Clues To The Genetics of Memory Function in Elderly Revealed in New Study

A large study entitled “Genome-wide studies of verbal declarative memory in non-demented older people: the CHARGE consortium” was recently published in the journal Biological Psychiatry and sought to identify the genetics of memory function in older individuals.

One of the most essential aspects of human cognition is the ability to form and retrieve memories. In late life, severe cognitive decline in memory is one of the early signs of dementia. The conscious recall of information and its verbalization is called verbal declarative memory, and delay in this task has been found in studies to be a strong predictor of Alzheimer disease. Additionally, evidence shows that there is a genetic component in verbal memory performance, however, there is a lack of studies showing consistent results in which genetics are effectively associated. Three genome-wide association studies (GWAS) with young people found associations of genetic variants in the KIBRA and CTNNBL1 genes with verbal declarative memory delayed recall.  However, there is a lack of GWAS studies involving verbal declarative memory-delayed recall performance in older individuals.

To address this lack of evidence, the team of researchers led by Thomas Mosley, Ph.D., director of the MIND Center at UMMC, conducted a meta-analysis of GWAS for verbal declarative memory-delayed recall performance in a sample of 29,076 older individuals, and compared the findings in 13,998 independent older participants (10,617 of European descent and 3,381 African-Americans) and 1,561 young adults.

Results revealed an association of genetic variants near the Apolipoprotein E gene, with poor memory performance in the group above 65 years old.

Moreover, the team of researchers found two additional genome-wide associations in a sub-study using post-mortem brain samples. HS3ST4 and SPOCK3 were identified, and other putative modulators of memory performance were revealed by a pathway approach and hippocampal gene expression analyses, although this study approach still needs replication.

To date, this was the largest study (approximately 40,000 individuals) exploring the genetics foundations of memory function with results revealing that are genome-wide associations and an involvement of immune and ubiquitin pathways.

In a recent press release, the lead author Stéphanie Debette, M.D., Ph.D., an adjunct associate professor at Boston University School of Medicine, stated “Interestingly genetic variants associated with memory performance also predicted altered levels of expression of certain genes in the hippocampus, a key region of the brain for the consolidation of information,” “These were mainly genes involved in the metabolism of ubiquitin that plays a pivotal role in protein degradation,” she added.

Additionally, Dr. Mosley said “The findings need to be carefully replicated and we need a much better understanding of the function of these genetic sites. Identifying susceptibility regions is only a first step, but an important one, because understanding the mechanisms underlying susceptibility regions may ultimately lead to the development of new treatments for memory loss.”