Restricted accessResearch articleFirst published online 2025-07
Effects of Heat-Treated Green Tea Extract on Memory Function and Default Mode Network Connectivity in Individuals with Subjective Memory Impairment: A Randomized,Double-Blinded,Placebo-Controlled Trial
Given the increasing interest in the potential cognitive benefits of green tea, this study evaluated the efficacy of processed green tea products as nootropic agents. We conducted a 12-week, randomized, double-blinded, placebo-controlled trial to assess the effects of heat-treated green tea extract (HT-GTE) supplementation on memory performance in individuals with subjective memory impairment (SMI). A total of 80 participants with SMI (mean age 49.6 ± 5.6 years) were randomly assigned to either the HT-GTE group (n = 40) or the placebo group (n = 40). Memory performance was assessed using standardized composite scores at baseline and week 12. Additionally, we examined changes in functional connectivity (FC) within the default mode network (DMN), a key resting-state network associated with memory function, at both time points. Compared to the placebo group, the HT-GTE group demonstrated significant improvements in memory function after 12 weeks, as evidenced by a greater increase in composite scores (z = 2.535, P for interaction = .011). Furthermore, the HT-GTE group exhibited increased FC within the right precuneus region of the DMN (z = 2.554, P for interaction = .011). These findings underscore the potential of HT-GTE supplementation to enhance memory performance and FC within the DMN in middle-aged individuals with SMI, offering valuable insights into the cognitive benefits of green tea.
Get full access to this article
View all access options for this article.
References
1.
JessenF, WieseB, BachmannC, et al.; German Study on Aging, Cognition and Dementia in Primary Care Patients Study Group. Prediction of dementia by subjective memory impairment: Effects of severity and temporal association with cognitive impairment. Arch Gen Psychiatry, 2010; 67(4):414–422; doi: 10.1001/archgenpsychiatry.2010.30
2.
KesslerEM, BowenCE, BaerM, et al.Dementia worry: A psychological examination of an unexplored phenomenon. Eur J Ageing, 2012; 9(4):275–284; doi: 10.1007/s10433-012-0242-8
3.
ReisbergB, ShulmanMB, TorossianC, et al.Outcome over seven years of healthy adults with and without subjective cognitive impairment. Alzheimers Dement, 2010; 6(1):11–24; doi: 10.1016/j.jalz.2009.10.002
4.
TrevesTA, VerchovskyR, KlimovitzkyS, et al.Incidence of dementia in patients with subjective memory complaints. Int Psychogeriatr, 2005; 17(2):265–273; doi: 10.1017/S1041610205001596
5.
JessenF, WolfsgruberS, WieseB, et al.; German Study on Aging, Cognition and Dementia in Primary Care Patients. AD dementia risk in late MCI, in early MCI, and in subjective memory impairment. Alzheimers Dement, 2014; 10(1):76–83; doi: 10.1016/j.jalz.2012.09.017
6.
RobinsonL, TangE, TaylorJP. Dementia: Timely diagnosis and early intervention. Bmj, 2015; 350:h3029; doi: 10.1136/bmj.h3029
7.
MusialC, Kuban-JankowskaA, Gorska-PonikowskaM. Beneficial properties of green tea catechins. Int J Mol Sci, 2020; 21(5):1744; doi: 10.3390/ijms21051744
8.
ManciniE, BeglingerC, DreweJ, et al.Green tea effects on cognition, mood and human brain function: A systematic review. Phytomedicine, 2017; 34(34):26–37; doi: 10.1016/j.phymed.2017.07.008
9.
MandelSA, AmitT, WeinrebO, et al.Simultaneous manipulation of multiple brain targets by green tea catechins: A potential neuroprotective strategy for Alzheimer and Parkinson diseases. CNS Neurosci Ther, 2008; 14(4):352–365; doi: 10.1111/j.1755-5949.2008.00060.x
10.
MandelSA, AmitT, WeinrebO, et al.Understanding the broad-spectrum neuroprotective action profile of green tea polyphenols in aging and neurodegenerative diseases. J Alzheimers Dis, 2011; 25(2):187–208; doi: 10.3233/JAD-2011-101803
11.
LeeJW, LeeYK, BanJO, et al.Green tea (-)-epigallocatechin-3-gallate inhibits β-amyloid-induced cognitive dysfunction through modification of secretase activity via inhibition of ERK and NF-κB pathways in mice. J Nutr, 2009; 139(10):1987–1993; doi: 10.3945/jn.109.109785
12.
RhoT, ChoiMS, JungM, et al.Identification of fermented tea (Camellia sinensis) polyphenols and their inhibitory activities against amyloid-beta aggregation. Phytochemistry, 2019; 160:11–18; doi: 10.1016/j.phytochem.2018.12.013
13.
KimJ, FunayamaS, IzuoN, et al.Dietary supplementation of a high-temperature-processed green tea extract attenuates cognitive impairment in PS2 and Tg2576 mice. Biosci Biotechnol Biochem, 2019; 83(12):2364–2371; doi: 10.1080/09168451.2019.1659721
14.
LeeSB, ChoiEH, JeongKH, et al.Effect of catechins and high-temperature-processed green tea extract on scavenging reactive oxygen species and preventing Aβ1–42 fibrils’ formation in brain microvascular endothelium. Nutr Neurosci, 2020; 23(5):363–373; doi: 10.1080/1028415X.2018.1507618
15.
BaeHJ, KimJ, JeonSJ, et al.Green tea extract containing enhanced levels of epimerized catechins attenuates scopolamine-induced memory impairment in mice. J Ethnopharmacol, 2020; 258(258):112923; doi: 10.1016/j.jep.2020.112923
CongL, CaoC, ChengY, et al.Green tea polyphenols attenuated glutamate excitotoxicity via antioxidative and antiapoptotic pathway in the primary cultured cortical neurons. Oxid Med Cell Longev, 2016; 2016:2050435; doi: 10.1155/2016/2050435
18.
JelenkovićA, JovanovićMD, StevanovićI, et al.Influence of the green tea leaf extract on neurotoxicity of aluminium chloride in rats. Phytother Res, 2014; 28(1):82–87; doi: 10.1002/ptr.4962
19.
AbeY, UmemuraS, SugimotoKI, et al.Effect of green tea rich in γ-aminobutyric acid on blood pressure of Dahl salt-sensitive rats. Am J Hypertens, 1995; 8(1):74–79; doi: 10.1016/0895-7061(94)00141-w
20.
WangY, LiM, XuX, et al.Green tea epigallocatechin‐3‐gallate (EGCG) promotes neural progenitor cell proliferation and sonic hedgehog pathway activation during adult hippocampal neurogenesis. Mol Nutr Food Res, 2012; 56(8):1292–1303; doi: 10.1002/mnfr.201200035
21.
UnnoK, PervinM, NakagawaA, et al.Blood–brain barrier permeability of green tea catechin metabolites and their neuritogenic activity in human neuroblastoma SH‐SY5Y cells. Mol Nutr Food Res, 2017; 61(12):1700294; doi: 10.1002/mnfr.201700294
22.
AhnJW, KimS, KoS, et al.Modified (−)-gallocatechin gallate-enriched green tea extract rescues age-related cognitive deficits by restoring hippocampal synaptic plasticity. Biochem Biophys Rep, 2022; 29(29):101201; doi: 10.1016/j.bbrep.2022.101201
23.
KoS, JangWS, JeongJH, et al.(−)-Gallocatechin gallate from green tea rescues cognitive impairment through restoring hippocampal silent synapses in post-menopausal depression. Sci Rep, 2021; 11(1):910; doi: 10.1038/s41598-020-79287-x
24.
ChaJ, KimHS, KwonG, et al.Acute effects of (–)-gallocatechin gallate-rich green tea extract on the cerebral hemodynamic response of the prefrontal cortex in healthy humans. Front Neuroergon, 2023; 4:1136362; doi: 10.3389/fnrgo.2023.1136362
25.
ZhangJC, XuH, YuanY, et al.Delayed treatment with green tea polyphenol EGCG promotes neurogenesis after ischemic stroke in adult mice. Mol Neurobiol, 2017; 54(5):3652–3664; doi: 10.1007/s12035-016-9924-0
26.
ReisbergB, FerrisSH, De LeonMJ, et al.The global deterioration scale for assessment of primary degenerative dementia. Am J Psychiatry, 1982; 139(9):1136–1139; doi: 10.1176/ajp.139.9.1136
27.
TombaughTN, McIntyreNJ. The mini‐mental state examination: A comprehensive review. J Am Geriatr Soc, 1992; 40(9):922–935; doi: 10.1111/j.1532-5415.1992.tb01992.x
28.
McDermottLM, EbmeierKP. A meta-analysis of depression severity and cognitive function. J Affect Disord, 2009; 119(1–3):1–8; doi: 10.1016/j.jad.2009.04.022
29.
MoranTP. Anxiety and working memory capacity: A meta-analysis and narrative review. Psychol Bull, 2016; 142(8):831–864; doi: 10.1037/bul0000051
30.
NebesRD, BuysseDJ, HalliganEM, et al.Self-reported sleep quality predicts poor cognitive performance in healthy older adults. J Gerontol B Psychol Sci Soc Sci, 2009; 64(2):180–187; doi: 10.1093/geronb/gbn037
31.
PotterGG, HartmanM, WardT. Perceived stress and everyday memory complaints among older adult women. Anxiety Stress Coping, 2009; 22(4):475–481; doi: 10.1080/10615800802449610
32.
WilliamsJB. A structured interview guide for the Hamilton depression rating scale. Arch Gen Psychiatry, 1988; 45(8):742–747; doi: 10.1001/archpsyc.1988.01800320058007
33.
HamiltonM. Diagnosis and rating of anxiety. Br J Psychiatry, 1969; 3(special issue):76–79.
34.
BuysseDJ, ReynoldsICF, MonkTH, et al.The Pittsburgh sleep quality index: A new instrument for psychiatric practice and research. Psychiatry Res, 1989; 28(2):193–213; doi: 10.1016/0165-1781(89)90047-4
35.
CohenS. Perceived Stress in a Probability Sample of the United States. (SpacapanS, OskampS. eds.) Sage Publications Inc.: 1988; pp. 31–67.
36.
ChowHS, CaiY, AlbertsDS, et al.Phase I pharmacokinetic study of tea polyphenols following single-dose administration of epigallocatechin gallate and polyphenon E. Cancer Epidemiol Biomarkers Prev, 2001; 10(1):53–58.
37.
RobbinsTW, JamesM, OwenAM, et al.Cambridge Neuropsychological Test Automated Battery (CANTAB): A factor analytic study of a large sample of normal elderly volunteers. Dementia, 1994; 5(5):266–281; doi: 10.1159/000106735
38.
BarnettJH, BlackwellAD, SahakianBJ, et al.The paired associates learning (PAL) test: 30 years of CANTAB translational neuroscience from laboratory to bedside in dementia research. Curr Top Behav Neurosci, 2016; 28:449–474; doi: 10.1007/7854_2015_5001
39.
CacciamaniF, SalvadoriN, EusebiP, et al.Evidence of practice effect in CANTAB spatial working memory test in a cohort of patients with mild cognitive impairment. Appl Neuropsychol Adult, 2018; 25(3):237–248; doi: 10.1080/23279095.2017.1286346
40.
ÉgerháziA, BereczR, BartókE, et al.Automated Neuropsychological Test Battery (CANTAB) in mild cognitive impairment and in Alzheimer’s disease. Prog Neuropsychopharmacol Biol Psychiatry, 2007; 31(3):746–751; doi: 10.1016/j.pnpbp.2007.01.011
41.
SmallwoodJ, BernhardtBC, LeechR, et al.The default mode network in cognition: A topographical perspective. Nat Rev Neurosci, 2021; 22(8):503–513; doi: 10.1038/s41583-021-00474-4
42.
SambataroF, MurtyVP, CallicottJH, et al.Age-related alterations in default mode network: Impact on working memory performance. Neurobiol Aging, 2010; 31(5):839–852; doi: 10.1016/j.neurobiolaging.2008.05.022
43.
MevelK, ChételatG, EustacheF, et al.The default mode network in healthy aging and Alzheimer′ s disease. Int J Alzheimers Dis, 2011; 2011:535816; doi: 10.4061/2011/535816
44.
GreiciusMD, SrivastavaG, ReissAL, et al.Default-mode network activity distinguishes Alzheimer’s disease from healthy aging: Evidence from functional MRI. Proc Natl Acad Sci U S A, 2004; 101(13):4637–4642; doi: 10.1073/pnas.0308627101
45.
HutchisonRM, WomelsdorfT, AllenEA, et al.Dynamic functional connectivity: Promise, issues, and interpretations. Neuroimage, 2013; 80:360–378; doi: 10.1016/j.neuroimage.2013.05.079
46.
LairdAR, FoxPM, EickhoffSB, et al.Behavioral interpretations of intrinsic connectivity networks. J Cogn Neurosci, 2011; 23(12):4022–4037; doi: 10.1162/jocn_a_00077
47.
IdeK, MatsuokaN, YamadaH, et al.Effects of tea catechins on Alzheimer’s disease: Recent updates and perspectives. Molecules, 2018; 23(9):2357; doi: 10.3390/molecules23092357
48.
KakutaniS, WatanabeH, MurayamaN. Green tea intake and risks for dementia, alzheimer’s disease, mild cognitive impairment, and cognitive impairment: A systematic review. Nutrients, 2019; 11(5):116; doi: 10.3390/nu11051165
49.
JeongKH, ChoSY, HongYD, et al.Transport of gallocatechin gallate and catechin gallate in high-temperature-processed green tea extract from gastrointestinal tract to brain by an in vitro bio-mimic model system coupled with sequential cell cultures. J Funct Foods, 2018; 47:83–90; doi: 10.1016/j.jff.2018.05.028
50.
ColonM, NerínC. Synergistic, antagonistic and additive interactions of green tea polyphenols. Eur Food Res Technol, 2016; 242(2):211–220; doi: 10.1007/s00217-015-2532-9
51.
ShikhaD, SinghA, RangraNK, et al.Insights to therapeutic potentials, pharmaceutical formulations, chemistry and analytical methods of catechin. Phytochem Rev, 2024; 23(5):1557–1598; doi: 10.1007/s11101-024-09929-9
52.
AfzalO, DalhatMH, AltamimiAS, et al.Green tea catechins attenuate neurodegenerative diseases and cognitive deficits. Molecules, 2022; 27(21):7604; doi: 10.3390/molecules27217604
53.
SutherlandBA, RahmanRM, AppletonI. Mechanisms of action of green tea catechins, with a focus on ischemia-induced neurodegeneration. J Nutr Biochem, 2006; 17(5):291–306; doi: 10.1016/j.jnutbio.2005.10.005
54.
SebastianiG, Almeida-ToledanoL, Serra-DelgadoM, et al.Therapeutic effects of catechins in less common neurological and neurodegenerative disorders. Nutrients, 2021; 13(7):2232; doi: 10.3390/nu13072232
LangbaumJB, HendrixSB, AyutyanontN, et al.An empirically derived composite cognitive test score with improved power to track and evaluate treatments for preclinical Alzheimer’s disease. Alzheimers Dement, 2014; 10(6):666–674; doi: 10.1016/j.jalz.2014.02.002
57.
JonaitisEM, KoscikRL, ClarkLR, et al.Measuring longitudinal cognition: Individual tests versus composites. Alzheimers Dement (Amst), 2019; 11(11):74–84; doi: 10.1016/j.dadm.2018.11.006
58.
CranePK, CarleA, GibbonsLE, et al.; Alzheimer’s Disease Neuroimaging Initiative. Development and assessment of a composite score for memory in the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Brain Imaging Behav, 2012; 6(4):502–516; doi: 10.1007/s11682-012-9186-z
59.
CavannaAE, TrimbleMR. The precuneus: A review of its functional anatomy and behavioural correlates. Brain, 2006; 129(Pt 3):564–583; doi: 10.1093/brain/awl004
60.
DadarioNB, SughrueME. The functional role of the precuneus. Brain, 2023; 146(9):3598–3607; doi: 10.1093/brain/awad181
61.
FoudilSA, MacalusoE. The influence of the precuneus on the medial temporal cortex determines the subjective quality of memory during the retrieval of naturalistic episodes. Sci Rep, 2024; 14(1):7943; doi: 10.1038/s41598-024-58298-y
62.
BinnewijzendMA, SchoonheimMM, Sanz-ArigitaE, et al.Resting-state fMRI changes in Alzheimer’s disease and mild cognitive impairment. Neurobiol Aging, 2012; 33(9):2018–2028; doi: 10.1016/j.neurobiolaging.2011.07.003
63.
YokoiT, WatanabeH, YamaguchiH, et al.Involvement of the precuneus/posterior cingulate cortex is significant for the development of Alzheimer’s disease: A PET (THK5351, PiB) and resting fMRI study. Front Aging Neurosci, 2018; 10:304; doi: 10.3389/fnagi.2018.00304
64.
KochG, BonnìS, PellicciariMC, et al.Transcranial magnetic stimulation of the precuneus enhances memory and neural activity in prodromal Alzheimer’s disease. Neuroimage, 2018; 169(169):302–311; doi: 10.1016/j.neuroimage.2017.12.048
65.
SchroeterML, SteinT, MaslowskiN, et al.Neural correlates of Alzheimer’s disease and mild cognitive impairment: A systematic and quantitative meta-analysis involving 1351 patients. Neuroimage, 2009; 47(4):1196–1206; doi: 10.1016/j.neuroimage.2009.05.037
66.
MiZ, AbrahamsonEE, RyuAY, et al.Loss of precuneus dendritic spines immunopositive for spinophilin is related to cognitive impairment in early Alzheimer’s disease. Neurobiol Aging, 2017; 55:159–166; doi: 10.1016/j.neurobiolaging.2017.01.022
67.
MinersJS, PalmerJC, LoveS. Pathophysiology of hypoperfusion of the precuneus in early alzheimer’s disease. Brain Pathol, 2016; 26(4):533–541; doi: 10.1111/bpa.12331
68.
CaoW, CaoX, HouC, et al.Effects of cognitive training on resting-state functional connectivity of default mode, salience, and central executive networks. Front Aging Neurosci, 2016; 8:70; doi: 10.3389/fnagi.2016.00070
69.
UtevskyAV, SmithDV, HuettelSA. Precuneus is a functional core of the default-mode network. J Neurosci, 2014; 34(3):932–940; doi: 10.1523/JNEUROSCI.4227-13.2014
70.
Vidal-PiñeiroD, Valls-PedretC, Fernández-CabelloS, et al.Decreased default mode network connectivity correlates with age-associated structural and cognitive changes. Front Aging Neurosci, 2014; 6:256; doi: 10.3389/fnagi.2014.00256
71.
JiangR, ScheinostD, ZuoN, et al.A neuroimaging signature of cognitive aging from whole‐brain functional connectivity. Adv Sci (Weinh), 2022; 9(24):e2201621; doi: 10.1002/advs.202201621
72.
BirdCM, BurgessN. The hippocampus and memory: Insights from spatial processing. Nat Rev Neurosci, 2008; 9(3):182–194; doi: 10.1038/nrn2335
73.
FortinNJ, AgsterKL, EichenbaumHB. Critical role of the hippocampus in memory for sequences of events. Nat Neurosci, 2002; 5(5):458–462; doi: 10.1038/nn834
74.
RatnaniS, MalikS. Therapeutic properties of green tea: a review. J Multidiscip Appl Nat Sci, 2022; 2(2):90–102; doi: 10.4735/2/jmans.2774-3047.117
75.
Noguchi-ShinoharaM, YukiS, DohmotoC, et al.Consumption of green tea, but not black tea or coffee, is associated with reduced risk of cognitive decline. PLoS One, 2014; 9(5):e96013; doi: 10.1371/journal.pone.0096013
76.
CappellettiS, DariaP, SaniG, et al.Caffeine: Cognitive and physical performance enhancer or psychoactive drug? Curr Neuropharmacol, 2015; 13(1):71–88; doi: 10.2174/1570159X13666141210215655
77.
Ramírez-delaCruzM, Esteban-GarcíaP, AbiánP, et al.Effects of different doses of caffeine on cognitive performance in healthy physically active individuals. Eur J Nutr, 2024; 63(8):3025–3035; doi: 10.1007/s00394-024-03486-9
78.
ZhangB, LiuY, WangX, et al.Cognition and brain activation in response to various doses of caffeine: A near-infrared Spectroscopy Study. Front Psychol, 2020; 11:1393; doi: 10.3389/fpsyg.2020.01393
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
