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Exercise in Alzheimer's Disease: Functional Biomarkers (AD-GUT-EX)

2026年10月30日 更新者：European University Miguel de Cervantes

Physical Exercise in Alzheimer's Disease: Impact on Functional Biomarkers and the Muscle-Gut-Brain Axis

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.

調査の概要

状態

まだ募集していません

条件

介入・治療

詳細な説明

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.

研究の種類

介入

入学 (推定)

48

段階

  • 適用できない

連絡先と場所

このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。

研究連絡先

  • 名前：Alejandro Santos-Lozano, PhD
  • 電話番号：22292 +34983001000
  • メール：asantos@uemc.es

研究連絡先のバックアップ

  • 名前：Fabrzio Evangelista, Nurse

研究場所

  • スペイン
    • Valladolid
      • Valladolid、Valladolid、スペイン、47012
        • Miguel de Cervantes European University
        • 副調査官：
          • María Merino País, MSc, PhD student
        • 副調査官：
          • Susana López Ortiz, PhD
        • 副調査官：
          • Celia García Chico, PhD
        • コンタクト：
          • Francisco Javier Gutiérrez Pecharrómán
          • 電話番号：22293 +34 983 001 000
          • メール：dit@uemc.es
        • 主任研究者：
          • Alejandro Santos Lozano, PhD
        • 主任研究者：
          • Fabrizio Evangelista, MSc
        • 副調査官：
          • Alba Canteli Diez, MSc, PhD student
        • 副調査官：
          • Virginia Carbajosa Rodríguez, PhD
        • 副調査官：
          • Sara del Amo Ramos, MD
        • 副調査官：
          • Daniel Arévalo Sillero, MSc
        • 副調査官：
          • Mónica Álvarez Muñoz, MD
        • 副調査官：
          • Javier Guitiérrez Redondo
        • 副調査官：
          • Francisco Javier Iruzubieta Barragan, PhD

参加基準

研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。

適格基準

就学可能な年齢

60年歳以上 (大人、高齢者)

健康ボランティアの受け入れ

はい

受講資格のある性別

全て

説明

Inclusion Criteria - participants with Alzheimer's Disease

  • Age ≥ 60 years
  • Medical diagnosis of mild or moderate Alzheimer's disease based on clinical criteria and plasma biomarkers.
  • Able to perform physical activity according to medical assessment
  • Written informed consent from the participant or, when capacity is insufficient, from the legal representative

Inclusion Criteria - cognitively healthy reference group

  • Age ≥ 60 years
  • No medical diagnosis of Alzheimer's disease or cognitive impairment according to clinical criteria
  • Preserved functional autonomy
  • Able to perform physical activity according to medical assessment
  • Written informed consent

Exclusion Criteria:

  • Major surgery in the previous 3 months
  • Total functional dependence
  • Uncontrolled neuromuscular disease or severe heart disease
  • Antibiotic, probiotic or corticosteroid treatment in the 4 weeks before biological sample collection

研究計画

このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。

研究はどのように設計されていますか？

デザインの詳細

  • 主な目的：ヘルスサービス研究
  • 割り当て：ランダム化
  • 介入モデル：並列代入
  • マスキング：独身

武器と介入

参加者グループ / アーム
介入・治療
実験的：Alzheimer's disease - High load

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.
他の：High 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.
実験的：Alzheimer's disease - Moderate 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.
他の：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 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.
介入なし：Alzheimer's disease - Usual care

Participants with mild-to-moderate AD continue their usual care only (cognitive therapy, music therapy or other routine therapies).
他の：Healthy reference group

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.
他の：Healthy adults - High load

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.

他の：Healthy adults - Moderate load

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.

この研究は何を測定していますか？

主要な結果の測定

結果測定
メジャーの説明
時間枠
Gut microbiome
時間枠：Baseline, week 12 of intervention

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.
Baseline, week 12 of intervention
Inflammation indices - Systemic Inflammation Response Index
時間枠：Baseline, week 1 of intervention, week 12 of intervention and week 12 of detraining

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.
Baseline, week 1 of intervention, week 12 of intervention and week 12 of detraining
Plasma biomarkers - Brain-derived neurotrophic factor
時間枠：Baseline, week 1 of intervention, week 12 of intervention and week 12 of detraining

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.
Baseline, week 1 of intervention, week 12 of intervention and week 12 of detraining
Inflammation indices - Aggregate Index of Systemic Inflammation
時間枠：Baseline, week 1 of intervention, week 12 of intervention and week 12 of detraining

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.
Baseline, week 1 of intervention, week 12 of intervention and week 12 of detraining
Plasma biomarkers - p-tau217
時間枠：Baseline, week 1 of intervention, week 12 of intervention and week 12 of detraining

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.
Baseline, week 1 of intervention, week 12 of intervention and week 12 of detraining
Plasma biomarkers - Klotho
時間枠：Baseline, week 1 of intervention, week 12 of intervention and week 12 of detraining

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.
Baseline, week 1 of intervention, week 12 of intervention and week 12 of detraining
Plasma biomarkers - Testosterone/cortisol ratio
時間枠：Baseline, week 1 of intervention, week 12 of intervention and week 12 of detraining

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.
Baseline, week 1 of intervention, week 12 of intervention and week 12 of detraining
Biological age
時間枠：Baseline, week 1 of intervention, week 12 of intervention and week 12 of detraining

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.
Baseline, week 1 of intervention, week 12 of intervention and week 12 of detraining

二次結果の測定

結果測定
メジャーの説明
時間枠
Intrinsic capacity - Cognition
時間枠：Baseline, week 1 of intervention (only verbal fluency), week 12 of intervention and week 12 of detraining

Cognition will be measured by Mini-Mental State Examination (0-35 points).
Baseline, week 1 of intervention (only verbal fluency), week 12 of intervention and week 12 of detraining
Intrinsic capacity - Cognition
時間枠：Baseline, week 1 of intervention (only verbal fluency), week 12 of intervention and week 12 of detraining

Cognition will also be measured by Clock Drawing Test (0-10 points)
Baseline, week 1 of intervention (only verbal fluency), week 12 of intervention and week 12 of detraining
Intrinsic capacity - Cognition
時間枠：Baseline, week 1 of intervention (only verbal fluency), week 12 of intervention and week 12 of detraining

Cognition will also be measured verbal fluency (words/min).
Baseline, week 1 of intervention (only verbal fluency), week 12 of intervention and week 12 of detraining
Intrinsic capacity - Locomotion
時間枠：Baseline, week 12 of intervention and week 12 of detraining

Locomotion will be assessed using the Short Physical Performance Battery (0-12 points).
Baseline, week 12 of intervention and week 12 of detraining
Intrinsic capacity - Locomotion
時間枠：Baseline, week 12 of intervention and week 12 of detraining

Locomotion will be also assessed using the sit-to-stand muscle power (W) measured by PowerFrail app.
Baseline, week 12 of intervention and week 12 of detraining
Intrinsic capacity - Vitality
時間枠：Baseline, week 12 of intervention and week 12 of detraining

Vitality will be measured by Mini-Nutritional Assessment (0-30 points).
Baseline, week 12 of intervention and week 12 of detraining
Intrinsic capacity - Vitality
時間枠：Baseline, week 12 of intervention and week 12 of detraining

Vitality will also be measured by peak expiratory peak flow (L/min).
Baseline, week 12 of intervention and week 12 of detraining
Intrinsic capacity - Vitality
時間枠：Baseline, week 12 of intervention and week 12 of detraining

Vitality will also be measured by handgrip strength (kg).
Baseline, week 12 of intervention and week 12 of detraining
Intrinsic capacity - Psychological
時間枠：Baseline, week 12 of intervention and week 12 of detraining

Psychological domain will be assessed using the Cornell Scale for Depression in Dementia (0-38 points).
Baseline, week 12 of intervention and week 12 of detraining
Intrinsic capacity - Psychological
時間枠：Baseline, week 12 of intervention and week 12 of detraining

Psychological domain will also be assessed using the Geriatric Depression Scale-10 (0-10 points).
Baseline, week 12 of intervention and week 12 of detraining
Intrinsic capacity - Psychological
時間枠：Baseline, week 12 of intervention and week 12 of detraining

Psychological domain will also be assessed using the Neuropsychiatric inventory.
Baseline, week 12 of intervention and week 12 of detraining
Intrinsic capacity - Sensory capacity
時間枠：Baseline, week 12 of intervention and week 12 of detraining

Sensory domain will be assessed by self-, clinician- or caregiver-reported vision and hearing problems
Baseline, week 12 of intervention and week 12 of detraining
Quadriceps muscle thickness
時間枠：Baseline, week 12 of intervention and week 12 of detraining

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)
Baseline, week 12 of intervention and week 12 of detraining
Functional outcomes - Functional capacity
時間枠：Baseline, week 12 of intervention and week 12 of detraining

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.
Baseline, week 12 of intervention and week 12 of detraining
Functional outcomes - Functional independence in basic activities of daily living
時間枠：Baseline, week 12 of intervention and week 12 of detraining

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).
Baseline, week 12 of intervention and week 12 of detraining
Functional outcomes - Heart rate recovery
時間枠：Baseline, week 12 of intervention and week 12 of detraining

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
Baseline, week 12 of intervention and week 12 of detraining
Functional outcomes - Functional independence in instrumental activities of daily living
時間枠：Baseline, week 12 of intervention and week 12 of detraining

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.
Baseline, week 12 of intervention and week 12 of detraining
Clinical outcomes - Bioimpedance
時間枠：Baseline, week 12 of intervention and week 12 of detraining

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
Baseline, week 12 of intervention and week 12 of detraining
Clinical outcomes - Risk of sarcopenia
時間枠：Baseline, week 12 of intervention and week 12 of detraining

Sarcopenia will be assessed following the European Working Group on Sarcopenia in Older People (EWGSOP2) algorithm.
Baseline, week 12 of intervention and week 12 of detraining
Clinical outcomes - Comorbidities
時間枠：Baseline, week 12 of intervention and week 12 of detraining

Comorbidities will be recorded through the Charlson Comorbidity Index. Score is given in points, ith higher scores indicating greater comorbidity burden.
Baseline, week 12 of intervention and week 12 of detraining
Pyschosocial outcomes - Caregiver burden
時間枠：Baseline, week 12 of intervention and week 12 of detraining

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.
Baseline, week 12 of intervention and week 12 of detraining
Pyschosocial outcomes - Socio-familial situation
時間枠：Baseline, week 12 of intervention and week 12 of detraining

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).
Baseline, week 12 of intervention and week 12 of detraining

協力者と研究者

ここでは、この調査に関係する人々や組織を見つけることができます。

スポンサー

European University Miguel de Cervantes

協力者

Hospital Rio Hortega

研究記録日

これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。

主要日程の研究

研究開始 (推定)

2026年11月10日

一次修了 (推定)

2027年10月31日

研究の完了 (推定)

2027年12月1日

試験登録日

最初に提出

2026年10月26日

QC基準を満たした最初の提出物

2026年10月30日

最初の投稿 (実際)

2026年11月5日

学習記録の更新

投稿された最後の更新 (実際)

2026年11月5日

QC基準を満たした最後の更新が送信されました

2026年10月30日

最終確認日

2026年10月1日

詳しくは

本研究に関する用語

キーワード

追加の関連 MeSH 用語

その他の研究ID番号

  • PI-DOC013-ADD-GUT-EXERCISE

医薬品およびデバイス情報、研究文書

米国FDA規制医薬品の研究

いいえ

米国FDA規制機器製品の研究

いいえ

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