Combined Aerobic Exercise and Cognitive Training in Seniors at Increased Risk for Alzheimer's Disease

July 20, 2023 updated by: Xuanwu Hospital, Beijing

Combined Aerobic Exercise and Cognitive Training for Alzheimer's Disease Prevention in At-Risk Seniors Estimated by An Exosomal Synaptic Protein Model: Cognition and Exosomal Synaptic Proteins Effects

The study aims to investigate the effect of a long-term combined aerobic exercise and cognitive training program on cognitive function and blood exosomal synaptic protein levels in seniors at increased risk for Alzheimer's Disease.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Alzheimer's disease (AD) is the most common cause of dementia in people older than 65 years worldwide. The neuropathological changes of AD occur decades before the onset of cognitive impairment, suggesting that early identification and timely intervention may postpone the clinical progress. In addition to its characteristic amyloid β and tau pathology, AD is also marked by synaptic dysfunction. Abnormal synaptic protein levels, such as growth associated protein 43 (GAP43), neurogranin, synaptotagmins, and synaptosome associated protein 25 (SNAP25) have been observed in the brain tissue and cerebrospinal fluid (CSF). Blood neuro-exosomal synaptic proteins have emerged as promising predictors for AD and cognitive decline. Particularly, the investigators previously reported a combination of blood neuro-exosomal protein (GAP43, neurogranin, SNAP25, and synaptotagmin 1) can predict AD 5 to 7 years before the clinical onset.

Both physical exercise and cognitive training have been demonstrated to improve cognitive function in AD and to exert a protective effect against developing dementia in the normal aging population. Furthermore, cognitive stimulation is an established modulator of synaptic plasticity and physical exercise might regulate synapse functional and structural change. However, whether cognitive training and physical exercise can alter exosomal synaptic protein levels and the relationship of biomarker changes to cognitive function in those seniors at increased risk for AD remain unclear.

In this study, the investigators aim to

  1. assess the effects of a long-term combined aerobic exercise and cognitive training program on cognitive function and the predictive biomarkers (blood neuro-exosomal synaptic proteins: GAP43, neurogranin, SNAP25, and synaptotagmin 1) in seniors at increased risk of AD with abnormally decreased levels of the biomarkers.
  2. determine the relationship of biomarker changes with cognitive function in these people.
  3. confirm the predictive value of the blood neuro-exosomal synaptic proteins for AD in a longitudinal setting.

Study Type

Interventional

Enrollment (Estimated)

200

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

50 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Mandarin-speaking subjects.
  • Not clinically demented.
  • Meeting the cutoff values of MMSE and CDR.
  • With low levels of blood neuro-exosomal synaptic proteins (GAP43<1983pg/ml, synaptotagmin 1<431pg/ml, neurogranin<1433pg/ml, SNAP25<448pg/ml)

Exclusion criteria:

  • Had major neurologic diagnosis (e.g., Alzheimer's disease, Parkinson's disease, stroke, encephalitis, and epilepsy) or other condition that might impair cognition or confound assessments.
  • Had a history of psychotic episodes or had major depression (Hamilton Depression Rating Scale score > 24 points).
  • Had severe systemic diseases, such as tumors, cardiovascular or orthopedic disorders that can affect the ability to perform the proposed intervention tasks.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Combined aerobic exercise and cognitive training program
Behavioral: Combined aerobic exercise and cognitive training program
Participants will take part in a combined aerobic exercise and cognitive training program. The program will include moderate cycling exercise and cognitive game resolving at the same time. The tasks will be instructed and supervised by a fitness expert and a trained clinical neuropsychologist.
No Intervention: Standard health counseling at baseline

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in cognitive function over time as assessed by the Montreal Cognitive Assessment (MoCA)
Time Frame: baseline time, year 1, year 3, year 5, year 7
MoCA will be performed to evaluate the cognition of participants at the enrollment and year 1, year 3, year 5, year 7. The score ranges from 0 to 30, with higher values indicating better cognition.
baseline time, year 1, year 3, year 5, year 7
Change in cognitive function over time as assessed by Mini Mental State Examination (MMSE)
Time Frame: baseline time, year 1, year 3, year 5, year 7
MMSE will be performed to evaluate the cognition of participants at the enrollment and year 1, year 3, year 5, year 7. The score ranges from 0 to 30, with higher values indicating better cognition.
baseline time, year 1, year 3, year 5, year 7
Change in cognitive function over time as assessed by Clinical Dementia Rating (CDR)
Time Frame: baseline time, year 1, year 3, year 5, year 7
CDR will be performed to evaluate the cognition of participants at the enrollment and year 1, year 3, year 5, year 7. The score ranges from 0 to 18, with higher values indicating worse cognition.
baseline time, year 1, year 3, year 5, year 7
Change in cognitive function over time as assessed by Verbal Fluency Test
Time Frame: baseline time, year 1, year 3, year 5, year 7
Verbal Fluency Test will be performed to evaluate the semantic memory function of participants at the enrollment and year 1, year 3, year 5, year 7. Participants are asked to produce as many animals as possible within 1 minute. The score is the number of animals, with higher scores indicating better cognition.
baseline time, year 1, year 3, year 5, year 7
Change in cognitive function over time as assessed by Digit Span Test-Forward and Backward
Time Frame: baseline time, year 1, year 3, year 5, year 7
Digit Span Tests will be performed to evaluate the working memory of participants at the enrollment and year 1, year 3, year 5, year 7. The total scores are twelve for each test, with higher values indicating better cognition.
baseline time, year 1, year 3, year 5, year 7
Change in cognitive function over time as assessed by Trail-Making Test Parts A and B (TMT-A and TMT-B)
Time Frame: baseline time, year 1, year 3, year 5, year 7
TMT-A and TMT-B will be performed to evaluate the executive function of participants at the enrollment and year 1, year 3, year 5, year 7. Scoring is based on time taken to complete the test (e.g., 35 seconds yielding a score of 35), with lower scores indicating better cognition.
baseline time, year 1, year 3, year 5, year 7
Change in cognitive function over time as assessed by Boston Naming Test (BNT)
Time Frame: baseline time, year 1, year 3, year 5, year 7
BNT will be performed to evaluate the language function of participants at the enrollment and year 1, year 3, year 5, year 7. The score ranges from 0 to 30, with higher values indicating better cognition.
baseline time, year 1, year 3, year 5, year 7
Change in cognitive function over time as assessed by the Rey-Osterrieth Complex Figure Test (ROCF)
Time Frame: baseline time, year 1, year 3, year 5, year 7
ROCF will be performed to evaluate the visuospatial function and other cognition domains of participants at the enrollment and year 1, year 3, year 5, year 7. Participants are asked to produce a complicated line drawing, with higher scores indicating better cognition.
baseline time, year 1, year 3, year 5, year 7
Change in cognitive function over time as assessed by California Verbal Learning Test (CVLT)
Time Frame: baseline time, year 1, year 3, year 5, year 7
CVLT will be performed to evaluate the memory function of participants at the enrollment and year 1, year 3, year 5, year 7. Participants are asked to finish immediate recall, delayed recall, and delayed recognition tasks in the test, with higher scores indicating better cognition.
baseline time, year 1, year 3, year 5, year 7

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The area under curve of the blood neuro-exosomal synaptic proteins (GAP43, neurogranin, SNAP25, and synaptotagmin1) for the accurate diagnosis of AD
Time Frame: up to 7 years
The area under curve is used to show the ability of the blood neuro-exosomal synaptic proteins (GAP43, neurogranin, SNAP25, and synaptotagmin1) to diagnose AD. The value of area under curve is higher, then the ability of the blood neuro-exosomal synaptic proteins to diagnose AD is stronger.
up to 7 years
Changes in concentrations of blood neuro-exosomal GAP43 over time
Time Frame: baseline time, year 1, year 3, year 5, year 7
Concentrations of blood neuro-exosomal GAP43 will be evaluated at the enrollment and year 1, year 3, year 5, year 7, and measured in pg/ml.
baseline time, year 1, year 3, year 5, year 7
Changes in concentrations of blood neuro-exosomal neurogranin over time
Time Frame: baseline time, year 1, year 3, year 5, year 7
Concentrations of blood neuro-exosomal neurogranin will be evaluated at the enrollment and year 1, year 3, year 5, year 7, and measured in pg/ml.
baseline time, year 1, year 3, year 5, year 7
Changes in concentrations of blood neuro-exosomal SNAP25 over time
Time Frame: baseline time, year 1, year 3, year 5, year 7
Concentrations of blood neuro-exosomal SNAP25 1 will be evaluated at the enrollment and year 1, year 3, year 5, year 7, and measured in pg/ml.
baseline time, year 1, year 3, year 5, year 7
Changes in concentrations of blood neuro-exosomal synaptotagmin1 over time
Time Frame: baseline time, year 1, year 3, year 5, year 7
Concentrations of blood neuro-exosomal synaptotagmin1 will be evaluated at the enrollment and year 1, year 3, year 5, year 7, and measured in pg/ml.
baseline time, year 1, year 3, year 5, year 7

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Xuanwu Hospital, Beijing

Investigators

  • Principal Investigator: Longfei Jia, MD,PhD, Xuanwu Hospital, Beijing

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

December 1, 2024

Primary Completion (Estimated)

December 1, 2034

Study Completion (Estimated)

December 1, 2034

Study Registration Dates

First Submitted

November 22, 2021

First Submitted That Met QC Criteria

December 6, 2021

First Posted (Actual)

December 20, 2021

Study Record Updates

Last Update Posted (Estimated)

July 24, 2023

Last Update Submitted That Met QC Criteria

July 20, 2023

Last Verified

November 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ICND20210920

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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