Effects of Combined Aerobic and Cognitive Training in a Simultaneous or Sequential Paradigm on Cognition and Brain Functional Activity in Patients with AMCI

Not Applicable

Active, not recruiting

• Conditions: Mild Cognitive Impairment (MCI); AMCI - Amnestic Mild Cognitive Impairment; Neurodegenerative Dementia; Neurodegenerative Disease

• Registration Number: NCT06755164
• Lead Sponsor: IRCCS San Raffaele

Brief Summary

Mild Cognitive Impairment (MCI) is a condition in which patients show an objective evidence of impairment in one or more cognitive domains but a spared independence in daily functional abilities. The cognitive domain which results to be the most impaired defines the clinical subtype. Specifically, the amnestic subtype of MCI (aMCI), which is the most frequent, is characterised by deficits in episodic memory and visuospatial abilities. Current literature reports that prompt and focused rehabilitation provided early in the disease course might slow down the development of the neurodegenerative condition. The coupling between cognitive and aerobic trainings is the most incisive non-pharmacological treatment, and its effects have been demonstrated to have an impact on global cognitive functions, quality of life, aerobic capacity, and mood in the elderly with aMCI. However, the best modality for coupling aerobic and cognitive trainings (i.e., whether sequential-SEQ: aerobic training followed by cognitive training; or simultaneous-SIM: cognitive training during aerobic training) is still unknown. The aim of the present study is to determine which modality, among SEQ or SIM, is the most incisive training in patients with aMCI. Using a Randomized Controlled design, the effect of this combined aerobic-cognitive non-pharmachological training in both modalities will be evaluated on cognitive changes assessed with standard and computerized neuropsychological batteries and in functional activity during a task-based functional Magnetic Resonance Imaging (fMRI) scan.

Detailed Description

This study will be the first one aimed at investigating the effects of a combined aerobic and cognitive training in the two different paradigms (SIM and SEQ) on cognitive functioning and brain functional MRI activity in patients with aMCI. Previous studies on aMCI patients reported that the combination of cognitive and aerobic training is more effective than the single treatments alone on both clinical and MRI outcome measures. Specifically, with the proposed training we expect to obtain ameliorative effects in terms of episodic memory, visuospatial abilities, cerebral activity and aerobic capacities, with a consequent benefit on quality of life and mood in both experimental groups; in addition, we also expect a reduction of IL-6 and TNF-alpha expression levels, and an enhancement of the BDNF.

The combined aerobic-cognitive training (in SIM and SEQ modalities) will have a duration of 3 months, with 24 sessions scheduled twice a week for 70 minutes each.

The first session will last 10 minutes more compared to the others in order to provide participants with all information concerning the cognitive task that they will perform during (in SIM condition) or after the aerobic training (in SEQ condition).

Aerobic and cognitive exercises will be the same for both groups (SIM and SEQ) and will be characterized as follows:

* Aerobic training: 30 minutes of cyclette at 40-59% heart rate reserve (HRR) or 64-76% maximum heart rate (corresponding at Rating of Perceived Exertion by Borg -BORG RPE= 12-13 -moderate intensity-).16 The cardiac frequency will be monitored by pulse oxymeter.

* Cognitive training: the entire training will last for 30 minutes and will consist of two cycles of a memory task (lasting 10 minutes) and a visuospatial task (5 minutes).

For the SIM condition, patient will perform the cognitive training sited on the cyclette using an adapted computer screen and a joystick.

For the SEQ condition, patient will perform the cognitive training sited on a desk using a computer and a joystick.

The aerobic training will be performed on a cyclette. For the cognitive training, the cognitive exercises will train two cognitive domain 1) memory and 2) visuospatial function. 1) During the mnemonic exercises, the patients will be asked to observe a screen on which different stimuli (objects) will be presented and to remember all of them. Then the subjects will be asked to recall the most of the observed objects. The number of stimuli (objects) will progressively increase in order to progressively improving the difficulty of the mnemonic training. 2) The visuospatial task will consist on the navigation in a labyrinth projected onto a screen. The subjects will have a mouse/joystick with which they will move through the labyrinth in order to find the shortest way to exit.

Study Timeline

• Study Start: 2019-04-05
• Primary Completion: 2024-01-16
• Status Verified: 2024-12
• Study First Submitted: 2024-12-13
• Study First Submitted QC: 2024-12-24
• Study First Posted: 2025-01-01
• Last Update Submitted: 2025-01-08
• Last Update Posted: 2025-01-10
• Study Completion: 2025-02-28

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 55

Inclusion Criteria

• a diagnosis of amnesic mild cognitive impairment according to the current diagnostic criteria;
• age>60 years;
• stable acetylcholinesterase inhibitors and/or memantine at the time of enrolment for at least one month;
• subscription of the consent for personal data treatment and patients' informed consent for participation in the present study.

Exclusion Criteria

• patients with a history of other systemic, neurologic, psychiatric diseases, head injury, cardiovascular events, and cerebrovascular alterations visible at an MRI scan;
• patients with a family history of neurodegenerative disorders;
• patients with a history of alcohol and/or psychotropic drugs abuse;
• patients who are used to do regular physical and/or cognitive activity;
• contraindication to perform MRI scan (cardiac pace-maker or other types of cardiac catheters, splinters or metallic shards, metallic prosthesis not compatible with magnetic field generated by MRI, claustrophobia, pregnancy, breastfeeding).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Episodic memory improvement	Baseline, month 3, month 9	The primary aim of the study is to investigate episodic memory improvement (investigated with changes in the Alzheimer's Disease Assessment Scale (ADAS-cog scale), both in short- (sooner after training) and in long-term (6 months after training). ADAS-Cog scale is a useful tool which is widely employed to assess global cognitive functioning in patients with several neurodegenerative conditions including MCI. Range score is from 0 to 70. Lower scores indicate better performance.

Secondary Outcome Measures

Name	Time	Method
Changes in submaximal aerobic/functional walking capacity	Baseline, month 3, month 9	The 6-minute walking test (6MWT) measures the distance a subject walks in 6 minutes and is used to assess changes in performance capacity
Functional MRI changes	Baseline, month 3	Modifications in cerebral functional activity, measured through BOLD signal, soon after training using a task-based fMRI approach.
Mood changes	Baseline, month 3, month 9	Changes in mood, as measured by the Beck Depression Inventory (BDI), following treatment at both short- and long-term follow-up. BDI is a 21-item, self-administered questionnaire designed to assess the severity of respondents' depression during the weeks prior to completing the questionnaire.
Quality of life changes	Baseline, month 3, month 9	Modifications in quality of life as measured by the 12-item Short Form Survey (SF-12) after treatment at the short- and long-term follow up. The SF-12 is a 12-questions instrument for assessing self-reported health-related quality of life.
Inflammatory cytokines changes	Baseline, month 3, month 9	To observe a reduction in inflammatory cytokines expression levels, specifically in interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-alpha) levels, measured at the short- and long-term follow up. This biochemical effects will have a positive effect on brain-derived neurotrophic factor (BDNF).
Correlation between BOLD activity during task-based fMRI and after-treatment changes in cognition	month 3, month 9	Correlation between fMRI BOLD activity and changes in cognitive function in both conditions (SIM and SEQ) after treatment at short and at long-term follow up.
Correlation between after-treatment changes in BOLD fMRI activity and cognition	Month 3	Correlation between changes in BOLD activity and cognitive functioning in both conditions (SIM and SEQ) after treatment at short and at long-term follow up.
Correlation between biological factors and after-treatment changes in cognition	Baseline, month 3, month 9	Correlation between changes in cognitive functioning and biological factors in both conditions (SIM and SEQ) after treatment at short and at long-term follow up.
Differences in patterns of brain activation between HC and patients	Baseline	To study brain activation differences between patients and healthy subjects by comparing fMRI BOLD activity.
Cognitive differences between HC and patients	Baseline	Baseline cognitive differences between patients and healthy subjects using the Alzheimer's Disease Assessment Scale - Cognitive subscale (ADAS-Cog scale).
Biological differences between HC and patients	Baseline	Biological differences in BDNF, IL-6, and TNF-alpha levels between patients and healthy controls.

Trial Locations

Locations (1)

IRCCS San Raffaele; 🇮🇹 Milan, MI, Italy