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

NCT05163626 | Not Yet Recruiting DMC

• 1 other identifier: ICND20210920
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Alzheimer Disease

Keywords

Alzheimer's disease; aerobic exercise; exosome; synaptic protein; biomarker; prevention; cognitive training

Outcome Measures

Primary Outcomes (9)

• Change in cognitive function over time as assessed by the Montreal Cognitive Assessment (MoCA)

  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)

  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)

  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

  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

  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)

  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)

  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)

  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)

  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 Outcomes (5)

• Changes in concentrations of blood neuro-exosomal GAP43 over time

  baseline time, year 1, year 3, year 5, year 7

• Changes in concentrations of blood neuro-exosomal neurogranin over time

  baseline time, year 1, year 3, year 5, year 7

• Changes in concentrations of blood neuro-exosomal SNAP25 over time

  baseline time, year 1, year 3, year 5, year 7

• Changes in concentrations of blood neuro-exosomal synaptotagmin1 over time

  baseline time, year 1, year 3, year 5, year 7

• The area under curve of the blood neuro-exosomal synaptic proteins (GAP43, neurogranin, SNAP25, and synaptotagmin1) for the accurate diagnosis of AD

  up to 7 years

Study Arms (2)

Combined aerobic exercise and cognitive training program

EXPERIMENTAL

Behavioral: Combined aerobic exercise and cognitive training program

Standard health counseling at baseline

NO INTERVENTION

Interventions

Combined aerobic exercise and cognitive training program BEHAVIORAL

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.

Combined aerobic exercise and cognitive training program

Eligibility Criteria

• Age: 50 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Xuanwu Hospital, Beijing: lead

Study Sites (1)

Xuanwu Hospital

Beijing, China

Location

Related Publications (7)

• Jia L, Zhu M, Kong C, Pang Y, Zhang H, Qiu Q, Wei C, Tang Y, Wang Q, Li Y, Li T, Li F, Wang Q, Li Y, Wei Y, Jia J. Blood neuro-exosomal synaptic proteins predict Alzheimer's disease at the asymptomatic stage. Alzheimers Dement. 2021 Jan;17(1):49-60. doi: 10.1002/alz.12166. Epub 2020 Aug 10.

  PMID: 32776690 BACKGROUND

• Jia L, Quan M, Fu Y, Zhao T, Li Y, Wei C, Tang Y, Qin Q, Wang F, Qiao Y, Shi S, Wang YJ, Du Y, Zhang J, Zhang J, Luo B, Qu Q, Zhou C, Gauthier S, Jia J; Group for the Project of Dementia Situation in China. Dementia in China: epidemiology, clinical management, and research advances. Lancet Neurol. 2020 Jan;19(1):81-92. doi: 10.1016/S1474-4422(19)30290-X. Epub 2019 Sep 4.

  PMID: 31494009 BACKGROUND

• Chatzi C, Zhang Y, Hendricks WD, Chen Y, Schnell E, Goodman RH, Westbrook GL. Exercise-induced enhancement of synaptic function triggered by the inverse BAR protein, Mtss1L. Elife. 2019 Jun 24;8:e45920. doi: 10.7554/eLife.45920.

  PMID: 31232686 BACKGROUND

• Lopez-Ortiz S, Valenzuela PL, Seisdedos MM, Morales JS, Vega T, Castillo-Garcia A, Nistico R, Mercuri NB, Lista S, Lucia A, Santos-Lozano A. Exercise interventions in Alzheimer's disease: A systematic review and meta-analysis of randomized controlled trials. Ageing Res Rev. 2021 Dec;72:101479. doi: 10.1016/j.arr.2021.101479. Epub 2021 Sep 30.

  PMID: 34601135 BACKGROUND

• He Z, Gao Y, Alhadeff AL, Castorena CM, Huang Y, Lieu L, Afrin S, Sun J, Betley JN, Guo H, Williams KW. Cellular and synaptic reorganization of arcuate NPY/AgRP and POMC neurons after exercise. Mol Metab. 2018 Dec;18:107-119. doi: 10.1016/j.molmet.2018.08.011. Epub 2018 Sep 12.

  PMID: 30292523 BACKGROUND

• Chapman SB, Aslan S, Spence JS, Hart JJ Jr, Bartz EK, Didehbani N, Keebler MW, Gardner CM, Strain JF, DeFina LF, Lu H. Neural mechanisms of brain plasticity with complex cognitive training in healthy seniors. Cereb Cortex. 2015 Feb;25(2):396-405. doi: 10.1093/cercor/bht234. Epub 2013 Aug 28.

  PMID: 23985135 BACKGROUND

• Hill NT, Mowszowski L, Naismith SL, Chadwick VL, Valenzuela M, Lampit A. Computerized Cognitive Training in Older Adults With Mild Cognitive Impairment or Dementia: A Systematic Review and Meta-Analysis. Am J Psychiatry. 2017 Apr 1;174(4):329-340. doi: 10.1176/appi.ajp.2016.16030360. Epub 2016 Nov 14.

  PMID: 27838936 BACKGROUND

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Officials

• Longfei Jia, MD,PhD

  Xuanwu Hospital, Beijing

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Longfei Jia, MD,PhD

CONTACT

+86 10 83199456; longfei@mail.ccmu.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 22, 2021
• First Posted: December 20, 2021
• Study Start: December 1, 2024
• Primary Completion (Estimated): December 1, 2034
• Study Completion (Estimated): December 1, 2034
• Last Updated: July 24, 2023

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)