Cognitive
impairment was defined as MMSE total score <26. Based
on data from 1,003 subjects aged 70 years or above, the
authors reported that higher consumption of green tea
was associated with a lower prevalence of cognitive
impairment. Using < or =3 cups/week as the reference
group, the odds ratio (OR) was 0.62 (95% CI: 0.33, 1.19)
for 4-6 cups/week or 1 cup/day, and 0.46 (95% CI: 0.30,
0.72) for > or =2 cups/day.
The Hordaland Health Study: cross-sectional
analysis (11)
The Hordaland Health Study was conducted from
1997 to 1999 as a collaboration between the University
of Bergen, University of Oslo, local health services and
the Norwegian Institute of Public Health. The Cognitive
Sub-study of the project recruited and assessed 2,197
participants who were born in 1925-1927 using a
cognitive test battery that includes the Kendrick Object
Learning Test, Trail Making Test, part A (TMT-A),
modified versions of the Digit Symbol Test, Block Design,
MMSE, and Controlled Oral Word Association Test.
Information on habitual tea intake was collected using
a Food Frequency Questionnaire (FFQ). A standard cup
of tea was defined as 200 milliliters and the frequency of
consumption was given per day, week, or month. Data
from a total of 2,031 study participants aged between
70-74 years were used in the analysis on the association
between tea consumption and cognitive function. It was
found that study participants who consumed tea had
significantly better mean test scores and lower prevalence
of poor cognitive performance (defined as a score in the
highest decile for the TMT-A and in the lowest decile for
all other tests) than those who did not. The association
was dose dependent and approximately linear.
The sharpest dose-response effect of tea on cognitive
performance was up to ~200 milliliter/day.
JPAD - Volume 2, Number 2, 2015 Review Article
137
Table 1. Longitudinal studies on the association between
tea and cognitive outcome
Cohort Main ndings
SLAS Total tea consumption was signicantly associated
with a lower risk of cognitive decline
CAIDE Mid-life tea drinking was not associated with the
risk of dementia and Alzheimer’s disease in late
life.
CLHLS Tea drinkers had higher verbal uency scores
throughout the follow-up period.
CHS Tea drinking was associated with an attenuated
rate of cognitive decline in women but not in men.
Nakajima Green tea consumption was associated with
reduced incidence of overall cognitive decline
(dementia or MCI).
138
The Singapore Longitudinal Aging Study
(SLAS): cross-sectional and longitudinal
analysis
The Singapore Longitudinal Ageing Study (SLAS) is
a community-based study on health and health-related
conditions in aging. The project recruited 2,808 older
adults aged 55 and above in the southeast region of
Singapore from 2003 to 2005 and conducted regular
follow-up assessment at a time interval of approximately
2.5 years. In the SLAS cohort, global cognitive function
was assessed using a modified version of the MMSE
(12). Neuropsychological assessment was conducted
for approximately one third of the study participants
at baseline; details of the battery have been described
elsewhere (13, 14). Information on tea consumption was
collected about the habitual intake of common types of
teas among local elderly using indigenous references and
terms.
Analysis based on baseline data from 2,501 SLAS
participants showed an inverse relationship between
tea consumption and the odds of having cognitive
impairment defined as a MMSE total score of less than
24 (15). Compared with the reference group of rare or
no tea intake, the ORs for low, medium, and high levels
of tea intake were 0.56, 0.45, and 0.37 respectively (P
for linear trend < 0.001). The protective effects were
most evident for black (fermented) and oolong (semi-
fermented) teas, the predominant types consumed by
this population. Analysis based on data from 716 SLAS
subjects who had neuropsychological test data showed
that tea consumption was independently associated
with better performances on global cognition (B=0.055,
P=0.03), memory (B=0.031, P=0.01), executive function
(B=0.032, P=0.009), and information processing speed
(B=0.04, P=0.001) (16). Both black/oolong tea and green
tea consumption were associated with better cognitive
performance. Analysis based on 1,438 SLAS subjects
who had complete MMSE data at baseline and repeated
MMSE at follow-up revealed reverse association between
tea drinking and the odds of having cognitive decline
defined as a MMSE total score drop of 1 point or greater
during the follow-up period (15). Compared with the
OR for rare or no tea intake, the ORs for low, medium,
and high levels of tea intake were 0.74, 0.78, and 0.57
respectively (P for linear trend = 0.042).
The Chinese Longitudinal Healthy Longevity
Survey (CLHLS): longitudinal analysis and
gene-environment (G×E) interaction
The CLHLS is a population based cohort study of
oldest-old and comparative sub-sample of younger elders
in China. In the CLHLS cohort, cognitive function was
measured by the verbal fluency test at baseline (n=7,139),
year 2000 (n=4,081), year 2002 (n=2,288) and year 2005
(n=913) for oldest-old participants (80-115 years old) (17).
Self-reported information on tea consumption habits at
the age of 60 and year 1999 was collected through face-to-
face interviews. The frequency was recorded as “almost
every day” or “occasionally” or “rarely or never”. In the
linear mixed effects model that adjusted for age, gender,
years of schooling, physical exercise and activities score,
the regression coefficient for daily drinking (at age
60) and occasional drinking was 0.72 (P<0.0001) and
0.41(P=0.01) respectively. Tea drinkers had higher verbal
fluency scores throughout the follow-up period . Similar
results were found for current tea drinking status at the
study baseline year (1998) as a predictor variable.
An interesting GxE interactions between FOXO
genotypes and tea drinking was revealed in cross-
sectional analysis that involved 822 CLHLS participants
who were aged 92 and above (18). Associations between
tea drinking and reduced cognitive disability defined
using MMSE cutoffs were much stronger among
carriers of the genotypes of FOXO1A-266 or FOXO3-310
or FOXO3-292 compared with noncarriers, and it was
reconfirmed by analysis of three-way interactions across
FOXO genotypes, tea drinking at around age 60, and at
present time.
The Cardiovascular Health Study (CHS):
longitudinal analysis
The CHS is a prospective longitudinal study of
cardiovascular disease in participants aged 65 years
and older. In this study, 5,201 men and women were
enrolled in 1989 and 1990 from a random sample of
Medicare-eligible residents in four U.S. communities
(19). In the CHS, cognitive performance was assessed
using the Modified Mini-Mental State (3MS) examination
which was administered annually up to 9 times. The
relationship of tea consumption on changes in cognitive
function was analyzed for 4,809 CHS participants using
Linear Mixed Models. The authors reported modestly
Review Article TEA FOR ALZHEIMER PREVENTION
Table 2. Interventional studies on tea and cognitive outcome
Country, City Study design Sample size Main nding
Korea, Daejeon RCT 91 Green tea extract and L-theanine led to improvements in memory
but the changes were not signicant at an alpha level of 0.05.
Japan, Higashi-Murayama Single-arm trial 12 Green tea improved cognitive function in a group of Japanese
elderly with diagnosis of Alzheimer disease, Vascular dementia or
Dementia with Lewy bodies.
JPAD - Volume 2, Number 2, 2015
139
Review Article
reduced rates of cognitive decline for levels of tea
consumption among women, with no such effect for men.
The adjusted mean rate of decline for the reference group
(women who drank less than 5 cups of tea per year) was
1.30 standard 3MS points per year. Compared with the
reference group, female participants drinking tea 5-10
times/year, 1-3 times/month, 1-4 times/week, and 5+
times/ week had average annual rates of decline (95%
CI) of 3MSE scores that were 0.23 (-0.14-0.60), 0.44 (0.13-
0.75), 0.53 (0.24-0.82), and 0.29 (0.01-0.57) points lower,
respectively.
The Cardiovascular risk factors, Aging and
Dementia (CAIDE) study: longitudinal analysis
The CAIDE study is the first study that examined
the association between midlife tea consumption and
dementia status in late life. The investigators selected
a random sample from survivors of population-based
random samples rstly studied within the North Karelia
Project and the FINMONICA study in 1972, 1977, 1982
or 1987 and completed follow-up assessments in 1998
for 1,409 individuals who were living in the study area
in Eastern Finland (in Joensuu or Kuopio) (20). A total of
61 person were identified as demented, out of which 48
had AD. Midlife tea consumption status of CAIDE study
subjects was dichotomized into those not drinking tea (0
cup/day) versus those drinking tea (at least 1 cup/day).
In the logistic regression model, the OR of dementia and
AD for tea drinkers was 1.04 (95% CI 0.59–1.84) and 0.91
(95% CI 0.48–1.71) respectively. There was no association
between midlife tea consumption and the risk of AD in
late life.
The Nakajima Project: longitudinal analysis
(21)
The Nakajima Project is the first longitudinal study
that examined the association between green tea and the
incidence of dementia and MCI. It is a population-based
cohort study that examined the correlations between
lifestyle factors and dementia in elderly Japanese. The
study was conducted in Nakajima, in the Nanao district
of Ishikawa Prefecture, Japan. Among 490 Nakajima
Project participants who were assessed as cognitively
normal in 2007-2008 (baseline); 26 incident dementia
cases and 64 mild cognitive impairment (MCI) cases were
ascertained at the follow-up survey in 2011-2013. The OR
for combined incidence of dementia and MCI was 0.32
for daily green tea consumers and 0.47 for participants
who consumed green tea 1-6 days per week compared
with participants who did not consume green tea at
baseline. There was no association between black tea
and the incidence of dementia and MCI but the number
of black tea consumers was very small: only 86 (17.6%)
of the participants consumed black tea at least 1 day per
week, and the number of daily tea consumers was only 6
(in contrast, the number of daily green tea consumer was
157).
Tea for AD: evidence from interventional
studies
Two interventional studies exist in the literature,
one from Korea and the other from Japan. The studies
targeted individuals who had self-reported cognitive
deficits or were previously diagnosed with dementia,
and hence strictly speaking, should not be considered
as primary prevention trials. Nevertheless, the results
from those two trials provide important insights from
the preliminary evidence and are hence included in this
discussion.
The Daejeon University Oriental Hospital
study: Randomized Controlled Trial (22)
This is a randomized, double-blind, placebo-controlled
study that tests the potential of LGNC-07, a nutraceutical
ingredient containing green tea extract (GTE) and
L-theanine, as an intervention for cognitive improvement
among individual with subjective cognitive impairment.
The investigators recruited ninety-one participants (25
men and 66 women, MMSE total scores ranging from
21 to 26) from Daejeon University Oriental Hospital and
randomly allocated them into LGNC-07 treatment or
placebo arms. Participants took two 430-mg capsules of
treatment or placebo twice a day 30 minutes after meals
for 16 weeks. Treatment capsules contained 360 mg of
GTE, 60 mg of L-theanine, 5.7 mg of silicone dioxide,
and 4.3 mg of magnesium stearate. Neuropsychological
tests and electroencephalography were conducted to
evaluate the effect of LGNC-07 on memory and attention.
Electroencephalograms were recorded in 24 randomly
selected subjects hourly for 3 hours in eye-open, eye-
closed, and reading states after a single dose (LGNC-07,
n = 12; placebo, n = 12).
The investigators reported that LGNC-07 led to
improvement in memory by marginally increasing
delayed recognition in the Rey-Kim memory test
(P = 0.057). Stratified analyses showed that LGNC-07
improved memory and selective attention by significantly
increasing the Rey-Kim memory quotient and word
reading in the subjects with MMSE (Korean version)
scores of 21-23 (LGNC-07, n = 11; placebo, n = 9). Brain
theta waves, an indicator of cognitive alertness, were
increased significantly in the temporal, frontal, parietal,
and occipital areas after 3 hours in the eye-open and
reading states.
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Review Article
The White Cross Nursing Home study: single
arm trial
This is a small study that was conducted from July
to September 2012 at the White Cross Nursing Home in
Higashi-Murayama, Japan. Study participants were asked
to consume green tea powder (2 grams /day, containing
227 milligrams catechins and 42 milligrams theanine)
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. Participants were advised to maintain
their customary intake of home-brewed green tea or tea
beverages during the study period.
Analysis based on twelve participants (2 men, 10
women; 3 AD, 8 Vascular Dementia, 1 Dementia with
Lewy bodies; mean age 88 years) who had complete data
for the trial showed significant improvement in MMSE
(Japanese version): the mean score improved from 15.3
± 7.7 before intervention to 17.0 ± 8.2 (P = 0.03). The
study demonstrates that green tea improves cognitive
function even at relatively low catechin and theanine
concentrations which can be obtained from ordinary
levels of daily green tea intake. It should be noted that the
concentration of bioactive compounds in the daily dose of
green tea powder employed in this study approximately
equates to two to four cups of bottled or home-brewed
green tea.
Conclusions and recommendations
Take together, the body of evidence as summarized
above appears to support the role of tea as an effective
yet simple lifestyle preventive measure for AD. Future
research involving more robust study designs are
warranted, especially longitudinal studies that examine
clinical outcomes and interventional studies that target
individuals at high risk of developing AD. Given that tea
drinking is relatively safe and have many concomitant
health benefits, practitioners can generally recommend
tea drinking as a simple lifestyle measure for overall
cognitive health and possible benefit in AD prevention,
especially in populations with an established tea-drinking
culture. As for types of tea, current observational data
do not support the superiority of any type of tea (such as
green tea) over others (such as black tea).
It should be noted that although the neuroprotective
role of tea consumption is biologically plausible, there
is a lack of good data on underlying neural mechanisms
from human studies. Recently, Schmidt and colleagues
demonstrated that green tea extract enhanced parieto-
frontal connectivity during working memory, and that
the magnitude of increased connectivity was positively
correlated with improvement in task performance (23). It
is unknown whether long-term tea consumption would
induce functional and structural changes in the brain.
We therefore recommend that future studies should
include biomarkers of Alzheimer pathophysiology such
as structural and functional imaging modalities involving
Magnetic Resonance Imaging (MRI) and Positron
Emission Tomography (PET), as well as cerebrospinal
fluid based biomarkers involving tau and amyloid.
Biomarkers of tea intake such as catechin and theanine
(24, 25) should also be monitored.
Lastly, we recommend that a large prevention trial that
is adequately powered akin to the Ginkgo Evaluation of
Memory (GEM) study (26, 27) be conducted to examine
the preventative effect of tea drinking among subjects
with normal cognition at baseline. The authors look
forward to data from such a trial to confirm or reject the
notion of tea in the prevention of Alzheimer’s disease.
Dr Feng received conference travel support from Amore Pacific, Republic of Korea.
He is currently planning grant application on the role of tea as a preventive for dementia.
Conflict of interests: None of the co-authors reported potential conflict of
interests.
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... While the existing evidence precludes a definite conclusion as to whether tea drinking can be preventive from AD, further research including longer-term longitudinal studies and randomized controlled trials (RCT) is warranted to shed light on this topic. Biological markers of tea consumption and AD should be employed in future research to better delineate the underlying mechanisms of tea's benefits on cognition [18]. ...
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Many observational and clinical studies have shown that consumption of diets rich in plant polyphenols have beneficial effects on various diseases such as cancer, obesity, diabetes, cardiovascular diseases, and neurodegenerative diseases (NDDs). Animal and cellular studies have indicated that these polyphenolic compounds contribute to such effects. The representative polyphenols are epigallocatechin-3-O-gallate in tea, chlorogenic acids in coffee, resveratrol in wine, and curcumin in curry. The results of human studies have suggested the beneficial effects of consumption of these foods on NDDs including Alzheimer's and Parkinson's diseases, and cellular animal experiments have provided molecular basis to indicate contribution of these representative polyphenols to these effects. This article provides updated information on the effects of these foods and their polyphenols on NDDs with discussions on mechanistic aspects of their actions mainly based on the findings derived from basic experiments.
... Although individual constituents of tea have been related to the roles of maintaining cognitive abilities and preventing cognitive decline, a study with behavioural and neurophysiological measures showed that there was a degraded effect or no effect when a constituent was administered alone and a significant effect was observed only when constituents were combined [20]. The superior effect of the constituent combination was also demonstrated in a comparative experiment [21] that suggested that tea itself should be administered instead of tea extracts; a review of tea effects on the prevention of Alzheimer's disease (AD) [22], found that the neuroprotective role of herbal tea was apparent in eight out of nine studies. ...
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The majority of tea studies have relied on neuropsychological measures, and much fewer on neuroimaging measures, especially for interregional connections. To date, there has been no exploration of the effect of tea on system-level brain networks. We recruited healthy older participants to two groups according to their history of tea drinking frequency and investigated both functional and structural networks to reveal the role of tea drinking on brain organization. The results showed that tea drinking gave rise to the more efficient structural organization, but had no significant beneficial effect on the global functional organization. The suppression of hemispheric asymmetry in the structural connectivity network was observed as a result of tea drinking. We did not observe any significant effects of tea drinking on the hemispheric asymmetry of the functional connectivity network. In addition, functional connectivity strength within the default mode network (DMN) was greater for the tea-drinking group, and coexistence of increasing and decreasing connective strengths was observed in the structural connectivity of the DMN. Our study offers the first evidence of the positive contribution of tea drinking to brain structure and suggests a protective effect on age-related decline in brain organisation.
... The addition of tea biomarkers may help to reduce measurement errors and also provide clues on what are the compounds that contribute to observed cognitive benefits, if any. Biomarkers of brain pathology such as Magnetic Resonance Imaging (MRI), Positron Emission Tomography (PET) and cerebrospinal fluid based biomarkers of tau and amyloid can be monitored [20] because such biomarkers are more sensitive than cognitive tests in detecting smaller effects. ...
Article
Background: Accumulating evidence supports the neuroprotective effects of bioactive compounds from tea leaves. There are limited data from black tea consumption populations. Objective: To determine whether black tea consumption is associated with cognitive decline among older men. Methods: We chose to study the association between black tea consumption and cognition using data from the Osteoporotic Fractures in Men (MrOS) cohort, which collected information on tea consumption at baseline and has repeatedly assessed cognitive function in 3,844 men aged 65+ years (mean = 72.4 years). We defined tea drinkers as those who drank black tea at least once per week and further grouped them into weekly drinkers and daily drinkers. Cognitive function was assessed at baseline and approximately 7 years later using the Modified Mini-Mental State Examination (3MSE). Multivariable logistic regression and linear regression models were constructed to assess the association between black tea consumption and risk of fast cognitive decline as a binary variable and change in 3MSE scores as continuous variable. Fast cognitive decline was defined as decline in 3MSE >1.5 standard deviation of mean change score. Models were adjusted for age, education level, and baseline cognitive scores. Results: Weekly and daily black tea drinkers were 24.8% and 12.4% of the study cohort, respectively. Fast cognitive decline occurred in 243 (6.3%) participants. Tea consumption was not associated with risk of cognitive decline, nor was tea associated with cognitive decline measured by absolute change in 3MSE scores. Conclusions: There was no association of black tea consumption and cognitive decline among older men in the US.
... Data from several cross-sectional studies consistently showed that tea drinking is associated with better performance on cognitive tests. Tea consumption is considered to be one simple lifestyle adjustment that may either prevent or treat the cognitive declines associated with neurodegenerative AD [10,11]. ...
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Neurodegenerative disease Alzheimer’s disease (AD) is attracting growing concern because of an increasing patient population among the elderly. Tea consumption is considered a natural complementary therapy for neurodegenerative diseases. In this paper, epidemiological studies on the association between tea consumption and the reduced risk of AD are reviewed and the anti-amyloid effects of related bioactivities in tea are summarized. Future challenges regarding the role of tea in preventing AD are also discussed.
... Epigallocatechin gallate inhibited β-amyloid formation involved in Alzheimer's disease, modulated amyloid precursor protein cleavage, and reduced cerebral amyloidosis in mice [72]. A cross-sectional study has revealed that green tea consumption significantly reduced the risk of cognitive dysfunction [73], and was beneficial in Alzheimer's disease [74][75][76][77]. Moreover, the long-term consumption of tea had an inverse correlation with the onset of Parkinson's disease in a population study [58,78]. ...
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Catechins are polyphenolic compounds—flavanols of the flavonoid family found in a variety of plants. Green tea, wine and cocoa-based products are the main dietary sources of these flavanols. Catechins have potent antioxidant properties, although in some cases they may act in the cell as pro-oxidants. Catechins are reactive oxygen species (ROS) scavengers and metal ion chelators, whereas their indirect antioxidant activities comprise induction of antioxidant enzymes, inhibition of pro-oxidant enzymes, and production of the phase II detoxification enzymes and antioxidant enzymes. Oxidative stress and ROS are implicated in aging and related dysfunctions, such as neurodegenerative disease, cancer, cardiovascular diseases, and diabetes. Due to their antioxidant properties, catechins may be beneficial in preventing and protecting against diseases caused by oxidative stress. This article reviews the biochemical properties of catechins, their antioxidant activity, and the mechanisms of action involved in the prevention of oxidative stress-caused diseases.
Chapter
Plant-derived polyphenols catechins (flavan-3-ols) are the main chemical constituents of green tea and cocoa beans. Furthermore, they are found in lesser amounts in many fruits, vegetables, and their products. In numerous studies, catechins have been demonstrated to scavenge free oxygen radicals, to enhance cellular antioxidant defense, and to suppress inflammation processes. Oxidative stress, neuroinflammation, insufficient neurotrophic factor support, and mitochondrial dysfunction have been implicated in cognitive decline and progression of neurodegenerative diseases. This chapter reviews the chemical properties of catechins, their role in inflammation, neuroprotection, and modulation of brain mitochondria.
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n January 2018, the investigators from Eli Lily’s EXPEDITION3 trial published their negative findings of a large phase 3 trial on the antibody Solanezumab (1). The lacking of statistically significant between-group difference on primary endpoint dampened enthusiasm again, and added the study to a long and growing list of failed trials (including EXPEDITION 1 and EXPEDITION2 from the same company) in the field of AD therapeutics. Without promising disease modifying agents, more and more clinicians and scientists in the field start to believe that prevention is better (and maybe easier) than treatment. In the West, scientists, lobbyists and advocacy groups are working hard in persuading the governments and funding agencies to invest more on efforts related to primary prevention of AD. A major study, the US POINTER will soon be initiated in 2018 in the U.S.
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Responses: We thank Dr Joob and Dr Wiwanitkit for their interest in our research work and the valuable comments and suggestions they have provided. I fully agree with them that some uncontrolled factors, such as the intake of other foods, beverages or activities, may help protect against depressive and anxiety symptoms, and hence residual confounding cannot be completely ruled out. Further investigation is needed for a definitive conclusion. Indeed, motivated by growing evidence on neuroprotective benefits of tea consumption (1), my coworkers and I are now planning a new study in which we aim to assess the effects of tea drinking on brain health in a randomized controlled trial.
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To the editor, the publication on “Associations of Long-Term Tea Consumption with Depressive and Anxiety Symptoms in Community-Living Elderly” is very interesting (1). Chan et al. concluded that “There was evidence suggesting that long-term tea consumption was associated with reduced depressive and anxiety symptoms among community-living elderly (1).” In fact, tea drinking is a rooted behavior among Chinese Asian population. The health usefulness of tea is approved. Neuroprotective system due to tea drinking is believed to due to the active ingredients including to flavonoids (2). In a recent report, the green tea was found to have more neuroprotective activity than red and black tea (3). It is no doubt that the long-term tea consumption can result in neuroprotective effect as reported by Chan et al (1). However, as noted by Chan, further investigation is needed. The main concern for the present report is confounding effect that is not controllable. The studied elderly might have other foods, beverages or activities that can help protect against depressive and anxiety symptoms. Finally, tea contain caffeine, an extremely high dose drinking might result in problem, induction of anxiety instead of prevention of anxiety (4).
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Logistic regression analysis based on data from 822 Han Chinese oldest old aged 92+ demonstrated that interactions between carrying FOXO1A-266 or FOXO3-310 or FOXO3-292 and tea drinking at around age 60 or at present time were significantly associated with lower risk of cognitive disability at advanced ages. Associations between tea drinking and reduced cognitive disability were much stronger among carriers of the genotypes of FOXO1A-266 or FOXO3-310 or FOXO3-292 compared with noncarriers, and it was reconfirmed by analysis of three-way interactions across FOXO genotypes, tea drinking at around age 60, and at present time. Based on prior findings from animal and human cell models, we postulate that intake of tea compounds may activate FOXO gene expression, which in turn may positively affect cognitive function in the oldest old population. Our empirical findings imply that the health benefits of particular nutritional interventions, including tea drinking, may, in part, depend upon individual genetic profiles.
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Our objective was to determine whether the consumption of green tea, coffee, or black tea influences the incidence of dementia and mild cognitive impairment (MCI) in older people. We conducted a population-based prospective study with Japanese residents aged >60 years from Nakajima, Japan (the Nakajima Project). Participants received an evaluation of cognitive function and blood tests. The consumption of green tea, coffee, and black tea was also evaluated at baseline. Of 723 participants with normal cognitive function at a baseline survey (2007-2008), 490 completed the follow up survey in 2011-2013. The incidence of dementia during the follow-up period (mean ± SD: 4.9±0.9 years) was 5.3%, and that of MCI was 13.1%. The multiple-adjusted odds ratio for the incidence of overall cognitive decline (dementia or MCI) was 0.32 (95% CI: 0.16-0.64) among individuals who consumed green tea every day and 0.47 (95% CI: 0.25-0.86) among those who consumed green tea 1-6 days per week compared with individuals who did not consume green tea at all. The multiple-adjusted odds ratio for the incidence of dementia was 0.26 (95% CI: 0.06-1.06) among individuals who consumed green tea every day compared with those who did not consume green tea at all. No association was found between coffee or black tea consumption and the incidence of dementia or MCI. Our results indicate that green tea consumption is significantly associated with reduced risk of cognitive decline, even after adjustment for possible confounding factors.
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Alzheimer's disease is characterized by amyloid-beta plaques, neurofibrillary tangles, gliosis, and neuronal loss. Solanezumab, a humanized monoclonal antibody, preferentially binds soluble forms of amyloid and in preclinical studies promoted its clearance from the brain. In two phase 3, double-blind trials (EXPEDITION 1 and EXPEDITION 2), we randomly assigned 1012 and 1040 patients, respectively, with mild-to-moderate Alzheimer's disease to receive placebo or solanezumab (administered intravenously at a dose of 400 mg) every 4 weeks for 18 months. The primary outcomes were the changes from baseline to week 80 in scores on the 11-item cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog11; range, 0 to 70, with higher scores indicating greater cognitive impairment) and the Alzheimer's Disease Cooperative Study-Activities of Daily Living scale (ADCS-ADL; range, 0 to 78, with lower scores indicating worse functioning). After analysis of data from EXPEDITION 1, the primary outcome for EXPEDITION 2 was revised to the change in scores on the 14-item cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog14; range, 0 to 90, with higher scores indicating greater impairment), in patients with mild Alzheimer's disease. Neither study showed significant improvement in the primary outcomes. The modeled difference between groups (solanezumab group minus placebo group) in the change from baseline was -0.8 points for the ADAS-cog11 score (95% confidence interval [CI], -2.1 to 0.5; P=0.24) and -0.4 points for the ADCS-ADL score (95% CI, -2.3 to 1.4; P=0.64) in EXPEDITION 1 and -1.3 points (95% CI, -2.5 to 0.3; P=0.06) and 1.6 points (95% CI, -0.2 to 3.3; P=0.08), respectively, in EXPEDITION 2. Between-group differences in the changes in the ADAS-cog14 score were -1.7 points in patients with mild Alzheimer's disease (95% CI, -3.5 to 0.1; P=0.06) and -1.5 in patients with moderate Alzheimer's disease (95% CI, -4.1 to 1.1; P=0.26). In the combined safety data set, the incidence of amyloid-related imaging abnormalities with edema or hemorrhage was 0.9% with solanezumab and 0.4% with placebo for edema (P=0.27) and 4.9% and 5.6%, respectively, for hemorrhage (P=0.49). Solanezumab, a humanized monoclonal antibody that binds amyloid, failed to improve cognition or functional ability. (Funded by Eli Lilly; EXPEDITION 1 and 2 ClinicalTrials.gov numbers, NCT00905372 and NCT00904683.).
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It has been proposed that green tea extract may have a beneficial impact on cognitive functioning, suggesting promising clinical implications. However, the neural mechanisms underlying this putative cognitive enhancing effect of green tea extract still remain unknown. This study investigates whether the intake of green tea extract modulates effective brain connectivity during working memory processing and whether connectivity parameters are related to task performance. Using a double-blind, counterbalanced, within-subject design, 12 healthy volunteers received a milk whey-based soft drink containing 27.5 g of green tea extract or a milk whey-based soft drink without green tea as control substance while undergoing functional magnetic resonance imaging. Working memory effect on effective connectivity between frontal and parietal brain regions was evaluated using dynamic causal modeling. Green tea extract increased the working memory induced modulation of connectivity from the right superior parietal lobule to the middle frontal gyrus. Notably, the magnitude of green tea induced increase in parieto-frontal connectivity positively correlated with improvement in task performance. Our findings provide first evidence for the putative beneficial effect of green tea on cognitive functioning, in particular, on working memory processing at the neural system level by suggesting changes in short-term plasticity of parieto-frontal brain connections. Modeling effective connectivity among frontal and parietal brain regions during working memory processing might help to assess the efficacy of green tea for the treatment of cognitive impairments in psychiatric disorders such as dementia.
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Bapineuzumab, a humanized anti-amyloid-beta monoclonal antibody, is in clinical development for the treatment of Alzheimer's disease. We conducted two double-blind, randomized, placebo-controlled, phase 3 trials involving patients with mild-to-moderate Alzheimer's disease--one involving 1121 carriers of the apolipoprotein E (APOE) ε4 allele and the other involving 1331 noncarriers. Bapineuzumab or placebo, with doses varying by study, was administered by intravenous infusion every 13 weeks for 78 weeks. The primary outcome measures were scores on the 11-item cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog11, with scores ranging from 0 to 70 and higher scores indicating greater impairment) and the Disability Assessment for Dementia (DAD, with scores ranging from 0 to 100 and higher scores indicating less impairment). A total of 1090 carriers and 1114 noncarriers were included in the efficacy analysis. Secondary outcome measures included findings on positron-emission tomographic amyloid imaging with the use of Pittsburgh compound B (PIB-PET) and cerebrospinal fluid phosphorylated tau (phospho-tau) concentrations. There were no significant between-group differences in the primary outcomes. At week 78, the between-group differences in the change from baseline in the ADAS-cog11 and DAD scores (bapineuzumab group minus placebo group) were -0.2 (P=0.80) and -1.2 (P=0.34), respectively, in the carrier study; the corresponding differences in the noncarrier study were -0.3 (P=0.64) and 2.8 (P=0.07) with the 0.5-mg-per-kilogram dose of bapineuzumab and 0.4 (P=0.62) and 0.9 (P=0.55) with the 1.0-mg-per-kilogram dose. The major safety finding was amyloid-related imaging abnormalities with edema among patients receiving bapineuzumab, which increased with bapineuzumab dose and APOE ε4 allele number and which led to discontinuation of the 2.0-mg-per-kilogram dose. Between-group differences were observed with respect to PIB-PET and cerebrospinal fluid phospho-tau concentrations in APOE ε4 allele carriers but not in noncarriers. Bapineuzumab did not improve clinical outcomes in patients with Alzheimer's disease, despite treatment differences in biomarkers observed in APOE ε4 carriers. (Funded by Janssen Alzheimer Immunotherapy and Pfizer; Bapineuzumab 301 and 302 ClinicalTrials.gov numbers, NCT00575055 and NCT00574132, and EudraCT number, 2009-012748-17.).
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Objective: We examined the longitudinal association between tea drinking frequency and cognitive function in a large sample of oldest-old Chinese. Design: population-based longitudinal cohort study. Setting: The Chinese Longitudinal Healthy Longevity Survey (CLHLS). Participants: 7139 participants aged 80 to 115 (mean age 91.4 years) who provided complete data at baseline (year 1998). Measurements: Current frequency of tea drinking and past frequency at age 60 were ascertained at baseline, and baseline and follow-up cognitive assessments were performed in the years 1998 (n=7139), 2000 (n=4081), 2002 (n=2288) and 2005 (n=913) respectively. Verbal fluency test was used as measure of cognitive function. Results: Tea drinking was associated at baseline with higher mean (SD) verbal fluency scores: daily=10.7 (6.6), occasional=9.2 (5.8), non-drinker=9.0 (5.5). In linear mixed effects model that adjusted for age, gender, years of schooling, physical exercise and activities score, the regression coefficient for daily drinking (at age 60) and occasional drinking was 0.72 (P<0.0001) and 0.41(P=0.01) respectively. Tea drinkers had higher verbal fluency scores throughout the follow-up period but concurrently had a steeper slope of cognitive decline as compared with non-drinkers (coefficient for the interaction term Time*Daily drinking= -0.12, P=0.02; "Time" was defined as the time interval from baseline to follow-up assessments in years). Similar results were found for current tea drinking status at study baseline year (1998) as predictor variable. Conclusion: Regular tea drinking is associated with better cognitive function in oldest-old Chinese.
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l-Theanine, an amino acid in green tea, is suggested to improve cognition and mood. Therefore, l-theanine is available as a supplement and is now used as an ingredient in functional drinks. Because data on the metabolic fate of l-theanine from human studies are lacking, we investigated the kinetics of l-theanine uptake and its metabolites, ethylamine and glutamic acid, in healthy participants. Within a randomized crossover study, 12 participants ingested a bolus of 100 mg l-theanine via capsules or green tea. On further occasions, 3 participants received 50 and 200 mg l-theanine via capsules. Blood and urine were collected before and up to 24 h postconsumption to determine the concentrations of l-theanine, proteinogenic amino acids, and ethylamine in plasma, erythrocytes, and urine by HPLC. l-Theanine increased in plasma, erythrocytes, and urine with comparable results after both treatments. The maximum plasma concentration of l-theanine occurred 0.8 h after intake of 100 mg l-theanine via capsules (24.3 ± 5.7 μmol/L) and tea (26.5 ± 5.2 μmol/L), respectively. The AUC of l-theanine in plasma increased dose dependently after intake of 50, 100, and 200 mg l-theanine via capsules. Moreover, ethylamine and glutamic acid increased in plasma and were excreted by urine after intake of capsules and tea. In conclusion, l-theanine is rapidly absorbed and seems to be hydrolyzed to ethylamine and glutamic acid. A minor part of l-theanine is retained in erythrocytes. Kinetics and urinary excretion of l-theanine, ethylamine, and glutamic acid are comparable after both treatments. Thus, functional effects of l-theanine intake may result from l-theanine, ethylamine, or glutamic acid.
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This study aimed to determine the stratified normative data by age and education for a modified version of the Mini-Mental State Examination (MMSE) test from a large sample of community-dwelling Chinese older adults in Singapore, and to examine the MMSE's value in detecting early cognitive impairment. We studied 1,763 Chinese older adults with normal cognitive function and 121 Chinese older adults with early cognitive impairment (Clinical Dementia Rating global score 0.5). Normative MMSE values were derived for each of the 15 strata classified by age (three groups) and education level (five groups). Receiver operating characteristic curve analysis was conducted for the whole sample and each of the three education subgroups (no education, primary, secondary and above). Education level and age significantly influenced the normative values of MMSE total scores in Chinese older adults with normal cognitive function. For the purpose of detecting early cognitive impairment, an optimal balance between sensitivity (Se) and specificity (Sp) was obtained at a cutoff score of 25, 27 and 29 for each of the three education groups, respectively. For the whole sample, the optimal cutoff point was 26 (Se 0.61, Sp 0.84, area under curve 0.78). Age and education level must be taken into account in the interpretation of optimal cutoffs for the MMSE. Although widely used, the MMSE has limited value in detecting early cognitive impairment; tests with better performance should be considered in clinical practice.
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This review summarizes the literature on the prevalence and incidence rates of dementia in Chinese populations, including survey results outside mainland China. We identified 15 prevalence studies and five incidence studies. The studies consistently reported sharply increased prevalence and incidence rates of dementia with increasing age. As estimated, there are at least 6,464,040 dementia patients in mainland China alone and we expect the number to rise in the coming decades. It is clear that dementia will be a new epidemic of the 21st century without major public health policies and preventive measures that target at the disease. We urge more research and hope that we will be able to prevent dementia or at least delay the onset in the near future with evidence-based measures.