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).

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.

Inclusion Criteria:

i. Meet all selection criteria and no exclusion criteria. ii. Fulfill SCD criteria (Jessen et al. 2014) including cognitive performance within normal values (Normal scoring on psychometric evaluation, adjusted for age and education).

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.

Exclusion Criteria:

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.

Randomized, double-blind clinical trial (participant, investigator, outcomes assessor)