Combined Aerobic Exercise and Cognitive Training in Seniors With Genetic Susceptibility for Alzheimer's Disease

Official title

Combined Aerobic Exercise and Cognitive Training for Alzheimer's Disease Prevention in Seniors With Genetic Susceptibility Estimated by Polygenic Risk Models: Cognition and Neural Plasticity Effects

Overview

The study aims to investigate the effect of a long-term combined aerobic exercise and cognitive training program on cognitive function, daily function, psychosocial status, and neural plasticity in seniors with genetic susceptibility for Alzheimer's Disease.

Detailed description

Alzheimer's disease (AD) is the most common type of dementia and the leading cause of disability in people older than 65 years worldwide. However, there is no effective disease-modifying therapy currently. Therefore, improvement of cognitive function in people at risk and, potentially, prevention of cognitive decline has been gaining attraction.

Our previous research reported a model of a combination single nucleotide polymorphism (SNP) (rs3777215, rs234434, rs71352238, and rs4420638) can predict AD onset with high performance, which is useful to identify people at risk for AD and thus allows for timely treatment and prevention.

Both aerobic exercise and cognitive training have been demonstrated beneficial effects on cognition in subjects with AD and healthy populations. Moreover, the synergistic effects of the combination have been proven recently. However, the effect of combined aerobic exercise and cognitive training on seniors with genetic susceptibility for AD remains to be elucidated. Herein, this study aims to

1. assess the effects of long-term combined aerobic exercise and cognitive training on cognitive function, daily function, psychosocial status, and neural plasticity in seniors with single nucleotide polymorphism of rs3777215, rs234434, rs71352238, and rs4420638. 2. confirm the predictive value of the SNP model for AD in a longitudinal setting.

Interventions

• 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.

Primary outcome measures

• 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]
• 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]
• 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]
• Change in cognitive function over time as assessed by Verbal Fluency Test [Time frame: 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]
• 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]
• 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]
• 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]
• 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]
• The area under curve of the SNP model (rs3777215, rs234434, rs71352238 and rs4420638) for the accurate diagnosis of AD [Time frame: up to 7 years]

Secondary outcome measures (5)

• Change in whole brain volume as accessed by brain MRI [Time frame: baseline time, year 1, year 3, year 5, year 7]
• Change in daily function over time as assessed by Activities of daily living (ADL) [Time frame: baseline time, year 1, year 3, year 5, year 7]
• Change in anxiety over time as assessed by Hamilton Anxiety Rating Scale (HAMA) [Time frame: baseline time, year 1, year 3, year 5, year 7]
• Change in depression over time as assessed by Hamilton Depression Scale (HAMD) [Time frame: baseline time, year 1, year 3, year 5, year 7]
• Change in neuropsychiatric symptoms over time as assessed by Neuropsychiatric Inventory Questionnaire (NPI-Q) [Time frame: baseline time, year 1, year 3, year 5, year 7]

Eligibility criteria

Inclusion criteria

• Mandarin-speaking subjects.
• Not clinically demented.
• Meeting the cutoff values of MMSE and CDR.
• With positive variation of rs3777215, rs234434, rs71352238, and rs4420638.

Exclusion criteria

• Had major neurologic diagnosis (e.g., 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 disorder that can affect the ability to perform the proposed intervention tasks.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Prevention

Study locations

China · 1 center

• Xuanwu Hospital — Beijing

Publications

• Jia L, Li F, Wei C, Zhu M, Qu Q, Qin W, Tang Y, Shen L, Wang Y, Shen L, Li H, Peng D, Tan L, Luo B, Guo Q, Tang M, Du Y, Zhang J, Zhang J, Lyu J, Li Y, Zhou A, Wang F, Chu C, Song H, Wu L, Zuo X, Han Y, Liang J, Wang Q, Jin H, Wang W, Lu Y, Li F, Zhou Y, Zhang W, Liao Z, Qiu Q, Li Y, Kong C, Li Y, Jiao H, Lu J, Jia J. Prediction of Alzheimer's disease using multi-variants from a Chinese genome-wid PMID 33188687
• 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
• 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
• 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
• Ben Ayed I, Castor-Guyonvarch N, Amimour S, Naija S, Aouichaoui C, Ben Omor S, Tabka Z, El Massioui F. Acute Exercise and Cognitive Function in Alzheimer's Disease. J Alzheimers Dis. 2021;82(2):749-760. doi: 10.3233/JAD-201317. PMID 34092631

Identifiers

NCT: NCT05163067 · ICND20210820

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗