Understanding Cerebral Blood Flow Dynamics for Alzheimer's Disease Prevention Through Exercise

NCT ID: NCT06584656

Last Updated: 2025-03-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-09-25
• Study Completion Date: 2025-01-02

Brief Summary

Dementia is one of the leading causes of disability worldwide. Underlying biological mechanisms are crucial in preclinical stages of Alzheimer's disease (AD). Alterations in cerebral blood flow (CBF) and their relationship with AD blood-based biomarkers may be fundamental at early stages of the pathology. Physical exercise is a trigger to modify these biological mechanisms. Therefore, flADex aims to examine the acute effects of different types of exercise (resistance vs. aerobic vs. control) on CBF, AD blood-based biomarkers, and its cognitive implications in older adults. The hypothesis is that acute resistance or aerobic exercise will fluctuate levels of blood-based biomarkers, and will exert acute CBF changes combined with cognitive implications.

Detailed Description

The aging population is at an increasing risk of developing Alzheimer's Disease (AD), which is characterized by cognitive decline and memory loss. Current pharmacological treatments have targeted amyloid-beta (Aβ) and tau protein, and have largely failed to halt or reverse the progression of AD. This has led to a growing interest on examining additional underlying mechanisms responsible for the initiation of AD pathology in this preclinical stage, such as cerebral blood flow (CBF) alterations or peripheral levels of AD blood-based biomarkers. Parallelly, exercise might act as a trigger for these potential underlying mechanisms of AD in older adults. Thus, this study seeks to explore the acute effects of different type of exercise on CBF, blood-based biomarkers, and its cognitive implications in older adults.

FlADex is a counterbalanced crossover trial that will include 20 adults aged 68 to 83 with non-pathological brain amyloid status (<12 centiloid) and APOE e4 noncarriers. Each participant will be included in all study conditions in a randomized order: (i) moderate aerobic exercise (between 60-70 of the Maximal Heart Rate (HRmax); (ii); resistance exercise (4-6 Moderate intensity of Rate of Perceived Exertion) and (iii) control resting condition. Each condition, lasting 30 minutes, will be performed once. CBF will be assessed by magnetic resonance imaging using pseudo-continuous arterial spin labeling at pre-condition and at 3 consecutive times post-condition (at 20', 27' and 34' min). Blood-based biomarkers (Aβ42, Aβ40, p-tau217, p-tau181, GFAP, NfL, BDNF, IGF-1) will be measured pre-condition and post-condition (at 0', 50', 70' min). Cognitive outcomes (Flanker Test and Picture Sequence Memory Test) and mood status (feeling scale and POMS questionnaire) will be measured pre and post condition.

FlADex trial will shed light on the acute effects of different types of exercises on CBF and AD blood-based biomarkers before beta-amyloid accumulation. We expect that aerobic and resistance exercise will have different effects on CBF dynamics and AD blood biomarker levels over time in older adults

Conditions

Healthy Aging; Cognitive Function 1, Social; Cerebrovascular Circulation; Blood Flow

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

Aerobic exercise group

-Aerobic group. 30 min at 60-70% of the Maximal Heart Rate, moderate intensity on cycle.

Group Type: EXPERIMENTAL

Aerobic exercise condition

Intervention Type: BEHAVIORAL

Aerobic session will last 30 min. The average intensity of the aerobic sessions will be 60-70% of the Maximal Heart Rate. Therefore, participant will perform a continuous moderate intensity aerobic bout of exercise on a cycle ergometer.

Resistance exercise group

30 min at 4-6 RPE (OMNI-Resistance Exercise Scale of Perceived Exertion), 3 sets of 8 exercise/set, 40 sec/exercise. Moderate intensity using elastic bands and body weight.

Group Type: EXPERIMENTAL

Resistance exercise condition

Intervention Type: BEHAVIORAL

Resistance exercise will last 30 min at 4-6 RPE (OMNI-Resistance Exercise Scale of Perceived Exertion from 0-10). The bout of resistance exercise will include a combination of upper and lower body exercises using elastic bands and the participants' body weight as the primary resistance. Eight different exercises will be performed per set, with 40 seconds per exercise, for a total of 3 sets. The exercises are based on basic movement patterns and include: glute bridge, front plank, standing face pull, incline push-up, squat, pallof press, walking lunge and seated shoulder press.

Control

30 min seated watching a neutral documentary without cognitive engagement

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Aerobic exercise condition

Aerobic session will last 30 min. The average intensity of the aerobic sessions will be 60-70% of the Maximal Heart Rate. Therefore, participant will perform a continuous moderate intensity aerobic bout of exercise on a cycle ergometer.

Intervention Type: BEHAVIORAL

Resistance exercise condition

Resistance exercise will last 30 min at 4-6 RPE (OMNI-Resistance Exercise Scale of Perceived Exertion from 0-10). The bout of resistance exercise will include a combination of upper and lower body exercises using elastic bands and the participants' body weight as the primary resistance. Eight different exercises will be performed per set, with 40 seconds per exercise, for a total of 3 sets. The exercises are based on basic movement patterns and include: glute bridge, front plank, standing face pull, incline push-up, squat, pallof press, walking lunge and seated shoulder press.

Intervention Type: BEHAVIORAL

Eligibility Criteria

Inclusion Criteria

• Older adults
• Aged 68-83 years
• Non-pathological cerebral beta-amyloid status (based on Centiloid cut-point <12 measured by PET-CT)
• APOEe4 negative status
• Willingness to participate in exercise interventions

Exclusion Criteria

• Pathological diagnosis related to physical or mental condition
• No living in community settings during the study
• MRI incompatibility
• Ambulatory with pain or regular use of an assisted walking device
• Severe cardiovascular or respiratory conditions
• Participation in another clinical trial within the last 30 days

• Minimum Eligible Age: 68 Years
• Maximum Eligible Age: 83 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University Hospital Virgen de las Nieves

OTHER

Sponsor Role: collaborator

Instituto Mixto Universitario Deporte y Salud (iMUDS)

UNKNOWN

Sponsor Role: collaborator

Centro de Investigación Mente, Cerebro y Comportamiento

UNKNOWN

Sponsor Role: collaborator

Universidad de Granada

OTHER

Sponsor Role: lead

Responsible Party

Irene Esteban-Cornejo

Ramon y Cajal Assistant Professor, PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Irene Esteban-Cornejo, PhD

Role: PRINCIPAL_INVESTIGATOR

Department of Physical Education and Sports, Faculty of Sport Sciences, University of Granada, Spain.

Locations

University of Granada

Granada, Andalusia, Spain

Mind, Brain, and Behaviour Research Centre (CIMCYC, Centro de Investigación Mente, Cerebro y Comportamiento)

Granada, , Spain

Countries

Spain

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://github.com/fladexprojectugr

Detailed information about the protocols, methodology , data analysis, and code used in this project will be upload to the GitHub repository: FLADEX Project GitHub Repository.

Other Identifiers

PID2022-137399OB-I0

Identifier Type: -

Identifier Source: org_study_id