Exceptional Memory Performance in Elders Linked to Candidate Gene

Brandy R. Matthews, MD

Genetic analyses identify a region, 6q24, implicated in norepinephrine synthesis.

Genetic factors, such as APOE alleles, that place individuals at increased risk for Alzheimer disease and for poor episodic memory performance in the context of aging are well known. Less is known about genetic factors that may lead to excellent memory performance in elders. Familial aggregation of exceptional episodic memory (EEM) has been reported in the Long Life Family Study (LLFS). To explore this finding in more detail, researchers performed a genome-wide linkage in 18 EEM families from LLFS (467 individuals) and followed up with single-nucleotide polymorphism (SNP) analysis using episodic memory scores (mean of standardized Logical Memory IA and IIA) in four independent, well-characterized elderly cohorts without dementia (n=4006).

A region on chromosome 6q24 was linked to EEM via genome-wide linkage analysis. The replication-cohort analysis identified 26 episodic memory–associated SNPs within this region. Meta-analysis in the four independent replication cohorts identified two SNPs (rs9321334 and rs6902875) associated with episodic memory. When individuals with an APOE E4 allele were eliminated from the analysis, SNP rs6902875 became highly statistically significant. Several gene candidates in the region of this SNP are biologically plausible effectors of exceptional episodic memory, including MOXD1, a gene involved in the biosynthesis of norepinephrine.

Citation(s):

Barral S et al. Common genetic variants on 6q24 associated with exceptional episodic memory performance in the elderly. JAMA Neurol 2014 Oct 13; [e-pub ahead of print].