Of 16 older adults recruited for this study, 8 were MCI (mean age: 79.5, 4 women, 7 caucasian) and 8 were cognitively normal (mean age 79.5, 3 women, all Caucasian). All participants were right handed, and all but two had more than 16 years of education. shows that MCI scored consistently worse than cognitively normal adults in each of the neuropsychological tests used to complete diagnosis of cognitive status. All patients were classified as multiple cognitive domain MCI by one of us (OL). All patients had 1 abnormal test result in at least two cognitive (not memory) domains. Six out of 8 patients also had abnormal results in at least 1 test of the memory domain.
Behavioral Response to the POP Task
Recording of behavioral responses was not completed for 2 individuals, and this precluded analysis of their reaction time or accuracy. However, for these two individuals the order of trial types, i.e., which trials were high- versus low-load, was available and allowed for functional MRI analysis.
In both groups, reaction times increased and accuracy rates decreased going from low-load to high-load conditions (). When going from low-to high-load condition, reaction time significantly increased in MCI (from 797.4 to 938.4 msec, z = −2.4, p = .01) and in cognitively normal subjects (from 697.4 to 817.2 msec, z= −2.02, p = .04) Small but consistent decrease in average accuracy rates was observed in MCI (98.6 to 95.8%, z = −.7, p = .4) and in cognitively normal subjects (97.8 to 92.1%, z = −2.1, p = .03) in response to task-load. Differences between groups were not significant for reaction times (low load: z = −.73, p = .5; high load: z = −.9, p = .4) nor for accuracy rates (low load: z = −.7, p = .5; high load: z = −1.1, p = .3).
Figure 2 Group Reaction time (RT) and Accuracy Rate (AR) during POP task in Cognitively Normal (CN) and MCI older adults (n = 8 and n = 6, respectively). Green and red indicate low load and high load condition, respectively. Boxplots indicate interquartile range (more ...)
Patterns of Brain Activation
Activation in MCI and cognitively normal subjects was measured in PPC, dlPFC and ACC (). Brain activation in response to high loads of the task substantially differed in MCI vs. Normal subjects in PPC and dlPFC (interaction of cognitive status by load: PPC: p = .001, dlPFC: p = .002), but not in ACC (interaction of cognitive status by load: p = .72). In MCI adults, PPC activation was significantly greater in high vs. low load (right: t7 = 3.5, p = .01; t7 = 2.7, left: .03), while in cognitively normal adults PPC-related activation did not substantially change with task- load (; right: t7 = 1.96, p = .09; t7 = 1.35, left: .22). In contrast, cognitively normal subjects responded to high load conditions by increasing dlPFC-related activation (; right hemisphere: t7 = 5.5, p = .0009; left hemisphere: t7 = 2.7, p = .03), while MCI did not (right: t7 = 1.8, p = .12, left: t7 = 1.24, p = .24). MCI showed significantly more activation compared to cognitively normal subjects both in PPC (low-load: t16 = 2.4, p = .03 and t16 = 2.2, p = .05 for right and left hemisphere; high-load: t16 = 3.1, p = .007 and t16 = 2.2, p = .04, for right and left hemisphere) and dlPFC (low-load condition: t16 = 3.7, p = .002 and t16 = 3.6, .004 for right and left hemisphere; high load condition: t16 = 2.1, p = .049 and t16 = 1.9, .08 for right and left hemisphere). Similar results were observed bilaterally for BA45, while activation was small or not significant in Brodmann area 9. In MCI adults, load related change in PPC activation was associated with worse performance on Amnart test (r = −.85, p = .007), and worse performance on Rey delayed recalled test (r = −.785, p = .02), word generation categories (r = −.8, p = .02) and Stroop color word test (r = .83, p = .01). Associations were not significant for cognitively normal subjects. In stepwise linear regression models, cognitive status alone explained 40% of the variance of PPC activation (right BA7). Cognitive status remained a significant and independent predictor of PPC activation after adjusting for Amnart score and education (t = 2.7, p = .02). Amnart score or education did not substantially change regression coefficients for cognitive status and dlPFC cortex. A modest load effect was observed in ACC () for cognitively normal subjects (p = .03), but not for MCI (p = .12). We did not detect a significant cognitive status effect (p = .8) nor a cognitive status by load interaction effect (p = .72) in this region.
Figure 3 Regions of Interest [upper row: (A– B)] included Brodmann area 7 (BA7), Brodmann area 46 (BA46) and Anterior Cingulate Cortex (ACC) as defined from our previous study (Carter et al 2000). Time Series activation (C– E) are illustrated for (more ...)
Association Between Brain Activation and Performance
Among older individuals with MCI, those with greater relative increase in PPC-derived signal (high- minus low-load related activation) also had smaller load-related changes in accuracy rates (partial correlation coefficients after adjustment for reaction time [p value]: r = −.85 [p = .07]) and greater relative increase in reaction time (partial correlation coefficients after adjustment for accuracy rates: r = .97, p = .01, ). In cognitively normal subjects, load-related change in PPC activation was associated with load-related change in reaction time (partial correlation coefficients after adjustment for accuracy rates [p value]: r = .76, p = .02, ) but not with accuracy rates (partial correlation coefficients after adjustment for reaction time [p value]: r = .09, [p = .4]), Greater load-related changes in dlPFC-derived signal was associated with smaller changes in reaction time () although associations were not statistically significant for MCI or for cognitively normal subjects (partial correlation coefficients = −.7 [p = .1] and −.5 [p = .2] after adjusting for accuracy rates). Associations between load-related change in dlPFC and accuracy rates were also not significant (MCI: r = .6, p = .2; cognitively normal subjects: r = .3 [p = .3]). Associations between relative increase in ACC activation and percent increase in reaction time or accuracy rates were not significant (partial correlation coefficient [p value]: r = .48 [p = .3], and r = −.6 [p = .8]).
Figure 4 Scatterplots of the association between increase in reaction time [RT] (high load – low load/low load) and increase in average fMRI signal change (high-load –low load) in PPC (right BA7) and dlPFC (right BA46). Gray triangles refer to (more ...)