Lifelong cognitive reserve mitigates the genetic risk of APOE and TOMM40 variants for dementia in Chinese older adults: a cohort study
Xiaoyan Liang, Yuanjing Li, Rui Liu, Yifei Ren, Wenxin Fa, Min Zhu, Keke Liu, Cuicui Liu, Nan Wang, Na Tian, Yongxiang Wang, Lin Cong, Tingting Hou, Yifeng Du, Chengxuan Qiu- Psychiatry and Mental health
- Cellular and Molecular Neuroscience
- Geriatrics and Gerontology
- Neurology (clinical)
- Developmental Neuroscience
- Health Policy
- Epidemiology
Abstract
Background
Evidence has emerged that cognitive reserve (CR) could mitigate the genetic risk of APOE ε4 allele for dementia and Alzheimer’s disease (AD) in Caucasian and Black populations. Whether CR counteracts dementia risk attributable to TOMM40 variants is unknown. We examined whether lifelong CR might modify the risk of dementia and AD from APOE and TOMM40 variants among Chinese older adults.
Method
This population‐based cohort study included 2052 dementia‐free participants from the Shandong Yanggu Study of Aging and Dementia, who were free of dementia at baseline (2014‐2015) and underwent follow‐up examinations in March‐September 2018. APOE (rs429358 and rs7412) and TOMM40 (rs2075650) were defined using multiple polymerase chain reaction amplification. A lifelong composite CR score was generated from six lifespan intellectual factors and then dichotomized into high and low levels according to the median CR score. Dementia and AD were clinically diagnosed following the international criteria. Data were analyzed using Cox proportional‐hazards models. The interaction between CR and APOE or TOMM40 variants was assessed on multiplicative and additive scales.
Result
During an average of 3.72 years (range, 2.98‐4.46) of follow‐up, dementia was diagnosed in 94 persons, including 70 with AD. Overall, carrying APOE e4 allele (vs. non‐carriers) was associated with multivariable‐adjusted hazard ratio of 1.50 (95%CI: 0.91‐2.50) for dementia and 1.71 (0.97‐3.01) for AD; the corresponding figures were 1.76 (1.09‐2.85) and 1.81 (1.04‐3.15) for carrying TOMM40 G allele (vs. AA), and 0.47 (0.27‐0.80) and 0.52 (0.27‐0.996) for high CR, respectively. There was a significant additive interaction of APOE or TOMM40 variants with CR on risks of dementia and AD. Compared to low CR, having high lifelong CR was associated with a lower risk of developing dementia and AD in APOE e4 carriers, with multivariable‐adjusted hazard ratios being 0.17 (95%CI: 0.04‐0.73) and 0.13 (0.02‐1.02); the corresponding figures were 0.23 (0.07‐0.81) and 0.13 (0.02‐1.02) in TOMM40 G carriers, and 0.22(0.06‐0.74) and 0.12(0.02‐0.91) in APOE‐e4 or TOMM40 G carriers, respectively.
Conclusion
Carrying TOMM40 G or APOE e4 allele is associated with increased risks of dementia and AD in Chinese older adults, and the genetic risk could be counteracted by high lifelong CR capacity.