Memory is Not Enough: The Neurobiological Substrates of Dynamic Cognitive Reserve

Abstract

Changes in the residual memory variance are considered as a dynamic aspect of cognitive reserve (d-CR). We aimed to investigate for the first time the neural substrate associated with changes in the residual memory variance overtime in patients with amnestic mild cognitive impairment (aMCI). Thirty-four aMCI patients followed-up for 36 months and 48 healthy elderly individuals (HE) were recruited. All participants underwent 3T MRI, collecting T1-weighted images for voxel-based morphometry (VBM). They underwent an extensive neuropsychological battery, including six episodic memory tests. In patients and controls, factor analyses were used on the episodic memory scores to obtain a composite memory score (C-MS). Partial Least Square analyses were used to decompose the variance of C-MS in latent variables (LT scores), accounting for demographic variables and for the general cognitive efficiency level; linear regressions were applied on LT scores, striping off any contribution of general cognitive abilities, to obtain the residual value of memory variance, considered as an index of d-CR. LT scores and d-CR were used in discriminant analysis, in patients only. Finally, LT scores and d-CR were used as variable of interest in VBM analysis. The d-CR score was not able to correctly classify patients. In both aMCI patients and HE, LT1st and d-CR scores showed correlations with grey matter volumes in common and in specific brain areas. Using CR measures limited to assess memory function is likely less sensitive to detect the cognitive decline and predict the evolution of Alzheimer's disease. In conclusion, d-CR needs a measure of general cognition to identify conversion to Alzheimer's disease efficiently.

Cognitive reserve: the evolution of the conceptual framework

“…Reed and co-workers [13] proposed the concept of dynamic CR, measured in terms of changes in memory functions. Zahodne and colleagues [14,15] and Serra and co-workers [16] extended the concept of dynamic CR. These studies quantified CR as residual variance of memory scores, after accounting for demographical and brain damage variables.…”

“…To conceptualize CR in terms of residual variance of memory functions made the CR's concept more flexible and adaptable to cognitive changes. However, Serra and co-workers [16] have recently shown that indices of dynamic CR that strip off any contribution of general cognitive abilities to retain exclusively memory processes are not able to identify the conversion to AD efficiently. The integrity of memory function is not sufficient to withstand neurodegeneration [16].…”

“…However, Serra and co-workers [16] have recently shown that indices of dynamic CR that strip off any contribution of general cognitive abilities to retain exclusively memory processes are not able to identify the conversion to AD efficiently. The integrity of memory function is not sufficient to withstand neurodegeneration [16]. By contrast, the ability to use synergistically the different cognitive functions is protective against the conversion to AD.…”

“…Also cognitive performances, such as the intelligence quotient (IQ) [12], memory performances, executive functioning, have been considered as proxy measures of CR [5]. More recently, reserve indexes have been categorised as static and dynamic proxy measure [13][14][15][16]. Years of formal education, occupational attainment, pre-morbid IQ and leisure activities pursued during childhood-adolescence and early adulthood life period, have been considered static measures, because they are not directly able to capture the individual cognitive changes.…”

“…Years of formal education, occupational attainment, pre-morbid IQ and leisure activities pursued during childhood-adolescence and early adulthood life period, have been considered static measures, because they are not directly able to capture the individual cognitive changes. Conversely, memory performances and executive functioning have been considered as dynamic measure because they reflect directly cognitive measure [13][14][15][16].…”