Brain oscillations in cognitive control: a cross-sectional study with a spatial Stroop task

An important aspect of cognitive control is the ability to overcome interference, by boosting the processing of task-relevant information while suppressing the irrelevant information. This ability is affected by the progressive cognitive decline observed in aging. The aims of this study were to shed light on the neural spectral dynamics involved in interference control and to investigate age-dependent differences in these dynamics. For these reasons two samples of participants of different ages (23 younger and 20 older adults, age range=[18 35] and [66 82], respectively) were recruited and administered a spatial Stroop task while recording electroencephalographic activity. Scalp- and source-based time-frequency analyses revealed a main role of theta and beta frequencies in interference control. Specifically, for the theta band, we found age-dependent differences both for early event-related spectral perturbation (ERSP) Stroop effects at the source level \u2013 which involved dorsomedial and dorsolateral prefrontal cortices \u2013 and for related brain-behaviour correlations. This ERSP Stroop effect in theta was greatly reduced in magnitude in the older group and, differently from what observed in younger participants, it was not correlated with behavioural performance. These results suggest an age-dependent impairment of the theta-related mechanism signalling the need of cognitive control, in line with existing findings. We also found age-related differences in ERSP and source spectral activity involving beta frequencies. Indeed, younger participants showed a specific ERSP Stroop effect in beta \u2013 with the main involvement of left prefrontal cortex \u2013 whereas the pattern of older participants was delayed in time and spread bilaterally over the scalp. This study shows clear age-related differences in the neural spectral correlates of cognitive control. These findings open new questions about the causal involvement of specific oscillations in different cognitive processes and may inspire future interventions against age-related cognitive decline

Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

Aims  The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results  Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion  After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p

Effect of alirocumab on mortality after acute coronary syndromes. An analysis of the ODYSSEY OUTCOMES randomized clinical trial

Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≥3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events (P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined wit h achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402

Normal aging effects in a priming-free Stroop test

The present study investigated age differences in selective attention and the modulatory effect that variables such as verbal and spatial intelligence have on its decline.We used a Stroop colour test with no feature repetitions between subsequent trials to avoid priming effects. Sixteen healthy older (65-79 years, 8 females, MMSE=28-30/30) and sixteen younger (18-34 years, 8 females) volunteers participated in the study. The two age-groups were matched for education years and for four WAIS-R subtests (Wechsler, 1981): Block Design, Arithmetic, Vocabulary and Similarities. Error percentage was similar in the two groups [<4%, F(1,30)=.04, p=.84]. A classical Stroop effect was instead present in both younger [t(15)=-5.34, p<.001] and older adults [t(15)=-12.45, p<.001]. Older adults were 250 ms slower than younger controls, even after the data were logarithmically transformed to partially correct for general slowing [F(1,30)=58.89, p<.001]. The older group suffered from the word-colour Stroop interference more than younger adults as shown by the interaction between age and congruency [F(1,30)=20.44, p<.01]. This finding confirms that older adults have difficulty in ignoring non-target features (colour word) with respect to a target feature (word colour). However, a negative correlation between Similarities test scores and Stroop effect in the older group (r= -.58, p<.05) was obtained, indicating that those older adults with higher verbal similarities scores are those who cope better with Stroop interference. This finding suggests that there is a specific type of cognitive reserve, probably related to verbal intelligence, which preserves selective attention in normal aging

Age-related conflict resolution deficit: compensatory roles of intelligence, cognitive reserve and education

The aim of this study was to investigate whether resolution of conflict in different domains is affected by normal aging and whether factors such as cognitive reserve, years of education and intelligence compensate for age-related deficits. Two experiments with partially overlapping samples, both including non-demented older adults (65-79 years old, N=23 and 17) and younger controls (18-34 years old, N=22 and 18), performed verbal and spatial Stroop tasks with no feature repetitions to minimize priming-related effects. Moreover, Intelligence Quotient (IQ) and Cognitive Reserve (CR) were assessed. Older adults were impaired in verbal interference resolution (Stroop effect), but their verbal Stroop effect negatively correlated with verbal IQ. Moreover older adults\u2019 general performance speed was correlated with education and CR. Conversely, spatial interference resolution did not significantly differ between age groups. Nonetheless, we found that CR correlated with various aspects of task performance in the spatial domain: general accuracy and conflict resolution in both speed and accuracy. Our results are compatible with a compensatory role of IQ, CR and education on age-related deficits in information processing and conflict resolution. The nature and extent of this compensatory influence partially changes according to the domain