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.
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
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
DOUBLE
Enrollment
20
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 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.
University of Granada
Granada, Andalusia, Spain
Mind, Brain, and Behaviour Research Centre (CIMCYC, Centro de Investigación Mente, Cerebro y Comportamiento)
Granada, Spain
Change in Cerebral Blood Flow (CBF)
Specific acquisition parameters for Pseudo continuous Arterial Spin Labeling (pCASL) sequence are used to determinate global and regional CBF in resting condition. Structural T1 sequence (only pre-condition) is used to coregisted the pCASL and delineate regions of interest for CBF. Time-of-flight angiography (TOF) (before pCASL pre-condition and before first pCASL post-condition) sequence is used to identify the carotid arteries. The unit of measurement of the CBF is expressed as milliliters per 100 grams of brain tissue per minute (mL/100 g/min).
Time frame: 30 minutes before the experimental condition; and 20 minutes, 27 minutes and 34 minutes minutes after the experimental condition
Change in Alzheimer disease blood-based biomarkers (Aβ42/40 ratio)
The following biomarkers will be assessed: Amyloid-beta 42 (Aβ42), Amyloid-beta 40 (Aβ40). Aβ42 and Aβ40 will be combined to report Aβ42/40 ratio. Unit of measurement: Aβ42/40 is a ratio (no units) and represents the relative concentration of Aβ42 to Aβ40.
Time frame: 5 minutes before the experimental condition; and 0 minutes, 50 minutes and 70 minutes after the experimental condition
Change in Alzheimer disease blood-based biomarkers (p-tau217, p-tau181, NfL and GFAP)
The following biomarkers will be assessed: phosphorylated tau protein at positions 217 and 181 (p-tau217, p-tau181), Glial Fibrillary Acidic Protein (GFAP) and Neurofilament Light Chain (NfL). Unit of measurement: p-tau217, p-tau181, NfL and GFAP are commonly measured in picograms per milliliter (pg/mL).
Time frame: 5 minutes before the experimental condition; and 0 minutes, 50 minutes and 70 minutes after the experimental condition
Change in growth factors (BDNF)
Brain-Derived Neurotrophic Factor (BDNF) will be measured. Unit of measurement: BDNF is commonly measured in picograms per milliliter (pg/mL).
Time frame: 5 minutes before the experimental condition; and 0 minutes, 50 minutes and 70 minutes after the experimental condition
Change in growth factors (IGF-1)
Insulin-Like Growth Factor 1 (IGF-1) will be measured. Unit of measurement: IGF-1 is commonly measured in nanograms per milliliter (ng/mL).
Time frame: 5 minutes before the experimental condition; and 0 minutes, 50 minutes and 70 minutes after the experimental condition
Change in episodic memory
Episodic memory will be assessed using the Picture Sequence Memory Test from the Cognitive NIH Toolbox. The Cognitive NIH Toolbox is a computer-based battery which is available in Spanish. The Picture Sequence Memory Test measures episodic memory by deriving the participant's score from the cumulative number of adjacent pairs of pictures remembered correctly over two learning trials. The variable used for the for the PSMT is the theta score: The number of adjacent pairs placed correctly for each of trials 1 and 2 is converted to a theta score. This is a representation of the given participant estimated ability in the task.
Time frame: 15 minutes before the experimental condition; and 60 minutes after the experimental condition
Change in inhibition/attention
The Flanker task measures inhibitory control and attention by using the inverse efficiency score of incongruent trials. The inverse efficiency score is calculated as reaction time/accuracy (RT/ACC).
Time frame: 15 minutes before the experimental condition; and 60 minutes after the experimental condition
Mood status
Mood status will be evaluated using the validated scale Profile of Mood States (POMS). The POMS scale is a psychological assessment tool used to measure and evaluate a person's mood states. It consists of a questionnaire with a list of 15 adjectives or mood descriptors, where individuals rate how they have been feeling on a scale typically ranging from "Not at all" to "Extremely". We use an abbreviated version of the scale with 15 ítems. The ítems are divided into 5 dimensions: depression, vigour, anger, tension and fatigue. The final score is: (\[depression\]+\[anger\]+\[tension\]+\[fatigue\]) - \[vigour\].
Time frame: POMS will be measured 60 minutes before the experimental condition; and 70 minutes after the experimental condition
Feeling scale
Emotional response will be evaluated using the feeling scale (FS). The FS is an 11-point scale ranging from -5 (very bad) to +5 (very good) used to measure an individual's emotional feeling in terms of pleasure or displeasure at a specific moment.
Time frame: Feeling scale will be measured 1 minute before the experimental condition; and 1 minute after the experimental condition
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.