Maximal brain size remains an important predictor of cognition in old age, independent of current brain pathology

Abstract

There is growing interest in the influence of early-life development on clinical manifestations of late-life diseases. Latent variable modeling was used to investigate how maximal brain volume (measured by intracranial volume [ICV]) and current brain volumes uniquely contribute to domain-specific cognitive performance in a group of 401 cognitively and ethnically diverse older adults. Individual effects of volumetric magnetic resonance imaging (MRI) measures including ICV were examined as predictors of episodic memory, semantic memory, spatial ability, and executive function. Total brain matter volume related to all cognitive domains; hippocampal volume was associated primarily with episodic memory; white matter hyperintensity volume was related to executive function and episodic memory. Maximal brain size as measured by ICV was related to semantic memory, executive function, and spatial ability independent of current brain volumes (ps < 0.01). Relationships between magnetic resonance imaging (MRI) variables and cognition did not differ substantially across groups defined by ethnicity, gender, and with minor exceptions, clinical diagnosis. Results suggest maximal brain development and measures of brain injury/atrophy jointly contribute to cognitive function in older people.

Figure 1. Analytic model

Rectangles refer to observed variables and ovals represent latent variables; observed variables are labeled with capital letters, latent variables with lower case. Latent variables models can be conceptualized as multiple, simultaneously estimated linear regressions; each path depicted by a line corresponds to a regression of the variable at the (arrow) end of the line on the variable at the (non-arrow) beginning of the line. Lines correspond to freely estimated model parameters and the values for fixed model parameters are presented.