Abstract
The current study investigates effects of normal aging, subjective/mild cognitive impairment (SCI/MCI) and apolipoprotein E gene (APOE) on different aspects of cognitive control. Cognitive control tasks were believed to be sensitive to distinguish normal aging vs. prodromal Alzheimer's disease (AD) processes. 679 healthy participants aged 18-79 (M = 48.2, SD = 18, Male/Female = 462/217), and 66 patients with diagnosis SCI/MCI aged 46-77 (M = 60.7, SD = 6.8, Male/Female = 34/32) were recruited, screened for exclusion criteria, tested on psychometric tests (Stroop, Matrix Reasoning, Digit Symbol, Letter-Number Span, TMT A, TMT B) and three different neuropsychological experiments (1: covert visuospatial orienting task, 2: context processing/updating task, 3: visuospatial working memory). Based on previous findings, non-additive effects of MCI+APOE ԑ4 were expected only on measures that activate the attentional reorienting system, i.e. cost of invalid cues in experiment 1, and BX-trials in experiment 2. Separate ANOVAs in the analysis were conducted with Group (Young Control (YC) aged 18-45, Old Control (OC) aged 46-79, MCI, aged 46-77), and APOE (+ԑ4, ÷ԑ4) as between-subject factors, and different within-subject factors for all three experiments based on cognitive theory. Effects of normal age (OC ÷ YC) were contrasted to effects of MCI (MCI ÷ OC), and different patterns of results were revealed on different tests. On all psychometric tests a decline of normal aging was found, and MCI exacerbated the decline in an additive way, with no APOE involvements. On visuospatial working memory, a similar pattern was found, that is: MCI added to the decline of normal age, with no modulations of APOE. However, on predicted component measures in experiment 1 & 2, MCI patients showed a performances pattern that seemed to be different (non-additive) from normal age effects. These effects were modulated by APOE in the MCI group only, indicating that APOEԑ4 played a specific role in pathological aging effects on these measures believed to activate the attentional reorienting system. The attentional reorienting system is activated by unexpected but behaviorally relevant targets, and modulated by both ventral and dorsal frontoparietal networks in the brain (Corbetta, Patel, & Shulman, 2008). It was discussed whether measures of the attentional reorienting system may be interpreted as a cognitive endophenotype, being an intermediate step in the APOE-AD link.