Clinical trial NCT05163626: Combined Aerobic Exercise and Cognitive Training in Seniors at Increased Risk for Alzheimer's Disease
Official title: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Alzheimer Disease
Keywords: Alzheimer's disease
aerobic exercise
exosome
synaptic protein
biomarker
prevention
cognitive training
Lead sponsor: Xuanwu Hospital, Beijing
Sponsor class: OTHER
First posted: 2021-12-20
Enrollment: 200
Sex: ALL
Minimum age (years): 50
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in cognitive function over time as assessed by the Montreal Cognitive Assessment (MoCA)
timeFrame: baseline time, year 1, year 3, year 5, year 7
measure: Change in cognitive function over time as assessed by Mini Mental State Examination (MMSE)
timeFrame: baseline time, year 1, year 3, year 5, year 7
measure: Change in cognitive function over time as assessed by Clinical Dementia Rating (CDR)
timeFrame: baseline time, year 1, year 3, year 5, year 7
measure: Change in cognitive function over time as assessed by Verbal Fluency Test
timeFrame: baseline time, year 1, year 3, year 5, year 7
measure: Change in cognitive function over time as assessed by Digit Span Test-Forward and Backward
timeFrame: baseline time, year 1, year 3, year 5, year 7
measure: Change in cognitive function over time as assessed by Trail-Making Test Parts A and B (TMT-A and TMT-B)
timeFrame: baseline time, year 1, year 3, year 5, year 7
measure: Change in cognitive function over time as assessed by Boston Naming Test (BNT)
timeFrame: baseline time, year 1, year 3, year 5, year 7
measure: Change in cognitive function over time as assessed by the Rey-Osterrieth Complex Figure Test (ROCF)
timeFrame: baseline time, year 1, year 3, year 5, year 7
measure: Change in cognitive function over time as assessed by California Verbal Learning Test (CVLT)
timeFrame: baseline time, year 1, year 3, year 5, year 7
Secondary outcomes:
measure: Changes in concentrations of blood neuro-exosomal GAP43 over time
timeFrame: baseline time, year 1, year 3, year 5, year 7
measure: Changes in concentrations of blood neuro-exosomal neurogranin over time
timeFrame: baseline time, year 1, year 3, year 5, year 7
measure: Changes in concentrations of blood neuro-exosomal SNAP25 over time
timeFrame: baseline time, year 1, year 3, year 5, year 7
measure: Changes in concentrations of blood neuro-exosomal synaptotagmin1 over time
timeFrame: baseline time, year 1, year 3, year 5, year 7
measure: The area under curve of the blood neuro-exosomal synaptic proteins (GAP43, neurogranin, SNAP25, and synaptotagmin1) for the accurate diagnosis of AD
timeFrame: up to 7 years
Other outcomes:
Locations:
city: Beijing
country: China
facility: Xuanwu Hospital
Study officials:
affiliation: Xuanwu Hospital, Beijing
name: Longfei Jia, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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