Brain reserve, cognitive reserve, compensation, and maintenance: operationalization, validity, and mechanisms of cognitive resilience

Significant individual differences in the trajectories of cognitive aging and in age-related changes of brain structure and function have been reported in the past half-century. In some individuals, significant pathological changes in the brain are observed in conjunction with relatively well-preserved cognitive performance. Multiple constructs have been invoked to explain this paradox of resilience, including brain reserve, cognitive reserve, brain maintenance, and compensation. The aim of this session of the Cognitive Aging Summit III was to examine the overlap and distinctions in definitions and measurement of these constructs, to discuss their neural and behavioral correlates and to propose plausible mechanisms of individual cognitive resilience in the face of typical age-related neural declines

Long-term cardiovascular and cerebrovascular morbidity in Israeli thyroid cancer survivors

Objective: Thyroid cancer (TC) survivors may be at risk of subsequent cardiovascular and cerebrovascular (CaV&CeV) morbidity. The 2009 American Thyroid Association (ATA) guidelines recommended less aggressive treatment for low-risk TC patients. The aim of this study was to assess the atherosclerotic CaV&CeV outcome of Israeli TC survivors compared to individuals with no thyroid disease, and the atherosclerotic CaV&CeV outcome before (2000–2008) and after (2009–2011) implementation of the 2009 ATA guidelines. Methods: All members of the largest Israeli healthcare organization who were diagnosed with TC from 1/2000 to 12/2014 (study group) and age- and sex-matched members with no thyroid disease (controls) were included. Adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated using Cox proportional hazards models. Results: The mean follow-up was 7.6 ± 4.2 and 7.8 ± 4.1 years for the study (n = 5,677, 79% women) and control (n = 23,962) groups, respectively. The former had an increased risk of new atherosclerotic CaV&CeV events (adjusted HR 1.26, 95% CI 1.15–1.39). The 5-year incidence of CaV&CeV was lower (adjusted HR 0.49, 95% CI 0.38–0.62) from 2009 to 2011 compared to 2000 to 2008, but remained higher in the study group than in the control group (adjusted HR 1.5, 95% CI 1.14–1.69). Conclusions: This large Israeli population-based cohort study showed greater atherosclerotic CaV&CeV morbidity in TC survivors compared to individuals with no thyroid diseases. There was a trend toward a decreased 5-year incidence of atherosclerotic CaV&CeV events among TC survivors following the implementation of the 2009 ATA guidelines, but it remained higher compared to the general population

Neural traces of stress: cortisol related sustained enhancement of amygdala-hippocampal functional connectivity

Stressful experiences modulate neuro-circuitry function, and the temporal trajectory of these alterations, elapsing from early disturbances to late recovery, heavily influences resilience and vulnerability to stress. Such effects of stress may depend on processes that are engaged during resting-state, through active recollection of past experiences and anticipation of future events, all known to involve the default mode network (DMN). By inducing social stress and acquiring resting-state functional magnetic resonance imaging (fMRI) before stress, immediately following it, and 2 h later, we expanded the time-window for examining the trajectory of the stress response. Throughout the study repeated cortisol samplings and self-reports of stress levels were obtained from 51 healthy young males. Post-stress alterations were investigated by whole brain resting-state functional connectivity (rsFC) of two central hubs of the DMN: the posterior cingulate cortex (PCC) and hippocampus. Results indicate a ’recovery’ pattern of DMN connectivity, in which all alterations, ascribed to the intervening stress, returned to pre-stress levels. The only exception to this pattern was a stress-induced rise in amygdala-hippocampal connectivity, which was sustained for as long as 2 h following stress induction. Furthermore, this sustained enhancement of limbic connectivity was inversely correlated to individual stress-induced cortisol responsiveness (AUCi) and characterized only the group lacking such increased cortisol (i.e., non-responders). Our observations provide evidence of a prolonged post-stress response profile, characterized by both the comprehensive balance of most DMN functional connections and the distinct time and cortisol dependent ascent of intra-limbic connectivity. These novel insights into neuro-endocrine relations are another milestone in the ongoing search for individual markers in stress-related psychopathologies

Thyroid cysts: a new extra-adrenal site of aldosterone synthase expression and increased aldosterone content

Abstract Background The rapid re-accumulation of fluid following aspiration of thyroid cystic lesions suggests that active transport of sodium and water may be involved in volume regulation of these lesions. In this study we address the possibility that aldosterone may take part in this process. Subjects and methods Thirty-one patients (29 women and two men), with a mean age of 52·7 ± 13·2 years (range: 27-77 years) underwent evaluation for thyroid nodules that had a sonographic cystic component. Cystic fluid obtained by FNA biopsy was sent for cytological examination and biochemical measurements. In 10 patients, material was collected for RNA extraction and determination of aldosterone synthase expression by RT-PCR amplification. Results All lesions were benign, cystic, colloid nodules. Cyst fluid aldosterone levels as measured by routine radioimmunoassay (RIA) were elevated above the normal plasma levels in all but five patients. Mean aldosterone levels were 27·1 ± 22·9 ng /dl (SD) (range: 5·9-117·5 ng/dl). In contrast, cyst cortisol values were in the low, low normal serum range (6·2 ± 2·9 µ g/dl, range: 0·2-10·2 µ g/dl). Sodium, chloride and potassium levels were 137 ± 4·7 mEq/l, 98 ± 5 mEq/l and 4·9 ± 1·4 mEq/l, respectively. Plasma aldosterone levels were normal in all patients tested. To confirm these results, 12 samples were assayed after extraction and chromatography using a highly specific antibody. Cyst aldosterone levels in this group were elevated above the normal serum range in all but one patient (mean concentration: 24·5 ± 14·6 ng/dl, range: 8·72-40·1 ng /dl). In this group, 18(OH)B levels were within the normal plasma range (12-55 ng /dl) in all but one patient (34·9 ± 17 ng/dl). Furthermore, aldosterone synthase mRNA expression was found in aspirates of four of 10 patients. Conclusions The increased aldosterone concentration and the presence of aldosterone synthase expression suggest that aldosterone may be locally produced and secreted in thyroid tissue. The pathophysiological implications of this finding remain to be established

The Circadian Syndrome Is a Significant and Stronger Predictor for Cardiovascular Disease than the Metabolic Syndrome-The NHANES Survey during 2005-2016.

The study aimed to compare the predictive value of the Circadian Syndrome (CircS) and Metabolic Syndrome (MetS) for cardiovascular disease (CVD). We used data of 12,156 adults aged ≥20 years who attended National Health and Nutrition Examination Survey (NHANES) 2005-2016. Mortality was obtained from the registry updated to 2019. The CircS was defined based on components of the MetS, in addition to short sleep and depression. Both the MetS and CircS were directly associated with self-reported history of CVD. The odds ratios for prevalent CVD associated with the CircS and MetS, respectively, were 2.92 (95% confidence interval (CI) 2.21-3.86) and 3.20 (2.38-4.30) in men, and 3.27 (2.34-4.59) and 3.04 (2.15-4.30) in women. The CircS had a better predictive power for prevalent CVD than that of MetS, as indicated by the higher positive predictive value (PPV); in men, the PPV for prevalent CVD with CircS was 23.1% and with MetS 20.9%, and in women these were 17.9% vs. 16.4%, respectively. However, the PPV of the CircS and MetS did not differ for the CVD mortality prediction. Women with CircS alone had a higher risk for both prevalent CVD and CVD mortality than those with MetS alone. In conclusion, the CircS is a significant and stronger predictor for CVD than the MetS in US adults

Total serum cholinesterase activity predicts hemodynamic changes during exercise and associates with cardiac troponin detection in a sex-dependent manner.

BACKGROUND: Imbalanced autonomic nervous system (ANS) activity is associated with poor cardiovascular outcome. However, clinically validated biomarkers to assess parasympathetic function are not yet available. We sought to evaluate parasympathetic dysfunction by measuring serum cholinesterase activity and to determine its relationship to high sensitive cardiac troponin T (hs-cTnT) as well as traditional non-invasive parameters of ANS function during exercise in apparently healthy individuals. METHODS: We enrolled 1526 individuals (mean age 49 ± 11 yr., 75% men) from the Tel Aviv Medical Center Inflammation Survey (TAMCIS). We used the acetylcholine (ACh) analog acetylthiocholine (ATCh) as a substrate that is hydrolyzed by both ACh degrading enzymes and reflects the total serum capacity for acetylcholine hydrolysis, referred to as cholinergic status (CS). All subjects performed a cardiac stress test reviewed on the spot by a cardiologist and multiple physiological and metabolic parameters including hs-cTnT were measured. RESULTS: CS values at rest predicted multiple exercise-hemodynamic changes. Heart rate recovery after exercise was inversely correlated to CS values (p  5 ng/L) presented with elevated CS levels compared to women with undetectable levels; 1423 ± 272.5 vs 1347 ± 297.9 (p = 0.02). An opposite trend was observed in men. Metabolic dysfunction parameters were also associated with CS elevation in both men and women. CONCLUSIONS: Parasympathetic dysfunction assessed by total serum cholinesterase activity predicts hemodynamic changes during exercise. CS is also associated with hs-cTnT detection in women and inversely so in men. Future studies to assess the potential clinical use of this new sex-specific biomarker in cardiovascular disease risk stratification are warranted