- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03978052
Prevention of Cognitive Decline in ApoE4 Carriers With Subjective Cognitive Decline After EGCG and a Multimodal Intervention ((PENSA))
Study Overview
Status
Conditions
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):
- Arm I: EGCG and multimodal intervention (n=50)
- Arm II: Placebo EGCG and multimodal intervention (n=50)
- 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.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
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Barcelona, Spain, 08003
- Hospital del Mar Research Institute Barcelona
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Barcelona, Spain
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Barcelona, Barcelona, Spain, Spain, 08005
- BarcelonaBeta Brain Research Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: 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 |
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.
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Placebo Comparator: Placebo + multimodal intervention
Placebo Font-Up (n=50) + multimodal lifestyle personalized intervention |
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. |
Sham Comparator: Control
Healthy lifestyle recommendations (n=50)
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Personalized advice on diet, physical activity, cognitive training, and social stimulation activities.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Modified Alzheimer Disease Cooperative Study Preclinical Alzheimer Cognitive Composite (ADCS-PACC) including additional tests of executive functions: the PACC-exe
Time Frame: Screening and 12 months
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Changes in the PACC-exe, that include: The Total Recall score from the Free and Cued Selective Reminding Test (FCSRT) (which range from 0-48 words),The Delayed Recall score on the Logical Memory IIa subtest from the Wechsler Memory Scale (which range from 0-25 story units), the Coding Test Total score from the Wechsler Adult Intelligence Scale-Revised (which range from 0-93 symbols), The Montreal Cognitive assessment (MOCA) total score (which range from 0-30 points), and additionally, the Interference score from the Stroop Colour and Word Test (SCWT) and the Five Digit Test. Each of the component change scores is divided by the baseline sample standard deviation of that component, to form standardized z scores. These z scores are summed to form the composite. |
Screening and 12 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Changes in Functional neuronal connectivity (assessed by a functional magnetic resonance imaging)
Time Frame: Screening and 12 months.
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Changes in Maps of change in connectivity of the Default mode network Changes in Maps of change in connectivity of the Limbic network Changes in Maps of change in connectivity of the Salience network
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Screening and 12 months.
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Changes in structural connectivity networks known to be affected in Alzheimer Disease
Time Frame: Screening and 12 months.
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Changes in Connectivity changes of the parahippocampus/fornix Changes in Connectivity changes of the cingulum/cingulate fiber bundle Changes in connectivity changes of the caudate heads
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Screening and 12 months.
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Safety outcome of the intervention with EGCG: AEs and SAEs
Time Frame: Baseline, 6 and 12
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evaluated by means of Incidence, nature, severity and causality of adverse events (AEs) and serious adverse events (SAEs)
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Baseline, 6 and 12
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Safety outcome of the intervention with EGCG: Biomarkers thyroid
Time Frame: Baseline, 6 and 12
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Assessment of thyroid function parameters: both TSH and freeT4 within normal values according to the reference population
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Baseline, 6 and 12
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Safety outcome of the intervention with EGCG: Biomarkers liver
Time Frame: Baseline, 6 and 12
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Assessment of liver function parameters: ALP and ALT within normal values according to the reference population
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Baseline, 6 and 12
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Safety outcome of the intervention with EGCG: Biomarkers
Time Frame: Baseline, 6 and 12
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Assessment of renal function parameters: creatinine within normal values according to the reference population
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Baseline, 6 and 12
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Changes in the semantic verbal fluency
Time Frame: Baseline, 6, 12 and 15 months
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Changes in additional cognitive performance scores of: (i) Semantic verbal fluency, "animals" in one minute.
(which range from 0-12 words) higher score is better outcome.
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Baseline, 6, 12 and 15 months
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Changes in the Olfactory function
Time Frame: Baseline, and 12 months
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Changes in the Olfactory function: the University of Pennsylvania Smell Identification Test (UPSIT) is designed to test the function of an individual's olfactory system.
It is the gold standard of smell identification tests.
Its performance has been related to cognition and it has been widely used as a complementary assessment tool in dementia patients.(
which range from 0-40)
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Baseline, and 12 months
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Changes in Modified Alzheimer Disease Cooperative Study Preclinical Alzheimer Cognitive Composite (ADCS-PACC) including additional tests of executive functions: the PACC-exe
Time Frame: Screening, 6, 12 and 15 months.
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Changes in the PACC-exe, that include: The Total Recall score from the Free and Cued Selective Reminding Test (FCSRT) (which range from 0-48 words),The Delayed Recall score on the Logical Memory IIa subtest from the Wechsler Memory Scale (which range from 0-25 story units), the Coding Test Total score from the Wechsler Adult Intelligence Scale-Revised (which range from 0-93 symbols), The Montreal Cognitive assessment (MOCA) total score (which range from 0-30 points), and additionally, the Interference score from the Stroop Colour and Word Test (SCWT) and the Five Digit Test. Each of the component change scores is divided by the baseline sample standard deviation of that component, to form standardized z scores. These z scores are summed to form the composite. |
Screening, 6, 12 and 15 months.
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Changes in the microbiota composition
Time Frame: Baseline, and 12 months.
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For the analysis of microbiota biomarkers our characterization of the microbiome of the samples will include determination of the levels of biodiversity in the samples.
Samples will be divided into quartiles in order to label each sample as having low (1st quartile), average (2nd and 3rd quartiles), or high diversity (4th quartile).
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Baseline, and 12 months.
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Change in the dietary patterns (metabolomics) Plasma samples
Time Frame: Baseline, 6, 12 and 15 months
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Change in the dietary patterns (metabolomics).
Plasma, samples will be collected to analyze the corresponding metabolomes (SFCAs, kynurenine pathway...), we will divide samples into quartiles to label each sample as having low (1st quartile), average (2nd and 3rd quartiles), or high diversity (4th quartile)
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Baseline, 6, 12 and 15 months
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Change in the dietary patterns (metabolomics) oral fluid
Time Frame: Baseline, 6, 12 and 15 months
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Changes in the dietary patterns (metabolomics) of oral fluid will be collected to analyze the corresponding metabolomes for a better understanding of the complexity of the interrelationship of metabolomics in oral fluid and mental health.
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Baseline, 6, 12 and 15 months
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Change in the dietary patterns (metabolomics). urinary samples
Time Frame: Baseline, 6, 12 and 15 months
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Change in the dietary patterns (metabolomics).
urinary samples will be collected to analyze the corresponding metabolomes for a better understanding of the complexity of the interrelationship of microbiota, diet, and mental health.
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Baseline, 6, 12 and 15 months
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Exploratory
Time Frame: At 6 and 12 months
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Change in metabolomes derived from the treatment compliance after a multimodal lifestyle change intervention.
Urinary samples (24h) will be used to identify objective biomarkers of dietary intake and dietary patterns and to assess the degree of adherence to the Mediterranean diet by monitoring the levels of dietary metabolites (i.e.
hydroxytyrosol metabolism, biomarkers of alcohol consumption...).
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At 6 and 12 months
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Changes in the Boston Naming Test
Time Frame: Baseline, 6, 12 and 15 months
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Changes in additional cognitive performance scores of: (ii) naming, Boston Naming Test (BNT).: (which range from 0-15 points) higher score is better outcome.
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Baseline, 6, 12 and 15 months
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Change in attention and working memory
Time Frame: Baseline, 6, 12 and 15 months
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Changes in additional cognitive performance scores of: (iii) attention and working memory,
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Baseline, 6, 12 and 15 months
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Change in the Digit span subtest (WAIS IV)
Time Frame: Baseline, 6, 12 and 15 months
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Changes in additional cognitive performance scores of: (iv) Digit span subtest (WAIS IV) , (which range from 0-16 points)
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Baseline, 6, 12 and 15 months
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Changes in the AD biomarkers
Time Frame: Baseline, and 12 months
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Changes in the AD biomarkers related to neurodegeneration (NfL), neurotoxicity (GFAP),Tau proteins amyloid-β peptides
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Baseline, and 12 months
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Changes in biological aging
Time Frame: Baseline and 12 months
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Blood sample will be collected for further analysis on biological age biomarkers assessed by epigenetics (biological ageing).
The difference between chronological age and biological age, defined as average age acceleration (Δage), will be used to determine individual aging.
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Baseline and 12 months
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Changes in physical activity/fitness: VREM
Time Frame: Screening, 6, 12 and 15 months
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Changes in physical activity as measured by the Spanish Short Version of the Minnesota Leisure Time Physical Activity Questionnaire (Comellas et al., 2012).
It reports energy expenditure during leisure time and allows individuals to be classified into activity categories.
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Screening, 6, 12 and 15 months
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Changes in physical activity/fitness: RAPA
Time Frame: Screening, 6, 12 and 15 months
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Changes in physical activity as measured by the Rapid Assessment of Physical Activity (RAPA).
Designed for quickly assessing the level of physical activity of older adults.
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Screening, 6, 12 and 15 months
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Changes in physical activity/fitness: SPPB
Time Frame: Screening, 6, 12 and 15 months
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Changes in physical performance as measured by The Short Physical Performance Battery (SPPB), a validated measure of physical function in older adults.
The SPPB represents the sum of results from three component tests of functional relevance: standing balance, 4-meter gait speed (4MGS), and five-repetition sit-to-stand motion (5STS)
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Screening, 6, 12 and 15 months
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Changes in physical activity/fitness: SFT
Time Frame: Screening, 6, 12
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Changes in physical performance as measured by the The Senior Fitness Test battery evaluating balance (flamingo test), lower limb strength (chair stand test), upper limb strength (arm curl test), lower limb flexibility (chair sit-and-reach test), upper limb flexibility (back scratch test), agility (8-foot up-and-go test), speed (brisk walking test) and resistance (6-minute walk test).
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Screening, 6, 12
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Changes in physical activity/fitness: grip strength
Time Frame: Screening, 6, 12 and 15 months
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Changes in physical performance as measured by the grip strength with a dynamometer, which measures the maximum isometric strength of the hand and forearm muscles.
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Screening, 6, 12 and 15 months
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Changes in physical activity/fitness: Fitbit steps
Time Frame: Screening, 6, 12 and 15 months or continuous measures (Fitbit measures and EMAs)
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Changes in physical activity as measured by the number of steps
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Screening, 6, 12 and 15 months or continuous measures (Fitbit measures and EMAs)
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Changes in physical activity/fitness: Fitbit physical activity
Time Frame: Continuous measure
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Changes in physical activity as measured by the physical activity estimation.
Each minute is classified as being sedentary, light, moderate or vigorous activity, based on metabolic equivalent (METs), which are indicators for exercise intensity.
After 10 minutes of continuous moderate to intense activity, equivalent for activities at or above 3 METs, such minutes are considered "active minutes".
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Continuous measure
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Changes in physical activity/fitness: Fitbit floors climbed
Time Frame: Continuous measure
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Changes in physical activity as measured by the number of floors climbed
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Continuous measure
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Changes in physical activity/fitness: Fitbit active minutes
Time Frame: Continuous measure
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Changes in physical activity as measured by the number of active minutes
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Continuous measure
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Changes in physical activity/fitness: Fitbit heart rate
Time Frame: Continuous measure
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Changes in physical activity as measured by the heart rate
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Continuous measure
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Changes in quality of sleep: Fitbit sleep
Time Frame: Continuous measure
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Changes in sleep as measured by the sleep duration
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Continuous measure
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Changes in quality of sleep: Pittsburg Sleep Quality Index
Time Frame: Screening, 6, 12 and 15 months
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Changes in sleep measured by the Pittsburg Sleep Quality Index: provides a global index of sleep quality over the previous one-month interval.
It is a generic, 19 items self-rated scale designed to measure overall sleep problems
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Screening, 6, 12 and 15 months
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Changes in quality of sleep: Epworth sleepines scale
Time Frame: Screening, 6, 12 and 15 months
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Changes in sleep Epworth sleepiness scale (ESS): The ESS assesses daytime sleepiness.
It is a four-grade scale (0, no napping; 3, high likelihood of napping), with eight questions, with a maximum of 24 points; a score >10 is considered to be excessive sleepiness.
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Screening, 6, 12 and 15 months
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Treatment compliance/adherence: EGCG
Time Frame: Screening, 6 and 12 months
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As a biomarker of EGCG ingestion compliance, EGCG will determined in plasma samples by HPLC/MS/MS at 6 and 12 months.
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Screening, 6 and 12 months
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Treatment adherence: Diet
Time Frame: Screening, 6 and 12 months
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Compliance/adherence with diet will be assessed by means of 3-day food diaries
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Screening, 6 and 12 months
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Treatment compliance/adherence: mental health
Time Frame: Screening, 6 and 12 months
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Adherence to mental health interventions will be assessed through means of: (i) monitoring the attendance to the psychoeducational group sessions, (ii) monitoring the attendance to the monthly cognitive stimulation activities, and (iii) monitoring the attendance to the scheduled cognitive training sessions (NeuronUp).
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Screening, 6 and 12 months
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Treatment compliance/adherence: MedDiet-index
Time Frame: Screening, 6 and 12 months
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Compliance/adherence with diet will be assessed by means of the 14-item Mediterranean Diet adherence screener (Martínez-González MA et al. 2012)
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Screening, 6 and 12 months
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Treatment compliance/adherence: Diet MNA
Time Frame: Screening, 6 and 12 months
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Compliance/adherence diet as assessed by the Mini Nutritional Assessment test (MNA), a single, rapid assessment of nutritional status in elderly patients in outpatient clinics, hospitals, and nursing homes.
The MNA test is composed of simple measurements and brief questions that can be completed in about 10 min.
The sum of the MNA score distinguishes between elderly patients with: 1) adequate nutritional status, MNA > or = 24; 2) protein-calorie malnutrition, MNA < 17; 3) at risk of malnutrition.
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Screening, 6 and 12 months
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Changes in adaptive behaviour: ABAS-2
Time Frame: Screening, 6, 12 and 15 months
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Changes in adaptive behavior as measured by the Adaptive Behavior Assessment System - Second Edition -ABAS-II- for adults.
The ABAS-II tool for adults (ages 16 to 89) includes 5 subscales which assess the individual's competence (in terms of behavior frequency) in 10 different skill areas: communication abilities, community use, functional academics, home living, health and safety, leisure, self-care, self-direction, social interaction and working/labor skills
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Screening, 6, 12 and 15 months
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Changes in Quality of Life: EQ-5D-5L
Time Frame: Screening, 6, 12 and 15 months
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Changes in quality of Life as measured by the EuroQol 5 dimensions 5 levels (EQ-5D-5L) the most used econometric instrument in the world.
It is a generic instrument, applicable both in the general population and in patients with different conditions.
It contains 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.
It generates a single score that incorporates society's preferences for health states (utilities), suitable for cost-utility analysis by calculating quality-adjusted life years (QALYs).
The health index range from 1 (perfect health) to negative values (for those states considered worse than death), 0 being the value assigned to death.
The EQ-5D-5L has been validated in the Spanish population
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Screening, 6, 12 and 15 months
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Changes in quality of life: WHOQOL-BREF
Time Frame: Screening, 6, 12 and 15 months
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Changes in quality of life measured by the the World Health Organization brief generic questionnaire (WHOQOL-BREF), a cross-cultural instrument to assess quality of life.
It assesses the following broad domains: physical health, psychological health, social relationships, and environment
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Screening, 6, 12 and 15 months
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Collaborators and Investigators
Publications and helpful links
General Publications
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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. Erratum In: J Alzheimers Dis. 2019;67(3):1107.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
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Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Mental Disorders
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Neurocognitive Disorders
- Neurodegenerative Diseases
- Dementia
- Tauopathies
- Cognition Disorders
- Alzheimer Disease
- Cognitive Dysfunction
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Neuroprotective Agents
- Protective Agents
- Antioxidants
- Anticarcinogenic Agents
- Antimutagenic Agents
- Epigallocatechin gallate
Other Study ID Numbers
- IMIM/PENSA
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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