La implantación de la PRL en los respectivos Ejércitos de Tierra

The neurological underpinnings of executive dysfunction in MCI and AD remain unclear. However, the lack of clear frontal lobe atrophy in the early stages of the disease suggests that these deficits may arise from a disruption of neural networks supporting executive functioning. Recent structural neuroimaging studies that have explored the relationship between

neuropathology and cognition in AD and MCI have typically found that executive functioning is associated with broad measures of neuropathology, such as whole-brain atrophy, ventricular enlargement, and cortical thickness in multiple brain regions (Braskie & Thompson, 2013; Chang et al., 2010; Vasconcelos et al., 2014) as well as changes in white matter (T.-F. Chen et al., 2009; Maillard et al., 2012; Marra, Ferraccioli, Vita, Quaranta, & Gainotti, 2011; Reijmer et al., 2013). In a study that examined the relationship between Stroop performance and amyloid plaques and neurofibrillary tangles at autopsy, there was a relationship between the interference

score on the Stroop and neurofibrillary tangles in the hippocampus and superior temporal cortex (Bondi et al., 2002). No association was found with tangles in the inferior parietal cortex or midfrontal cortex or with amyloid plaques in any of the four regions examined.

Functional neuroimaging studies in MCI and AD have produced variable results. For example, reduced activation has been reported in frontal and parietal regions in MCI patients during a visuospatial working memory task (Alichniewicz, Brunner, Klünemann, & Greenlee, 2012), whereas increased frontal and parietal activation has been reported during the Stroop task (C. Li, Zheng, Wang, Gui, & Li, 2009). There is some evidence that compensatory increases in activation may occur in the early stages of MCI, but that during the later stages, compensatory increases are no longer present and decreases in activation may begin to appear. Clément et al. (2013) examined fMRI activation during the performance of manipulation and divided attention tasks in early- and late-stage MCI patients and found increased activation in early-stage MCI patients in mainly prefrontal regions during the manipulation task and in a fronto-striatal network during the divided attention task. This increased frontal activation was associated with better performance on executive tasks; however, MCI patients did exhibit a deficit on task performance in comparison to controls. In contrast, late-stage MCI patients exhibited hypoactivation of prefrontal and occipito-temporal areas during the performance of the manipulation task and there were no differences in activation between late-stage MCI patients and controls on the divided attention task. In addition, there were no significant correlations between cognitive performance and activation in the late-stage MCI group. Thus, compensatory increases in activation may be present in the earliest stages of the illness, with a breakdown of these processes occurring as the disease progresses.

In AD patients, decreased frontal activation in conjunction with increased parietal activation has been observed during the performance of the N-back task of working memory (Lim et al., 2008) and decreased prefrontal activation has been observed during the Stroop task (C. Li et al., 2009). Furthermore, both MCI patients and AD patients show decreased

deactivation of the default mode network during the performance of the N-back task, with deactivations in MCI patients being intermediate between controls and AD patients for anterior frontal regions and similar to AD patients in the precuneus (Rombouts et al., 2005).

Collette et al. (1999) examined the relationship between executive dysfunction and cerebral metabolism at rest in AD. They found a positive correlation between a factor

representing inhibitory control and metabolism in the middle and superior frontal gyrus. In contrast, a factor representing working memory was associated with metabolism in the posterior cingulate, middle temporal region, and parietal areas. In a recent study, a composite executive functioning score was associated with hypometabolism in parietal and temporal regions, but not frontal regions in both MCI and AD patients (Habeck et al., 2012). However, frontal metabolism in addition to parietal and temporal metabolism has been associated with performance on other executive tasks, such as the clock drawing task (Shon et al., 2013), the Stroop task (Yun et al., 2011), dual task performance (Laine et al., 2009), and measures of abstract reasoning, fluency, and planning (Woo et al., 2010). Thus, both frontal and non-frontal (particularly in temporo- parietal) regions appear to be involved in executive functioning in MCI and AD. However, frontal dysfunction does not appear to be necessary to produce executive dysfunction in these groups. This was demonstrated by Collette et al. (Collette, Van der Linden, Delrue, & Salmon, 2002), who examined two groups of AD patients: those with hypometabolism restricted to parietal and temporal regions and those with both frontal and posterior hypometabolism. They examined their performance on a variety of executive tasks including tasks of inhibitory control, verbal fluency, and selective attention, and they found that AD patients in both groups performed worse than controls on all of the executive tasks, whether frontal hypometabolism was present or not. Once again, this is evidence supporting the hypothesis that executive dysfunction in AD may be a consequence of disconnection between anterior and posterior regions.

The relationship between brain functioning and cognitive functioning may continue to change as the disease progresses. Bracco et al. (2007) examined the metabolic correlates of executive functioning in mild and very mild AD and found that executive measures were

associated with prefrontal metabolism in very mild AD patients, whereas parietal, temporal, and occipital areas were more strongly associated with executive measures in the mild AD patients. Thus, the relationship between cognition and brain functioning in MCI and AD is complex and depends on a variety of factors. For example, the stage of the illness may play an important role, with potentially significant differences in the association between brain and cognitive function even within diagnostic groups. Furthermore, individual differences in neurocognitive reserve and successful or unsuccessful neural compensation mechanisms may also play an important role. However, overall, the present state of the literature points to the importance of neural networks connected with the frontal lobes in supporting executive functioning and that disruption of these

networks is related to executive dysfunction in MCI and AD. The disconnection hypothesis can be more directly tested using EEG coherence, which is particularly useful for exploring network functioning, given the high temporal resolution of the EEG signal.