Genetic risk factors in cogntive decline

Evaluating the association of genetic risk factors with cognitive decline

Late-onset Alzheimer’s disease (LOAD) susceptibility genes are good candidates for association with cognitive decline, as the pathological features of LOAD progress to varying degrees in individuals without dementia or cognitive impairment. However, to date, studies investigating the role of AD risk loci in cognitive decline have been characterized by a lack of consensus. I investigated the role of known genetic variants associated with LOAD in cognitive function. This research improved upon previous studies by using a large well-characterized cohort with 12 years of follow-up, and with participants undergoing a comprehensive neuropsychological battery. It was observed that a subset of the AD risk loci were associated with cognitive function, however, the effect sizes were small, and when demographic and lifestyle factors are taken into account, neither individual SNPs nor a genetic risk score explained a meaningful proportion of the variance in cognitive decline in our sample. Additionally, in a systematic review of the literature (currently under review), we do not support a consistent association between individual non-APOE LOAD risk and cognitive performance or decline. However, evidence suggests that aggregate LOAD genetic risk exerts deleterious effects on decline in episodic memory and global cognition. This research indicates that individual AD-related genetic markers may have limited utility in identifying individuals at risk of cognitive decline. In contrast, genetic risk scores may offer more utility in predicting cognitive decline and impairment.

Selected Publications:

  1. Andrews SJ, Das D, Cherbuin N, Anstey KJ, Easteal S. (2016). Association of genetic risk factors with cognitive decline: The PATH through life project. Neurobiology of Aging. 41: 150-158. PubMed PMID: 27103528
  2. Andrews SJ, Das D, Anstey KJ, Easteal S. (2017). Association of AKAP6 and MIR2113 with cognitive performance in a population based sample of older adults. Genes, Brain and Behavior. 16(4): 472-478. PubMed PMID: 28067462
  3. Andrews SJ, Das D, Anstey KJ, Easteal S (2017). Late Onset Alzheimer’s disease risk variants in cognitive decline: The PATH Through Life Study. Journal of Alzheimer’s disease. 57:423-436. PubMed PMID: 28269768