An interventional study of High load and Moderate load in Alzheimer's Dementia (AD) and Alzheimer Disease (AD), sponsored by European University Miguel de Cervantes. Not yet recruiting at 1 site in Spain. Open to participants aged 60 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-11-05.
Sponsored by European University Miguel de Cervantes · Not applicable, Interventional, and Health services research
Alzheimer's disease (AD) is the leading cause of dementia worldwide and involves systemic alterations beyond the brain, such as loss of muscle strength, chronic low-grade inflammation, and gut microbiome dysbiosis. Physical exercise is a promising non-pharmacological therapy, and velocity-based resistance training has proven safe and effective in older adults. However, the effects of performing resistance exercises at high versus moderate velocity in people with AD remain unknown, and human evidence on how exercise modulates the gut microbiome in AD is very limited. This study aims to assess and compare the effects of two velocity-based resistance training modalities (high load at moderate velocity and moderate load at high velocity) versus usual care on the gut microbiome, systemic inflammation, plasma biomarkers, biological age, and intrinsic capacity in older adults with mild-to-moderate AD, using cognitively healthy older adults as a reference group.
Alzheimer's disease (AD) is the leading cause of dementia worldwide, affecting more than 50 million people, a figure projected to exceed 150 million by 2050, with a high economic and social burden that increases with disease severity. Beyond the accumulation of amyloid-β and hyperphosphorylated tau in the brain, AD involves systemic alterations even in early stages, including the progressive loss of muscle mass and strength (sarcopenia), chronic low-grade inflammation and disruption of the gut-brain axis. In this context, physical exercise has emerged as a high-impact adjuvant therapy capable of inducing relevant neurobiological and systemic adaptations. Among the available training modalities, velocity-based resistance training (i.e., controlling the execution velocity of each repetition to individualize the training load) has been shown to be safe and effective in older adults. However, the effects of executing resistance exercises at high velocity with moderate loads (e.g., 40-60% of one-repetition maximum [1RM]) versus moderate velocity with high loads (e.g., 60-80% 1RM) remain unexplored in people with AD. These exercise-induced adaptations can be monitored through circulating biomarkers that capture different biological responses: brain-derived neurotrophic factor (BDNF), a key mediator of neuronal survival and synaptic plasticity; the testosterone/cortisol ratio, an indicator of anabolic-catabolic balance; phosphorylated tau 217 (p-tau217), one of the most specific plasma markers of AD pathology; and Klotho, a protein linked to healthy aging with neuroprotective and anti-inflammatory functions. In parallel, the gut microbiome has gained prominence as a key modulator of the muscle-gut-brain axis. People with AD show reduced microbial diversity, an expansion of pro-inflammatory species and a reduction of short-chain fatty acid-producing bacteria, which compromise intestinal and blood-brain barrier integrity and amplify systemic inflammation. Although animal models consistently show that exercise promotes beneficial taxa and is associated with cognitive improvements, human studies have focused mainly on healthy older adults, and evidence in people diagnosed with AD is very limited. Moreover, molecular changes should translate into clinically relevant benefits. The World Health Organization's intrinsic capacity framework (cognition, locomotion, vitality, psychological and sensory domains) offers an integrative approach linking biological mechanisms with functional outcomes, together with sarcopenia, frailty, functional independence and caregiver burden. Therefore, this randomized controlled trial will compare two velocity-based resistance training modalities with usual care in older adults with mild-to-moderate AD, including a cognitively healthy reference group, to determine which modality has the greatest impact on the muscle-gut-brain axis, biological aging and intrinsic capacity, and whether these effects persist after detraining.
3,965 studies on the registry are indexed under Alzheimer Disease; 926 are open to participants now.
This study's planned enrollment of 48 is below the median of 70 across 3,019 interventional studies indexed under Alzheimer Disease.
Browse Alzheimer Disease studies →European University Miguel de Cervantes is the lead sponsor of 15 studies on the registry; 8 are open to participants now.
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Inclusion Criteria - participants with Alzheimer's Disease
Inclusion Criteria - cognitively healthy reference group
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants with mild-to-moderate AD perform 12 weeks of supervised based resistance training at 60-80% 1RM, 3 sessions/week, plus usual care. Followed by 12 weeks of detraining.
Other: High load
Participants with mild-to-moderate AD perform 12 weeks of supervised based resistance training at 40-60% 1RM, 3 sessions/week, plus usual care. Followed by 12 weeks of detraining.
Other: Moderate load
Participants with mild-to-moderate AD continue their usual care only (cognitive therapy, music therapy or other routine therapies).
Cognitively healthy adults aged ≥ 60 years, not randomized for the longitudinal phase and not undergoing structured exercise. At week 1 they will be randomized to a single high-load session, a single moderate-load session or no exercise for the acute sub-study.
Other: Healthy adults - High load · Other: Healthy adults - Moderate load
Supervised resistance training programme lasting 12 weeks, with 3 sessions per week of 60 minutes each. Each session consists of a 15-minute mobility warm-up, in which one set of 10 repetitions with a load of 10% of body weight is performed for each exercise; a 35-minute main part with five exercises performed on guided resistance machines (leg press, leg extension, leg curl, chest press and seated row) in circuit format at 60-80% of one-repetition maximum (1RM); and a 10-minute cool-down with mobility and flexibility exercises. Training volume will be progressively increased throughout the programme by increasing the number of repetitions and sets per exercise.
Supervised resistance training programme lasting 12 weeks, with 3 sessions per week of 60 minutes each. Each session consists of a 15-minute mobility warm-up, in which one set of 10 repetitions with a load of 10% of body weight is performed for each exercise; a 35-minute main part with five exercises performed on guided resistance machines (leg press, leg extension, leg curl, chest press and seated row) in circuit format at 40-60% of one-repetition maximum (1RM); and a 10-minute cool-down with mobility and flexibility exercises. Training volume will be progressively increased throughout the programme by increasing the number of repetitions and sets per exercise.
One acute session of 60 minutes each. The session consists of a 15-minute mobility warm-up, in which one set of 10 repetitions with a load of 10% of body weight is performed for each exercise; a 35-minute main part with five exercises performed on guided resistance machines (leg press, leg extension, leg curl, chest press and seated row) in circuit format at 60% of one-repetition maximum (1RM); and a 10-minute cool-down with mobility and flexibility exercises.
One acute session of 60 minutes each. The session consists of a 15-minute mobility warm-up, in which one set of 10 repetitions with a load of 10% of body weight is performed for each exercise; a 35-minute main part with five exercises performed on guided resistance machines (leg press, leg extension, leg curl, chest press and seated row) in circuit format at 40% of one-repetition maximum (1RM); and a 10-minute cool-down with mobility and flexibility exercises.
Gut microbiome
Participants will collect a stool sample at home using a commercial collection kit (REAL Stool Sample Collection Microbiome kit, Durviz S.L., Valencia, Spain). Samples will be divided into three aliquots and stored at -80ºC within 2 hours of collection. Microbial DNA will be extracted and the gut microbiome will be analysed by next-generation sequencing of the 16S rRNA gene.
Time frame: Baseline, week 12 of intervention
Inflammation indices - Systemic Inflammation Response Index
Fasting venous blood samples will be collected by a qualified nurse from the antecubital vein and complete blood count will be assessed by flow cytometry to assess the Systemic Inflammation Response Index (SIRI) . SIRI = (neutrophils × monocytes) / lymphocytes All cell counts will be expressed as ×10⁹ cells/L or equivalent.
Time frame: Baseline, week 1 of intervention, week 12 of intervention and week 12 of detraining
Plasma biomarkers - Brain-derived neurotrophic factor
Plasma concentrations of Brain-derived neutrophic factor (BDNF) will be measured by Enzyme-Linked ImmunoSorbent Assay (ELISA). Fasting venous blood samples will be collected by a qualified nurse from the antecubital vein into EDTA-treated vacutainers and centrifuged at 1500g for 10 minutes. Plasma will then undergo a second centrifugation at 2500g for 15 minutes and be stored in cryogenic vials at -80ºC. Results will be expressed in pg/mL or ng/mL.
Time frame: Baseline, week 1 of intervention, week 12 of intervention and week 12 of detraining
Inflammation indices - Aggregate Index of Systemic Inflammation
Fasting venous blood samples will be collected by a qualified nurse from the antecubital vein and complete blood count will be assessed by flow cytometry to assess the Aggregate Index of Systemic Inflammation (AISI). AISI = (neutrophils × monocytes × platelets) / lymphocytes All cell counts will be expressed as ×10⁹ cells/L or equivalent.
Time frame: Baseline, week 1 of intervention, week 12 of intervention and week 12 of detraining
Plasma biomarkers - p-tau217
Plasma concentrations of p-tau217 will be measured by ELISA. Fasting venous blood samples will be collected by a qualified nurse from the antecubital vein into EDTA-treated vacutainers and centrifuged at 1500g for 10 minutes. Plasma will then undergo a second centrifugation at 2500g for 15 minutes and be stored in cryogenic vials at -80ºC. Results will be expressed in pg/mL or ng/mL.
Time frame: Baseline, week 1 of intervention, week 12 of intervention and week 12 of detraining
Plasma biomarkers - Klotho
Plasma concentrations of klotho will be measured by ELISA. Fasting venous blood samples will be collected by a qualified nurse from the antecubital vein into EDTA-treated vacutainers and centrifuged at 1500g for 10 minutes. Plasma will then undergo a second centrifugation at 2500g for 15 minutes and be stored in cryogenic vials at -80ºC. Results will be expressed in pg/mL or ng/mL.
Time frame: Baseline, week 1 of intervention, week 12 of intervention and week 12 of detraining
Plasma biomarkers - Testosterone/cortisol ratio
Plasma ratio of testosterone/cortisol will be assessed by ELISA. Fasting venous blood samples will be collected by a qualified nurse from the antecubital vein into EDTA-treated vacutainers and centrifuged at 1500g for 10 minutes. Plasma will then undergo a second centrifugation at 2500g for 15 minutes and be stored in cryogenic vials at -80ºC. Results will be expressed in pg/mL or ng/mL.
Time frame: Baseline, week 1 of intervention, week 12 of intervention and week 12 of detraining
Biological age
Fasting venous blood samples will be collected by a qualified nurse from the antecubital vein and analysed at the Hospital Universitario Río Hortega laboratory. PhenoAge clock based on crhonological age and nine blood biomarkers: albumin, creatinine, glucose, C-reactive protein, lymphocyte %, mean corpuscular volume, red blood cell distribution width, alkaline phosphatase and white blood count). PhenoAge acceleration (years) will be computed as the residual from regression PhenoAge on chronological age.
Time frame: Baseline, week 1 of intervention, week 12 of intervention and week 12 of detraining
Intrinsic capacity - Cognition
Cognition will be measured by Mini-Mental State Examination (0-35 points).
Time frame: Baseline, week 1 of intervention (only verbal fluency), week 12 of intervention and week 12 of detraining
Intrinsic capacity - Cognition
Cognition will also be measured by Clock Drawing Test (0-10 points)
Time frame: Baseline, week 1 of intervention (only verbal fluency), week 12 of intervention and week 12 of detraining
Intrinsic capacity - Cognition
Cognition will also be measured verbal fluency (words/min).
Time frame: Baseline, week 1 of intervention (only verbal fluency), week 12 of intervention and week 12 of detraining
Intrinsic capacity - Locomotion
Locomotion will be assessed using the Short Physical Performance Battery (0-12 points).
Time frame: Baseline, week 12 of intervention and week 12 of detraining
Intrinsic capacity - Locomotion
Locomotion will be also assessed using the sit-to-stand muscle power (W) measured by PowerFrail app.
Time frame: Baseline, week 12 of intervention and week 12 of detraining
Intrinsic capacity - Vitality
Vitality will be measured by Mini-Nutritional Assessment (0-30 points).
Time frame: Baseline, week 12 of intervention and week 12 of detraining
Intrinsic capacity - Vitality
Vitality will also be measured by peak expiratory peak flow (L/min).
Time frame: Baseline, week 12 of intervention and week 12 of detraining
Intrinsic capacity - Vitality
Vitality will also be measured by handgrip strength (kg).
Time frame: Baseline, week 12 of intervention and week 12 of detraining
Intrinsic capacity - Psychological
Psychological domain will be assessed using the Cornell Scale for Depression in Dementia (0-38 points).
Time frame: Baseline, week 12 of intervention and week 12 of detraining
Intrinsic capacity - Psychological
Psychological domain will also be assessed using the Geriatric Depression Scale-10 (0-10 points).
Time frame: Baseline, week 12 of intervention and week 12 of detraining
Intrinsic capacity - Psychological
Psychological domain will also be assessed using the Neuropsychiatric inventory.
Time frame: Baseline, week 12 of intervention and week 12 of detraining
Intrinsic capacity - Sensory capacity
Sensory domain will be assessed by self-, clinician- or caregiver-reported vision and hearing problems
Time frame: Baseline, week 12 of intervention and week 12 of detraining
Quadriceps muscle thickness
Rectus femoris and vastus lateralis thickness (cm) will be measured with a real-time B-mode ultrasound (MyLab Gamma, Esaote, Genoa, Italy) and a linear transducer (SL 1543, 3-13 MHz; Esaote)
Time frame: Baseline, week 12 of intervention and week 12 of detraining
Functional outcomes - Functional capacity
Functional capacity will be assessed using the 6-Minute walking test (6MWT). Participants will walk along a 30-metre corridor marked every 10 metres to cover the maximum distance possible in six minutes. Total distance will be recorded (in meters). r.
Time frame: Baseline, week 12 of intervention and week 12 of detraining
Functional outcomes - Functional independence in basic activities of daily living
The Barthel Index assesses ten basic activities of daily living. The score ranges from 0 to 100 points, with higher scores indicating greater independence: total dependence (0-20), severe (21-60), moderate (61-90), mild dependence (91-99) and independence (100).
Time frame: Baseline, week 12 of intervention and week 12 of detraining
Functional outcomes - Heart rate recovery
Additionally to the distance, heart rate recovery (bpm) will be calculated as the difference between heart rate at the end of the test (6MWT) and one minute after
Time frame: Baseline, week 12 of intervention and week 12 of detraining
Functional outcomes - Functional independence in instrumental activities of daily living
The Lawton and Brody Scale evaluates eight instrumental activities of daily living. The score ranges from 0 to 8 points, with lower scores indicating greater dependence.
Time frame: Baseline, week 12 of intervention and week 12 of detraining
Clinical outcomes - Bioimpedance
The NUTRILAB bioimpedance device (AKERN Srl, Florence, Italy) will be used. This non-invasive method measures the body's resistance and reactance of the body to the passage of a low-intensity electric current and enables the determination of various body parameters. Bioimpedance provides accurate data on body fat percentage, muscle mass, total body water and other relevant indicators such as phase angle and Z-score. Users will be instructed to remove all metal-containing objects and remain in a supine position on a couch during the measurements, with the legs in 45° abduction, the shoulders in 30° abduction relative to the center of the body and the hands in pronation. After cleaning the skin with alcohol, two adhesive electrodes (Biatrodes Akern Srl, Florence, Italy) will be placed on the surface of the right hand and two on the right foot. The measurement results will be given in different unit measures depending on the specific variable assessed
Time frame: Baseline, week 12 of intervention and week 12 of detraining
Clinical outcomes - Risk of sarcopenia
Sarcopenia will be assessed following the European Working Group on Sarcopenia in Older People (EWGSOP2) algorithm.
Time frame: Baseline, week 12 of intervention and week 12 of detraining
Clinical outcomes - Comorbidities
Comorbidities will be recorded through the Charlson Comorbidity Index. Score is given in points, ith higher scores indicating greater comorbidity burden.
Time frame: Baseline, week 12 of intervention and week 12 of detraining
Pyschosocial outcomes - Caregiver burden
Caregiver burden will be assessed by the Zarit Burden Interview. It consists of 22 items on the caregiver's psychosocial, economic and emotional well-being. The score ranges from 0 to 88 points, with higher scores indicating greater caregiver burden.
Time frame: Baseline, week 12 of intervention and week 12 of detraining
Pyschosocial outcomes - Socio-familial situation
The Gijón Socio-Familial Assessment will be used. It evaluates five dimensions: personal situation, economic situation, housing, social relationships and support from the social network. The score ranges from 5 to 25 points, with higher scores indicating greater social risk (15 or more indicates a social problem).
Time frame: Baseline, week 12 of intervention and week 12 of detraining
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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European University Miguel de Cervantes