Genetic complexity of episodic memory: A twin approach to studies of aging.

Abstract

Episodic memory change is a central issue in cognitive aging, and understanding that process will require elucidation of its genetic underpinnings. A key limiting factor in genetically informed research on memory has been lack of attention to genetic and phenotypic complexity, as if “memory is memory” and all well-validated assessments are essentially equivalent. Here we applied multivariate twin models to data from late-middle-aged participants in the Vietnam Era Twin Study of Aging to examine the genetic architecture of 6 measures from 3 standard neuropsychological tests: the California Verbal Learning Test-2, and Wechsler Memory Scale-III Logical Memory (LM) and Visual Reproductions (VR). An advantage of the twin method is that it can estimate the extent to which latent genetic influences are shared or independent across different measures before knowing which specific genes are involved. The best-fitting model was a higher order common pathways model with a heritable higher order general episodic memory factor and three test-specific subfactors. More importantly, substantial genetic variance was accounted for by genetic influences that were specific to the latent LM and VR subfactors (28% and 30%, respectively) and independent of the general factor. Such unique genetic influences could partially account for replication failures. Moreover, if different genes influence different memory phenotypes, they could well have different age-related trajectories. This approach represents an important step toward providing critical information for all types of genetically informative studies of aging and memory.

Immediate verbal recall and familial dementia risk: population-based study of over 4000 twins

“…This is in line with an earlier study reporting a heritability of 0.36 for word list learning measure including multiple trials (CVLT) 20. However, the first trial of the 16-item word list (CVLT) has been reported to show zero heritability indicating that a single-trial administration of a word list may not be reliable enough to show consistent heritability 21. In our study, the 10-item word list was presented only once but still showed substantial heritability.…”

Genetic and environmental architecture of changes in episodic memory from middle to late middle age.

“…To address the issue of confounding of genetic influences on episodic memory by genetic influences on GCA, we adjusted all memory measures for GCA prior to the twin analyses (Kremen et al, 2014). The adjusted (residual) scores were then used in the twin analyses.…”

“…The second model, the Longitudinal Factor Model , extends our previously described higher-order common pathways model of episodic memory to two measurement timepoints (Kremen et al, 2014), and provides the opportunity to test the invariance of the factor structure across time as well as the stability of the latent phenotypes. As depicted in Figure 1, the identical factor structure is specified to the data from VETSA1 and VETSA2, and the genetic and environmental determinants of all latent factors, and the observed variables are allowed to correlate across time.…”

“…Because factor structures are not necessarily the same at the phenotypic and genetic levels, our approach was to directly determine the best-fitting genetic model (Kremen et al, 2014; Panizzon et al, 2014). Memory measures were adjusted for general cognitive ability (GCA) in order to determine variance associated specifically with episodic memory.…”

Genetics and neuropsychology: A merger whose time has come.

“…Both represent complex, multidimensional and multi-determined phenotypes with their own complex genetic architectures (Flint & Munafò, 2007; W.S. Kremen et al, 2007; W. S. Kremen et al, 2014; Papassotiropoulos & de Quervain, 2011).…”