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Sex and gender-biological and social constructs-significantly impact the prevalence of protective and risk factors, influencing the burden of Alzheimer's disease (AD; amyloid beta and tau) and other pathologies (e.g., cerebrovascular disease) which ultimately shape cognitive trajectories. Understanding the interplay of these factors is central to understanding resilience and resistance mechanisms explaining maintained cognitive function and reduced pathology accumulation in aging and AD. In this narrative review, the ADDRESS! Special Interest Group (Alzheimer's Association) adopted a multidisciplinary approach to provide the foundations and recommendations for future research into sex- and gender-specific drivers of resilience, including a sex/gender-oriented review of risk factors, genetics, AD and non-AD pathologies, brain structure and function, and animal research. We urge the field to adopt a sex/gender-aware approach to resilience to advance our understanding of the intricate interplay of biological and social determinants and consider sex/gender-specific resilience throughout disease stages. HIGHLIGHTS: Sex differences in resilience to cognitive decline vary by age and cognitive status. Initial evidence supports sex-specific distinctions in brain pathology. Findings suggest sex differences in the impact of pathology on cognition. There is a sex-specific change in resilience in the transition to clinical stages. Gender and sex factors warrant study: modifiable, immune, inflammatory, and vascular.
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Unlike vitamin K antagonists (VKAs), the new oral anticoagulants (NOACs)-direct thrombin inhibitor, dabigatran, and direct activated factor X inhibitors, rivaroxaban, and apixaban-do not require routine INR monitoring. Compared to VKAs, they possess relatively rapid onset of action and short halflives, but vary in relative degrees of renal excretion as well as interaction with p-glycoprotein membrane transporters and liver cytochrome P450 metabolic enzymes. Recent completed phase III trials comparing NOACs with VKAs for stroke prevention in atrial fibrillation (AF)-the RE-LY, ROCKET AF, and ARISTOTLE trials-demonstrated at least noninferior efficacy, largely driven by significant reductions in haemorrhagic stroke. Major and nonmajor clinically relevant bleeding rates were acceptable compared to VKAs. Of note, the NOACs caused significantly less intracranial haemorrhagic events compared to VKAs, the mechanisms of which are not completely clear. With convenient fixed-dose administration, the NOACs facilitate anticoagulant management in AF in the community, which has hitherto been grossly underutilised. Guidelines should evolve towards simplicity in anticipation of greater use of NOACs among primary care physicians. At the same time, the need for caution with their use in patients with severely impaired renal function should be emphasised.
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<p><b>INTRODUCTION</b>Several randomised controlled trials have demonstrated better outcomes with primary percutaneous coronary intervention (PCI) over fibrinolytic therapy in the treatment of patients with ST-segment elevation myocardial infarction (STEMI) and normal renal function. Whether this benefit extends to patients with impaired renal function is uncertain.</p><p><b>MATERIALS AND METHODS</b>We studied 1672 patients with STEMI within 12 hours of symptom onset who were admitted to 2 major public hospitals in Singapore from 2000 to 2002. All patients received either upfront fibrinolytic or PCI as determined by the attending cardiologist. Serum creatinine was measured on admission and the glomerular filtration rate (GFR) was determined using the Modification of Diet in Renal Disease equation. The impact of reperfusion strategy on 30-ay mortality was then determined for patients with GFR > or =60 mL min-(1) 1.73 m-(2) and GFR <60 mL min-(1) 1.73 m-(2).</p><p><b>RESULTS</b>The mean age was 56 +/- 12 years (85% male) and mean GFR was 81 +/- 30 mL min-(1) 1.73 m-(2). Unadjusted 30-day mortality rates for fibrinolytic-treated vs primary PCI-treated patients were 29.4% vs 17.9%, P <0.05, in the impaired renal function group and 5.4% vs 3.1%, P <0.05, in the normal renal function group. After adjusting for covariates, primary PCI was associated with a significantly lower mortality in the normal renal function group [odds ratio (OR), 0.41; 95% confidence interval (CI), 0.19-0.89] but not in the impaired renal function group [OR, 0.70; 95% CI, 0.31-1.60].</p><p><b>CONCLUSIONS</b>Primary PCI was associated with improved 30-day survival among patients with normal renal function but not among those with impaired renal function. Randomised trials are needed to study the relative efficacy of both reperfusion strategies in patients with impaired renal function.</p>
