Prevention of Cognitive Decline in ApoE4 Carriers With Subjective Cognitive Decline After EGCG and a Multimodal Intervention

NCT ID: NCT03978052

Last Updated: 2024-03-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 129 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-10-30
• Study Completion Date: 2023-06-28

Brief Summary

Alzheimer's disease (AD) neuropathology is characterized by deposits of insoluble amyloid β-peptide (Aβ) in extracellular plaques and aggregated tau protein, which is found largely in the intracellular neurofibrillary tangles. Current knowledge, has allowed a shift in the definition of AD from a syndromal to a biological construct, based on biomarkers that are proxies of pathology. However, little is known about mechanisms underlying the disease progression at its early stages. The loss of dendritic spines, the primary locus of excitatory synaptic transmission in the mammalian central nervous may be linked to cognitive and memory impairment in AD: A multimodal lifestyle change intervention (dietary, physical activity and cognition) combined with epigallocatechin gallate (EGCG) will slow down cognitive decline and improve brain connectivity in a population of participants with subjective cognitive decline (SCD). In humans, alterations in functional connectivity (FC) have been observed in early AD stages, subjective cognitive decline (SCD) and mild cognitive impairment (MCI). A hyper-synchronized anterior network and a posterior network characterized by a decrease in FC are the spatial features. These disruptions also seen in AD indicate that FC alterations appear very early in the course of the disease . Experimental research strongly suggests that in order to increase our cerebral reserves, we have to follow a lifestyle that takes into account many factors. Clinical studies provided evidence that individuals with more cerebral reserves are those who have a high level of education, who maintain regular physical activity and who eat in a healthy way. The environmental enrichment (EE) animal models confirmed that the experience plays a key role in increasing brain plasticity phenomena .There is a growing understanding that a valid therapeutic emerging approach in AD is prevention. A large number of modifiable risk factors for AD have been identified in observational studies, many of which do not appear to exert effects through amyloid or tau. This suggests that primary prevention studies focusing on risk reduction and lifestyle modification may offer additional benefits. The therapeutic approach proposed in the present project aims at improving synaptic plasticity and functional connectivity in early stages of AD, and specifically in SCD in the context of a personalized medicine approach that includes a multimodal intervention (nutritional, physical, cognitive and medical) looking at improving person-centered outcomes. In this context the proposed clinical trial design will evaluate the efficacy of EGCG in the context of a personalized medicine approach that includes a multimodal intervention (nutritional, physical, cognitive and medical) looking at improving person-centered outcomes. Early phase I studies in Down syndrome young adults showed that while subjects were under EGCG, improvements in cognition were observed but these vanished when treatment was discontinued. Phase II studies combining EGCG with cognitive training showed improvements in cognitive performance and adaptive functionality but interestingly sustained effects after treatment discontinuation. Observations made in humans are in agreement with preclinical studies showing that EGCG combined with environmental enrichment resulted in an improvement of age-related cognitive decline. These observations are in favor of the option of combining EGCG with a personalized multimodal intervention. The personalized multimodal intervention will take into account medical comorbidities (i.e. metabolic syndrome, T2DM), diet (including nutritional status), physical exercise, and will incorporate cognitive training and a behavioral intervention to aid subject's adherence and empowerment to the intervention proposed. This will be in-line with other clinical studies in AD showing the superiority of multimodal interventions vs. a single life style intervention (i.e. single nutrient, physical activity). Hypothesis: A multimodal lifestyle change intervention (dietary, physical activity and cognition) combined with epigallocatechin gallate (EGCG) will slow down cognitive decline and improve brain connectivity in a population of participants with subjective cognitive decline (SCD).

Detailed Description

Study Design: Randomized, double-blind, personalized clinical trial with 150 subjects with subjective cognitive decline (SCD) of both genders, with 3 arms of treatment Duration of the Study: The total duration of the study is expected to be 24 months (subject recruitment, baseline period, treatment period, follow-up, data analysis, and study report).

Primary Objective(s): To evaluate the efficacy of a multimodal intervention (dietary, physical activity, and cognition) combined with epigallocatechin gallate (EGCG) in slowing down cognitive decline.

Secondary Objective(s): 1 To evaluate the safety of the interventions 2 To evaluate several underlying mechanisms that could explain the efficacy of the intervention in preventing the progression of cognitive decline: (i) Changes in brain connectivity, (ii) changes in AD biomarkers, (iii) changes in biomarkers of oxidation/inflammation, (iv) changes in gut microbiota composition and the metabolome derived by the action of microorganisms, v) changes in biological aging predictors.

Target Population: Subjects diagnosed with Subjective Cognitive Decline (SCD) criteria including cognitive performance within normal values (Normal scoring on psychometric evaluation, adjusted for age and education), carriers of the Apolipoprotein E4 allele, recruited either from either the Parc de Salut Mar and its primary care providers, from Barcelona Beta Brain Research Centre or through a web-based system.

Preselection criteria i.Adults aged 60-80 years with a BMI ≥18.5 and <32 kg/m2. ii. Ad-hoc Subjective Cognitive Decline Questionnaire (SCD-Q) item "do you perceive memory or cognitive difficulties?" positive.

iii. Subjects willing to participate and perform all study procedures, including Apolipoprotein E4 genotyping iv. The subject has one informant partner who, in the investigator's judgment has frequent and sufficient contact with the subject to provide accurate information about the subject's cognitive and functional abilities.

Study Arm(s):

1. Arm I: EGCG and multimodal intervention (n=50)

2. Arm II: Placebo EGCG and multimodal intervention (n=50)

3. Arm III: Healthy lifestyle recommendations (n=50) Duration of Patient Participation: The total duration of patient participation is expected to be 17 months. Run-in period (1 month): Basal assessment of cognitive performance (cognitive battery), diet and physical activity, daily living activities (self-reported tests), and mood (self-reported tests at basal assessment and EMA's). Interventions will last 12 months. Follow-up after intervention discontinuation: at least 3 months Treatment: EGCG (Font-UP, laboratories Grand Fontaine), a daily dose of approximately 5-6 mg/kg up to 500 mg/day will be administered to subjects for 12 months or a matched placebo Multimodal intervention (12 months): 1) Social stimulation, ten 90-120 minutes guided group activities; 2) Cognitive training, trice per week, 30-minute sessions; 3) Psychoeducational support groups, 10 sessions, 4) personalized diet 8 sessions, 5) personalized physical activity.

End point: modified Alzheimer Disease Cooperative Study Preclinical Alzheimer Cognitive Composite (ADCS-PACC), including additional tests of executive functions: the PACC-exe.

Conditions

Alzheimer Disease; Cognitive Decline

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

EGCG + multimodal intervention

EGCG + multimodal intervention (n=50) EGCG: (Font-UP, Laboratoires Grand Fontaine), a daily dose of 5-6 mg/kg up to 500 mg/day for 12 months

+ multimodal lifestyle personalized intervention

Group Type: EXPERIMENTAL

EGCG

Intervention Type: DIETARY_SUPPLEMENT

FontUp capsules (100 mg of EGCG each)

12 months, three to five capsules per day (participant's weight ≤ 50kg: 3 capsules/day; weight >50kg: 5 capsules/day.

Multimodal lifestyle intervention

Intervention Type: OTHER

• Dietary intervention: personalized dietary recommendations based on MedDiet, 9 individual counseling sessions.
• Physical activity intervention: Guided gymnasium (aerobic, strength, and balance activities). Minimum one class/week the first 6months, and two classes/week from month 7 to 12). Achieve a physically active lifestyle (10,000 steps/day; individuals living with disability 8,500 steps/day). Achieve moderate physical exercise in older adults (150 to 210 minutes/week or 90 to 150 minutes depending on medical history.
• Cognitive training: NeuronUP, 3/week, 30 min sessions
• Psychoeducation: ten 90-minute sessions
• Social stimulation activities: ten to twelve 90-to-120-minute sessions.

Placebo + multimodal intervention

Placebo Font-Up (n=50)

+ multimodal lifestyle personalized intervention

Group Type: PLACEBO_COMPARATOR

Placebo EGCG

Intervention Type: DIETARY_SUPPLEMENT

Placebo FontUp (same appearance as active).

12 months, three to five capsules per day (participant's weight ≤ 50kg: 3 capsules/day; weight >50kg: 5 capsules/day.

Multimodal lifestyle intervention

Intervention Type: OTHER

• Dietary intervention: personalized dietary recommendations based on MedDiet, 9 individual counseling sessions.
• Physical activity intervention: Guided gymnasium (aerobic, strength, and balance activities). Minimum one class/week the first 6months, and two classes/week from month 7 to 12). Achieve a physically active lifestyle (10,000 steps/day; individuals living with disability 8,500 steps/day). Achieve moderate physical exercise in older adults (150 to 210 minutes/week or 90 to 150 minutes depending on medical history.
• Cognitive training: NeuronUP, 3/week, 30 min sessions
• Psychoeducation: ten 90-minute sessions
• Social stimulation activities: ten to twelve 90-to-120-minute sessions.

Control

Healthy lifestyle recommendations (n=50)

Group Type: SHAM_COMPARATOR

Healthy lifestyle recommendations

Intervention Type: OTHER

Personalized advice on diet, physical activity, cognitive training, and social stimulation activities.

Interventions

EGCG

FontUp capsules (100 mg of EGCG each)

12 months, three to five capsules per day (participant's weight ≤ 50kg: 3 capsules/day; weight >50kg: 5 capsules/day.

Intervention Type: DIETARY_SUPPLEMENT

Placebo EGCG

Placebo FontUp (same appearance as active).

12 months, three to five capsules per day (participant's weight ≤ 50kg: 3 capsules/day; weight >50kg: 5 capsules/day.

Intervention Type: DIETARY_SUPPLEMENT

Healthy lifestyle recommendations

Personalized advice on diet, physical activity, cognitive training, and social stimulation activities.

Intervention Type: OTHER

Multimodal lifestyle intervention

• Dietary intervention: personalized dietary recommendations based on MedDiet, 9 individual counseling sessions.
• Physical activity intervention: Guided gymnasium (aerobic, strength, and balance activities). Minimum one class/week the first 6months, and two classes/week from month 7 to 12). Achieve a physically active lifestyle (10,000 steps/day; individuals living with disability 8,500 steps/day). Achieve moderate physical exercise in older adults (150 to 210 minutes/week or 90 to 150 minutes depending on medical history.
• Cognitive training: NeuronUP, 3/week, 30 min sessions
• Psychoeducation: ten 90-minute sessions
• Social stimulation activities: ten to twelve 90-to-120-minute sessions.

Intervention Type: OTHER

Eligibility Criteria

Exclusion Criteria

iii. Age between 60 and 80 with a BMI ≥18.5 and <35 kg/m2. iv. Carrying the APOE-ɛ4 allele. v. Participants are willing to participate and perform all study procedures.

i. Inability or unwillingness to give written informed consent or communicate with study staff or illiteracy.

ii. Clinically significant unstable psychiatric disorder that may affect cognition (e.g. major depression disorder, schizophrenia, bipolar or psychotic disorder according to DSM-V).

iii. Neurological conditions that may affect cognition or may imply a prodromal stage of neurodegenerative disease other than AD (e.g., cranioencephalic trauma with permanent neurologic effects, epilepsy, multiple sclerosis, previous stroke, extrapyramidal signs at physical exploration, history of brain tumor...).

iv. History or evidence of any medical condition or use of medication that in the opinion of the investigator could affect subjects' safety or interfere with the study assessments (e.g. use of neuroleptic drugs, anticonvulsant medications (except gabapentin and pregabalin for non-seizure indications) corticosteroids or immunosuppressive therapies that may affect inflammatory parameters).

v. Any contraindication to perform brain MRI (e.g. pacemaker, MRI-incompatible aneurysm clips).

vi. Clinically significant abnormalities in laboratory test or MRI scan results at screening unless acceptable by the investigator (e.g. mild/moderate kidney failure, benign tumor that does not require surgical intervention…).

vii. Any medical condition that may affect the study assessments in the opinion of the principal investigators or medical advisors.

viii. Current intake of vitamin supplements, catechins, or products containing EGCG (i.e. TEAVIGO, Mega Green Tea Capsules Life Extension, or Font-UP Grand Fontaine Laboratories) for at least 3 months previous to the screening visit.

ix. History within the last 2 years of treatment for primary or recurrent malignant disease, excluding non-melanoma skin cancers, resected cutaneous squamous cell carcinoma in situ, basal cell carcinoma, cervical carcinoma in situ, or situ prostate cancer with normal prostate-specific antigen post-treatment.

• Minimum Eligible Age: 60 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Hospital del Mar Research Institute

UNKNOWN

Sponsor Role: collaborator

Barcelonabeta Brain Research Center, Pasqual Maragall Foundation

OTHER

Sponsor Role: collaborator

Parc de Salut Mar

OTHER

Sponsor Role: lead

Responsible Party

Rafael de la Torre

Director Neurosciences Research Programme

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Barcelonabeta Brain Research Center

Barcelona, Barcelona, Spain, Spain

Hospital del Mar Research Institute Barcelona

Barcelona, , Spain

Countries

Spain

References

Skaper SD, Facci L, Zusso M, Giusti P. Synaptic Plasticity, Dementia and Alzheimer Disease. CNS Neurol Disord Drug Targets. 2017;16(3):220-233. doi: 10.2174/1871527316666170113120853.

Reference Type: BACKGROUND

PMID: 28088900 (View on PubMed)

Lopez-Sanz D, Bruna R, Garces P, Martin-Buro MC, Walter S, Delgado ML, Montenegro M, Lopez Higes R, Marcos A, Maestu F. Functional Connectivity Disruption in Subjective Cognitive Decline and Mild Cognitive Impairment: A Common Pattern of Alterations. Front Aging Neurosci. 2017 Apr 21;9:109. doi: 10.3389/fnagi.2017.00109. eCollection 2017.

Reference Type: BACKGROUND

PMID: 28484387 (View on PubMed)

Mandolesi L, Gelfo F, Serra L, Montuori S, Polverino A, Curcio G, Sorrentino G. Environmental Factors Promoting Neural Plasticity: Insights from Animal and Human Studies. Neural Plast. 2017;2017:7219461. doi: 10.1155/2017/7219461. Epub 2017 Jun 14.

Reference Type: BACKGROUND

PMID: 28740740 (View on PubMed)

Galvin JE. Prevention of Alzheimer's Disease: Lessons Learned and Applied. J Am Geriatr Soc. 2017 Oct;65(10):2128-2133. doi: 10.1111/jgs.14997. Epub 2017 Aug 2.

Reference Type: BACKGROUND

PMID: 28766695 (View on PubMed)

De la Torre R, De Sola S, Pons M, Duchon A, de Lagran MM, Farre M, Fito M, Benejam B, Langohr K, Rodriguez J, Pujadas M, Bizot JC, Cuenca A, Janel N, Catuara S, Covas MI, Blehaut H, Herault Y, Delabar JM, Dierssen M. Epigallocatechin-3-gallate, a DYRK1A inhibitor, rescues cognitive deficits in Down syndrome mouse models and in humans. Mol Nutr Food Res. 2014 Feb;58(2):278-88. doi: 10.1002/mnfr.201300325. Epub 2013 Sep 14.

Reference Type: BACKGROUND

PMID: 24039182 (View on PubMed)

de la Torre R, de Sola S, Hernandez G, Farre M, Pujol J, Rodriguez J, Espadaler JM, Langohr K, Cuenca-Royo A, Principe A, Xicota L, Janel N, Catuara-Solarz S, Sanchez-Benavides G, Blehaut H, Duenas-Espin I, Del Hoyo L, Benejam B, Blanco-Hinojo L, Videla S, Fito M, Delabar JM, Dierssen M; TESDAD study group. Safety and efficacy of cognitive training plus epigallocatechin-3-gallate in young adults with Down's syndrome (TESDAD): a double-blind, randomised, placebo-controlled, phase 2 trial. Lancet Neurol. 2016 Jul;15(8):801-810. doi: 10.1016/S1474-4422(16)30034-5.

Reference Type: BACKGROUND

PMID: 27302362 (View on PubMed)

Pons-Espinal M, Martinez de Lagran M, Dierssen M. Environmental enrichment rescues DYRK1A activity and hippocampal adult neurogenesis in TgDyrk1A. Neurobiol Dis. 2013 Dec;60:18-31. doi: 10.1016/j.nbd.2013.08.008. Epub 2013 Aug 20.

Reference Type: BACKGROUND

PMID: 23969234 (View on PubMed)

Catuara-Solarz S, Espinosa-Carrasco J, Erb I, Langohr K, Notredame C, Gonzalez JR, Dierssen M. Principal Component Analysis of the Effects of Environmental Enrichment and (-)-epigallocatechin-3-gallate on Age-Associated Learning Deficits in a Mouse Model of Down Syndrome. Front Behav Neurosci. 2015 Dec 11;9:330. doi: 10.3389/fnbeh.2015.00330. eCollection 2015.

Reference Type: BACKGROUND

PMID: 26696850 (View on PubMed)

McEwen SC, Siddarth P, Rahi B, Kim Y, Mui W, Wu P, Emerson ND, Lee J, Greenberg S, Shelton T, Kaiser S, Small GW, Merrill DA. Simultaneous Aerobic Exercise and Memory Training Program in Older Adults with Subjective Memory Impairments. J Alzheimers Dis. 2018;62(2):795-806. doi: 10.3233/JAD-170846.

Reference Type: BACKGROUND

PMID: 29480182 (View on PubMed)

Prince M, Comas-Herrera A, Knapp M, Guerchet M, Karagiannidou M. World Alzheimer Report 2016 Improving healthcare for people living with dementia. Coverage, Quality and costs now and in the future. Alzheimer's Disease International (ADI). London; 2016.

Reference Type: BACKGROUND

Livingston G, Sommerlad A, Orgeta V, Costafreda SG, Huntley J, Ames D, Ballard C, Banerjee S, Burns A, Cohen-Mansfield J, Cooper C, Fox N, Gitlin LN, Howard R, Kales HC, Larson EB, Ritchie K, Rockwood K, Sampson EL, Samus Q, Schneider LS, Selbaek G, Teri L, Mukadam N. Dementia prevention, intervention, and care. Lancet. 2017 Dec 16;390(10113):2673-2734. doi: 10.1016/S0140-6736(17)31363-6. Epub 2017 Jul 20. No abstract available.

Reference Type: BACKGROUND

PMID: 28735855 (View on PubMed)

Buckley RF, Maruff P, Ames D, Bourgeat P, Martins RN, Masters CL, Rainey-Smith S, Lautenschlager N, Rowe CC, Savage G, Villemagne VL, Ellis KA; AIBL study. Subjective memory decline predicts greater rates of clinical progression in preclinical Alzheimer's disease. Alzheimers Dement. 2016 Jul;12(7):796-804. doi: 10.1016/j.jalz.2015.12.013. Epub 2016 Feb 4.

Reference Type: BACKGROUND

PMID: 26852195 (View on PubMed)

Ngandu T, Lehtisalo J, Solomon A, Levalahti E, Ahtiluoto S, Antikainen R, Backman L, Hanninen T, Jula A, Laatikainen T, Lindstrom J, Mangialasche F, Paajanen T, Pajala S, Peltonen M, Rauramaa R, Stigsdotter-Neely A, Strandberg T, Tuomilehto J, Soininen H, Kivipelto M. A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): a randomised controlled trial. Lancet. 2015 Jun 6;385(9984):2255-63. doi: 10.1016/S0140-6736(15)60461-5. Epub 2015 Mar 12.

Reference Type: BACKGROUND

PMID: 25771249 (View on PubMed)

Crous-Bou M, Minguillon C, Gramunt N, Molinuevo JL. Alzheimer's disease prevention: from risk factors to early intervention. Alzheimers Res Ther. 2017 Sep 12;9(1):71. doi: 10.1186/s13195-017-0297-z.

Reference Type: BACKGROUND

PMID: 28899416 (View on PubMed)

Vellas B, Carrie I, Gillette-Guyonnet S, Touchon J, Dantoine T, Dartigues JF, Cuffi MN, Bordes S, Gasnier Y, Robert P, Bories L, Rouaud O, Desclaux F, Sudres K, Bonnefoy M, Pesce A, Dufouil C, Lehericy S, Chupin M, Mangin JF, Payoux P, Adel D, Legrand P, Catheline D, Kanony C, Zaim M, Molinier L, Costa N, Delrieu J, Voisin T, Faisant C, Lala F, Nourhashemi F, Rolland Y, Van Kan GA, Dupuy C, Cantet C, Cestac P, Belleville S, Willis S, Cesari M, Weiner MW, Soto ME, Ousset PJ, Andrieu S. MAPT STUDY: A MULTIDOMAIN APPROACH FOR PREVENTING ALZHEIMER'S DISEASE: DESIGN AND BASELINE DATA. J Prev Alzheimers Dis. 2014 Jun;1(1):13-22.

Reference Type: BACKGROUND

PMID: 26594639 (View on PubMed)

Andrieu S, Guyonnet S, Coley N, Cantet C, Bonnefoy M, Bordes S, Bories L, Cufi MN, Dantoine T, Dartigues JF, Desclaux F, Gabelle A, Gasnier Y, Pesce A, Sudres K, Touchon J, Robert P, Rouaud O, Legrand P, Payoux P, Caubere JP, Weiner M, Carrie I, Ousset PJ, Vellas B; MAPT Study Group. Effect of long-term omega 3 polyunsaturated fatty acid supplementation with or without multidomain intervention on cognitive function in elderly adults with memory complaints (MAPT): a randomised, placebo-controlled trial. Lancet Neurol. 2017 May;16(5):377-389. doi: 10.1016/S1474-4422(17)30040-6. Epub 2017 Mar 27.

Reference Type: BACKGROUND

PMID: 28359749 (View on PubMed)

Moll van Charante EP, Richard E, Eurelings LS, van Dalen JW, Ligthart SA, van Bussel EF, Hoevenaar-Blom MP, Vermeulen M, van Gool WA. Effectiveness of a 6-year multidomain vascular care intervention to prevent dementia (preDIVA): a cluster-randomised controlled trial. Lancet. 2016 Aug 20;388(10046):797-805. doi: 10.1016/S0140-6736(16)30950-3. Epub 2016 Jul 26.

Reference Type: BACKGROUND

PMID: 27474376 (View on PubMed)

Kivipelto M, Solomon A, Ahtiluoto S, Ngandu T, Lehtisalo J, Antikainen R, Backman L, Hanninen T, Jula A, Laatikainen T, Lindstrom J, Mangialasche F, Nissinen A, Paajanen T, Pajala S, Peltonen M, Rauramaa R, Stigsdotter-Neely A, Strandberg T, Tuomilehto J, Soininen H. The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER): study design and progress. Alzheimers Dement. 2013 Nov;9(6):657-65. doi: 10.1016/j.jalz.2012.09.012. Epub 2013 Jan 17.

Reference Type: BACKGROUND

PMID: 23332672 (View on PubMed)

Valls-Pedret C, Lamuela-Raventos RM, Medina-Remon A, Quintana M, Corella D, Pinto X, Martinez-Gonzalez MA, Estruch R, Ros E. Polyphenol-rich foods in the Mediterranean diet are associated with better cognitive function in elderly subjects at high cardiovascular risk. J Alzheimers Dis. 2012;29(4):773-82. doi: 10.3233/JAD-2012-111799.

Reference Type: BACKGROUND

PMID: 22349682 (View on PubMed)

Martinez-Lapiscina EH, Clavero P, Toledo E, San Julian B, Sanchez-Tainta A, Corella D, Lamuela-Raventos RM, Martinez JA, Martinez-Gonzalez MA. Virgin olive oil supplementation and long-term cognition: the PREDIMED-NAVARRA randomized, trial. J Nutr Health Aging. 2013;17(6):544-52. doi: 10.1007/s12603-013-0027-6.

Reference Type: BACKGROUND

PMID: 23732551 (View on PubMed)

Valls-Pedret C, Sala-Vila A, Serra-Mir M, Corella D, de la Torre R, Martinez-Gonzalez MA, Martinez-Lapiscina EH, Fito M, Perez-Heras A, Salas-Salvado J, Estruch R, Ros E. Mediterranean Diet and Age-Related Cognitive Decline: A Randomized Clinical Trial. JAMA Intern Med. 2015 Jul;175(7):1094-1103. doi: 10.1001/jamainternmed.2015.1668.

Reference Type: BACKGROUND

PMID: 25961184 (View on PubMed)

Morris MC, Tangney CC, Wang Y, Sacks FM, Barnes LL, Bennett DA, Aggarwal NT. MIND diet slows cognitive decline with aging. Alzheimers Dement. 2015 Sep;11(9):1015-22. doi: 10.1016/j.jalz.2015.04.011. Epub 2015 Jun 15.

Reference Type: BACKGROUND

PMID: 26086182 (View on PubMed)

Morris MC, Tangney CC, Wang Y, Sacks FM, Bennett DA, Aggarwal NT. MIND diet associated with reduced incidence of Alzheimer's disease. Alzheimers Dement. 2015 Sep;11(9):1007-14. doi: 10.1016/j.jalz.2014.11.009. Epub 2015 Feb 11.

Reference Type: BACKGROUND

PMID: 25681666 (View on PubMed)

Other Identifiers

IMIM/PENSA

Identifier Type: -

Identifier Source: org_study_id