Clinical trial NCT05163067: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Alzheimer Disease
Keywords: Alzheimer's disease
cognitive training
prevention
aerobic exercise
genetic susceptibility
neural plasticity
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, 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.

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.

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 California Verbal Learning Test (CVLT)
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: The area under curve of the SNP model (rs3777215, rs234434, rs71352238 and rs4420638) for the accurate diagnosis of AD
timeFrame: up to 7 years
Secondary outcomes:
measure: Change in whole brain volume as accessed by brain MRI
timeFrame: baseline time, year 1, year 3, year 5, year 7
measure: Change in daily function over time as assessed by Activities of daily living (ADL)
timeFrame: baseline time, year 1, year 3, year 5, year 7
measure: Change in anxiety over time as assessed by Hamilton Anxiety Rating Scale (HAMA)
timeFrame: baseline time, year 1, year 3, year 5, year 7
measure: Change in depression over time as assessed by Hamilton Depression Scale (HAMD)
timeFrame: baseline time, year 1, year 3, year 5, year 7
measure: Change in neuropsychiatric symptoms over time as assessed by Neuropsychiatric Inventory Questionnaire (NPI-Q)
timeFrame: baseline time, year 1, year 3, year 5, year 7
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, 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-wide association study. Brain. 2021 Apr 12;144(3):924-937. doi: 10.1093/brain/awaa364.
citation: 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.
citation: 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.
citation: 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.
citation: 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.