Episodic memory and executive functions in cognitively healthy individuals display distinct neuroanatomical correlates which are differentially modulated by aging

Abstract

The neuroanatomical bases of episodic memory (EM) and executive functions (EFs) have been widely addressed in patients with brain damage and in individuals with neurologic disorders. These studies reported that larger brain structures support better outcomes in both cognitive domains, thereby supporting the “bigger is better” account. However, relatively few studies have explored the cerebral morphological properties underlying EM and EFs in cognitively healthy individuals and current findings indicate no unitary theoretical explanation for the structure–function relationship. Moreover, existing studies have typically restricted the analyses to a priori defined regions of interest. Here we conducted unbiased voxel‐wise analysis of the associations between regional gray as well as white matter volumes (GMv; WMv) and performance in both cognitive domains in a sample of 463 cognitively intact individuals. We found that efficiency in EM was predicted by lower GMv in brain areas belonging to the default‐mode network (DMN). By contrast, EFs performance was predicted by larger GMv in a distributed set of regions, which overlapped with the executive control network (ECN). Volume of white matter bundles supporting both cross‐cortical and interhemispheric connections was positively related to processing speed. Furthermore, aging modulated the relationship between regional volumes and cognitive performance in several areas including the hippocampus and frontal cortex. Our data extend the critical role of the DMN and ECN by showing that variability in their morphological properties, and not only their activation patterns, affects EM and EFs, respectively. Moreover, our finding that aging reverts these associations supports previously advanced theories of cognitive neurodevelopment.

Tau Protein is Associated with Longitudinal Memory Decline in Cognitively Healthy Subjects with Normal Alzheimer’s Disease Cerebrospinal Fluid Biomarker Levels

“…In normal aging, the posterior cerebellar lobes show accelerated volume reduction with respect to other structures [62], and this reduction may be more relevant to cognitive performance than typically shown by studies of diseased patients with cortical lesions. In line with our results, other recent studies including similarly aged and cognitively healthy cohorts [63][64][65] show involvement of the cerebellum in memory and executive function tests. Taken together, our findings showed structural correlates of cognitive performance in a well-characterized sample of subjects with normal cognition and normal AD CSF biomarker levels, providing evidence on the most vulnerable brain systems related to learning and memory in aging.…”

White matter hyperintensities mediate gray matter volume and processing speed relationship in cognitively unimpaired participants

“…Concerning EM, even though we found significant relationship between GMv and WMH in regions involved in this cognitive domain, such as hippocampus, we did not find a significant mediation effect. This result is in line with previous work (Cacciaglia, Molinuevo, Sánchez‐Benavides, et al, ) suggesting that this area shows a relatively low involvement in MBT performance.…”

“…However, to the best of our knowledge, no previous research has looked at for the joint impact of both WMH and GMv on cognition using voxel‐wise approach (Rizvi et al, ; Wen et al, ). Regarding path c , we had previously established in this cohort that EM and EF rely on nonoverlapping cerebral structural networks (Cacciaglia, Molinuevo, Sánchez‐Benavides, et al, ).…”

“…An additional factor that could explain such a discrepancy might be the test that we used to measure EM (MBT), whose characteristics may differ from those of the other memory tests used in similar reports. We previously showed that, in cognitively unimpaired middle‐aged participants, better EM performance was significantly associated with lower GMv in several brain regions modulated by aging (Cacciaglia, Molinuevo, Sánchez‐Benavides, et al, ). This result is consistent with earlier research in which WMH are mainly related to frontal‐type dysfunction including impairments in attention, and processing speed (Desmond, ; Kloppenborg et al, ).…”

“…Cross‐sectional studies have also revealed a regional relationship between GMv and cognition in cognitively unimpaired individuals (Duarte et al, ; Tuladhar et al, ). In this context, the brain structural networks supporting EM and EF appeared to be spatially segregated and did not show overlap cerebral networks (Cacciaglia, Molinuevo, Sánchez‐Benavides, et al, ). As efforts to reduce the global burden of dementia progressively shift toward prevention, a better understanding of the mechanisms linking WMH with neurodegeneration is of utmost importance (Prins & Scheltens, ; Winblad et al, ).…”