Stokin, Gorazd B.

Background: Considering the world’s rapidly increasing life expectancy, with people working and maintaining active lifestyles longer than ever before, addressing the effects of aging on cognition is of utmost importance. A greater understanding of cognitive aging may also be critical in distinguishing natural cognitive aging from pre-clinical stages of Alzheimer’s disease and related cognitive disorders. Objective: To systematically examine the association between aging and cognitive performance in a cognitively and otherwise healthy probability population-based sample using a computer-based method. Methods: This cross-sectional study enrolled 673 cognitively and otherwise healthy participants aged 25–89 years (mean age 52.3±14.2 years, 52.5% of whom were female) from the Kardiovize study cohort. Mild cognitive impairment and dementia cases were excluded, followed by measurement of cognitive performance with the computer-administered Cogstate Brief Battery. We used ANCOVA and Modified Signed-Likelihood Ratio tests to examine patterns of cognition across age groups. Results: We found a gradual decrease in cognitive performance across the lifespan, which required two decades to demonstrate significant changes. In contrast to attention and learning, psychomotor speed and working memory showed the most significant age-related decrease and variability in performance. The established pattern of cognitive aging was not altered by sex or education. Conclusion: These findings corroborate, validate, and extend the current understanding of natural cognitive aging and pinpoint specific cognitive domains with the most extensive age-related interindividual differences. This will contribute to the development of strategies to preserve cognition with aging and may also serve to improve early diagnostics of cognitive disorders using computer-based methods.

Abstract Introduction We examined the association between cerebrospinal fluid (CSF)‐derived biomarkers of Alzheimer's disease and neuropsychiatric symptoms (NPS) in older non‐demented adults. Methods We included 784 persons (699 cognitively unimpaired, 85 with mild cognitive impairment) aged ≥ 50 years who underwent CSF amyloid beta (Aβ42), hyperphosphorylated tau 181 (p‐tau), and total tau (t‐tau) as well as NPS assessment using Beck Depression and Anxiety Inventories (BDI‐II, BAI), and Neuropsychiatric Inventory Questionnaire (NPI‐Q). Results Lower CSF Aβ42, and higher t‐tau/Aβ42 and p‐tau/Aβ42 ratios were associated with BDI‐II and BAI total scores, clinical depression (BDI‐II ≥ 13), and clinical anxiety (BAI ≥ 10), as well as NPI‐Q–assessed anxiety, apathy, and nighttime behavior. Discussion CSF Aβ42, t‐tau/Aβ42, and p‐tau/Aβ42 ratios were associated with NPS in community‐dwelling individuals free of dementia. If confirmed by a longitudinal cohort study, the findings have clinical relevance of taking into account the NPS status of individuals with abnormal CSF biomarkers.

Abstract We here posit that measurements of midlife cognition can be instructive in understanding cognitive disorders. Even though molecular events signal possible onset of cognitive disorders decades prior to their clinical diagnoses, cognition and its possible early changes in midlife remain poorly understood. We characterize midlife cognition in a cognitively healthy population‐based sample using the Cogstate Brief Battery and test for associations with cardiovascular, adiposity‐related, lifestyle‐associated, and psychosocial variables. Learning and working memory showed significant variability and vulnerability to psychosocial influences in midlife. Furthermore, midlife aging significantly and progressively increased prevalence of suboptimal cognitive performance. Our findings suggest that physiological changes in cognition, measured with simple tests suitable for use in everyday clinical setting, may signal already in midlife the first clinical manifestations of the presymptomatic biologically defined cognitive disorders. This pilot study calls for longitudinal studies investigating midlife cognition to identify clinical correlates of biologically defined cognitive disorders.

Abstract Introduction We investigated the longitudinal relationship between cortical amyloid deposition, anxiety, and depression and the risk of incident mild cognitive impairment (MCI). Methods We followed 1440 community‐dwelling, cognitively unimpaired individuals aged ≥ 50 years for a median of 5.5 years. Clinical anxiety and depression were assessed using Beck Anxiety and Depression Inventories (BAI, BDI‐II). Cortical amyloid beta (Aβ) was measured by Pittsburgh compound B positron emission tomography (PiB‐PET) and elevated deposition (PiB+) was defined as standardized uptake value ratio ≥ 1.48. We calculated Cox proportional hazards models with age as the time scale, adjusted for sex, education, and medical comorbidity. Results Cortical Aβ deposition (PiB+) independent of anxiety (BAI ≥ 10) or depression (BDI‐II ≥ 13) increased the risk of MCI. There was a significant additive interaction between PiB+ and anxiety (joint effect hazard ratio 6.77; 95% confidence interval 3.58–12.79; P = .031) that is, being PiB+ and having anxiety further amplified the risk of MCI. Discussion Anxiety modified the association between PiB+ and incident MCI.

Ideal cardiovascular health (CVH) is defined for the presence of ideal behavioral and health metrics known to prevent cardiovascular disease (CVD). The association of circulatory phospho- and sphingo-lipids to primary reduction in cardiovascular risk is unclear. Our aim was to determine the association of CVH metrics with the circulating lipid profile of a population-based cohort. Serum sphingolipid and phospholipid species were extracted from 461 patients of the randomly selected prospective Kardiovize study based on Brno, Czech Republic. Lipids species were measured by a hyphenated mass spectrometry technique, and were associated with poor CVH scores, as defined by the American Heart Association. Phosphatidylcholine (PC), phosphatidylethanolamine (PE), lysophosphatidylcholine (LPC), lysophosphatidylethanolamine (LPE) species were significantly lower in ideal and intermediate scores of health dietary metric, blood pressure, total cholesterol and blood fasting glucose compared to poor scores. Current smokers presented higher levels of PC, PE and LPE individual species compared to non-smokers. Ceramide (Cer) d18:1/14:0 was altered in poor blood pressure, total cholesterol and fasting blood glucose metrics. Poor cardiovascular health metric is associated with a specific phospho- and sphingolipid pattern. Circulatory lipid profiling is a potential biomarker to refine cardiovascular health status in primary prevention strategies.

Background There is wide variability in cardiac rehabilitation (CR) dose (ie, number of sessions) delivered, and no evidence‐based recommendations regarding what dose to prescribe. We aimed to test what CR dose impacts major adverse cardiovascular events (MACEs). Methods and Results This is an historical cohort study of all patients who had coronary artery disease and who initiated supervised CR between 2002 and 2012 from a single major CR center. CR dose was defined as number of visits including exercise and patient education. Follow‐up was performed using record linkage from the Rochester Epidemiology Project. MACEs included acute myocardial infarction, unstable angina, ventricular arrhythmias, stroke, revascularization, or all‐cause mortality. Dose was analyzed in several ways, including tertiles, categories, and as a continuous variable. Cox models were adjusted for factors associated with dose and MACE. The cohort consisted of 2345 patients, who attended a mean of 12.5±11.1 of 36 prescribed sessions. After a mean follow‐up of 6 years, 695 (29.65%) patients had a MACE, including 231 who died. CR dose was inversely associated with MACE (hazard ratio, 0.66 [95% CI]; 0.55–0.91) in those completing ≥20 sessions, when compared with those not exposed to formal exercise sessions (≤1 session; log‐rank P =0.007). We did not find evidence of nonlinearity ( P ≥0.050), suggesting no minimal threshold nor ceiling. Each additional session was associated with a lower rate of MACE (fully adjusted hazard ratio, 0.98 [95% CI, 0.97–0.99]). Greater session frequency was also associated with lower MACE risk (fully adjusted hazard ratio, 0.74 [95% CI, 0.58–0.94]). Conclusions CR reduces MACEs, but the benefit appears to be linear, with greater risk reduction with higher doses, and no upper threshold.

In contrast to the decreasing burden related to cardiovascular disease (CVD), the burden related to dysglycemia and adiposity complications is increasing in Czechia, and local drivers must be identified. A comprehensive literature review was performed to evaluate biological, behavioral, and environmental drivers of dysglycemia and abnormal adiposity in Czechia. Additionally, the structure of the Czech healthcare system was described. The prevalence of obesity in men and diabetes in both sexes has been increasing over the past 30 years. Possible reasons include the Eastern European eating pattern, high prevalence of physical inactivity and health illiteracy, education, and income-related health inequalities. Despite the advanced healthcare system based on the compulsory insurance model with free-for-service healthcare and a wide range of health-promoting initiatives, more effective strategies to tackle the adiposity/dysglycemia are needed. In conclusion, the disease burden related to dysglycemia and adiposity in Czechia remains high but is not translated into greater CVD. This discordant relationship likely depends more on other factors, such as improvements in dyslipidemia and hypertension control. A reconceptualization of abnormal adiposity and dysglycemia into a more actionable cardiometabolic-based chronic disease model is needed to improve the approach to these conditions. This review can serve as a platform to investigate causal mechanisms and secure effective management of cardiometabolic-based chronic disease.

Alzheimer’s disease (AD) is a neurodegenerative disease associated with human aging. Ten percent of individuals over 65 years have AD and its prevalence continues to rise with increasing age. There are currently no effective disease modifying treatments for AD, resulting in increasingly large socioeconomic and personal costs. Increasing age is associated with an increase in low-grade chronic inflammation (inflammaging) that may contribute to the neurodegenerative process in AD. Although the exact mechanisms remain unclear, aberrant elevation of reactive oxygen and nitrogen species (RONS) levels from several endogenous and exogenous processes in the brain may not only affect cell signaling, but also trigger cellular senescence, inflammation, and pyroptosis. Moreover, a compromised immune privilege of the brain that allows the infiltration of peripheral immune cells and infectious agents may play a role. Additionally, meta-inflammation as well as gut microbiota dysbiosis may drive the neuroinflammatory process. Considering that inflammatory/immune pathways are dysregulated in parallel with cognitive dysfunction in AD, elucidating the relationship between the central nervous system and the immune system may facilitate the development of a safe and effective therapy for AD. We discuss some current ideas on processes in inflammaging that appear to drive the neurodegenerative process in AD and summarize details on a few immunomodulatory strategies being developed to selectively target the detrimental aspects of neuroinflammation without affecting defense mechanisms against pathogens and tissue damage.

Abstract Aims/Hypothesis The need for understanding obesity as a chronic disease, its stigmatization, and the lack of actionability related to it demands a new approach. The adiposity‐based chronic disease (ABCD) model is based on adiposity amount, distribution, and function, with a three stage complication‐centric rather than a body mass index (BMI)‐centric approach. The prevalence rates and associated risk factors are presented. Methods In total, 2159 participants were randomly selected from Czechia. ABCD was established as BMI ≥ 25 kg/m 2 or high body fat percent, or abdominal obesity and then categorized by their adiposity‐based complications: Stage 0: none; Stage 1: mild/moderate; Stage 2: severe. Results ABCD prevalence was 62.8%. Stage 0 was 2.3%; Stage 1 was 31.4%; Stage 2 was 29.1%. Comparing with other classifiers, participants in Stage 2 were more likely to have diabetes, hypertension, and metabolic syndrome than those with overweight, obesity, abdominal obesity, and increased fat mass. ABCD showed the highest sensitivity and specificity to detect participants with peripheral artery disease, increased intima media, and vascular disease. Conclusion/Interpretation The ABCD model provides a more sensitive approach that facilitates the early detection and stratification of participants at risk compared to traditional classifiers.