Neuroanatomical substrates of age-related cognitive decline

Abstract

There are many reports of relations between age and cognitive variables and of relations between age and variables representing different aspects of brain structure and a few reports of relations between brain structure variables and cognitive variables. These findings have sometimes led to inferences that the age-related brain changes cause the age-related cognitive changes. Although this conclusion may well be true, it is widely recognized that simple correlations are not sufficient to warrant causal conclusions, and other types of correlational information, such as mediation and correlations between longitudinal brain changes and longitudinal cognitive changes, also have limitations with respect to causal inferences. These issues are discussed, and the existing results on relations of regional volume, white matter hyperintensities, and diffusion tensor imaging measures of white matter integrity to age and to measures of cognitive functioning are reviewed. It is concluded that at the current time the evidence that these aspects of brain structure are neuroanatomical substrates of age-related cognitive decline is weak. The final section contains several suggestions concerning measurement and methodology that may lead to stronger conclusions in the future.

Figure 1

Means (and standard errors) in different cognitive variables (top panel), and standard deviations corresponding to the means (bottom panel) as a function of age in cross-sectional comparisons in two projects. The panels on the left portray data from projects by Salthouse (2010a, 2010b, 2010c), and those on the right portray data from Ronnlund et al. (2005, 2006).

Figure 2

Means (and standard errors) of longitudinal changes in different cognitive variables (top panel), and standard deviations corresponding to the means (bottom panel) as a function of age in two projects. The panels on the left portray data from projects by Salthouse (2010a, 2010b, 2010c), and those on the right portray data from Ronnlund et al. (2005, 2006).

Figure 3

Schematic illustration of correlations among age, brain, and cognitive variables (top), and four models of the relations among the variables which could produce the correlations.

Figure 4

Schematic illustration of three models of the relations among the A, B, and C variables, and the relation (dotted line) hypothesized to be small or non-existent according to the model.

Figure 5

Illustration of univariate (top panel) and multivariate (bottom panel) analyses of the relations among A, B, and C variables. Note that in the bottom panel both specific (dotted lines) and general (involving the circled B and C variables) relations are examined.