Changes in electrophysiological static and dynamic human brain functional architecture from childhood to late adulthood.

This magnetoencephalography study aimed at characterizing age-related changes in resting-state functional brain organization from mid-childhood to late adulthood. We investigated neuromagnetic brain activity at rest in 105 participants divided into three age groups: children (6-9 years), young adults (18-34 years) and healthy elders (53-78 years). The effects of age on static resting-state functional brain integration were assessed using band-limited power envelope correlation, whereas those on transient functional brain dynamics were disclosed using hidden Markov modeling of power envelope activity. Brain development from childhood to adulthood came with (1) a strengthening of functional integration within and between resting-state networks and (2) an increased temporal stability of transient (100-300 ms lifetime) and recurrent states of network activation or deactivation mainly encompassing lateral or medial associative neocortical areas. Healthy aging was characterized by decreased static resting-state functional integration and dynamic stability within the primary visual network. These results based on electrophysiological measurements free of neurovascular biases suggest that functional brain integration mainly evolves during brain development, with limited changes in healthy aging. These novel electrophysiological insights into human brain functional architecture across the lifespan pave the way for future clinical studies investigating how brain disorders affect brain development or healthy aging.

Plasma cytokines profile in older subjects with late onset Alzheimer's disease or vascular dementia.

Some cytokines have been involved in the pathogenesis of late onset Alzheimer's disease (LOAD). A possible increase in plasma cytokines levels has been reported in LOAD and vascular dementia (VD), but the results of previous studies are conflicting. We evaluated the plasma levels of IL-6, TNF-alpha, IL-1beta, and IL-10 in four groups of older individuals: 60 patients with LOAD, 80 patients with VD, 40 subjects with cerebrovascular disease but without dementia (CDND), and 42 controls (C). By analysis of covariance (adjustment for age, gender, coronary heart disease, diabetes, hypertension, smoking, and alcohol consumption) we found that: *IL-1beta was higher in VD, LOAD, and CDND compared with controls (p<0.005). *TNF-alpha was higher in VD and LOAD compared to C (p<0.05), and in VD compared to LOAD (p<0.03). *IL-6 was higher in VD compared with LOAD (p<0.03). No differences in IL-10 values were found (Kruskal-Wallis, Asymp. Sig. 0.14). By logistic regression analysis, we demonstrated that high levels (defined as above the median) of IL-1beta and TNF-alpha, but not of IL-6, were associated with increased likelihood of having VD and LOAD compared to C, while high IL-6 levels were associated with a increased probability of having VD, compared with LOAD. Our study support the notion of a low-grade systemic inflammation in older patients with LOAD or VD, characterized by an increase in plasma IL-1beta and TNF-alpha levels. The high IL-6 levels found in VD might be not a specific finding, as it might come from several conditions including atherosclerosis and related vascular risk factors, comorbidity, and frailty.

High interleukin-6 plasma levels are associated with functional impairment in older patients with vascular dementia.

In older individuals, inflammatory mechanisms have been linked to the pathogenesis of both dementia and functional impairment. In this cross-sectional study we have investigated the possible association between some markers of systemic inflammation and functional status, in a sample of one hundred and forty older demented patients including 60 patients with late onset Alzheimer's disease (LOAD) and 80 with vascular dementia (VD). Functional status was evaluated by Barthel Index (BI); the total score ranged from 0 (total dependency) to 20 (total autonomy). Interleukin-1beta, Tumor Necrosis Factor-alpha, Interleukin- 6, Interleukin- 8, and Transforming Grow Factor beta were quantified by ELISA. Among the cytokines evaluated, only IL-6 was correlated with the BI (r: -0.32, p < 0.001). The mean levels of IL-6 progressively decreased from I (9.50 pg/mL), to II (6.40 pg/mL), to III BI tertile (4.80 pg/mL) (p < 0.02). At multiple regression analysis, IL-6 was associated with BI in the whole sample and in VD, but not in LOAD, independent of age, gender, smoking, alcohol consumption, hypertension, diabetes, coronary heart disease, previous stroke, and mini mental state examination score. Our study suggests the existence of an independent and negative relationship between IL-6 plasma levels and functional status in older individuals with vascular dementia. This finding might contribute to explain the 'excess of disability' phenomenon described in older demented patients.

Leukoaraiosis is associated with functional impairment in older patients with Alzheimer's disease but not vascular dementia.

BACKGROUND: Leukoaraiosis (LA) is a common finding in older persons, and might be associated with reduced cognitive performance, gait abnormalities, and functional impairment. Although LA is more frequent in persons affected by dementia, scant data are available about its clinical consequences in this group of patients. OBJECTIVE: To study the association between presence of LA and functional performance in basic activities of daily living in a sample of older persons affected by dementia. DESIGN: We conducted a cross-sectional study on 214 patients; 77 affected by late onset Alzheimer's disease (LOAD), and 137 by vascular dementia (VD). Functional status was assessed using Barthel Index (BI). LA was assessed using computed tomography. RESULTS: In LOAD patients, LA (OR: 7.87; 1.26-48.94), and MMSE score (OR: 0.83; 0.71-0.98) were associated with the risk of severe disability, independent of age, gender, diabetes, hypertension, coronary heart disease, left ventricular hypertrophy, atrial fibrillation, and brain atrophy. In VD patients, MMSE score (OR: 0.77; 0.64-0.93), and CHD (OR: 7.41; 1.09-50.21), but not LA (OR: 2.07; 0.45-9.45) were associated with a severe functional impairment after multivariate adjustment. CONCLUSIONS: Our study suggests that LA might be associated with a worse functional status in basic activities of daily living in patients affected by LOAD but not VD. LA might act synergistically with cognitive and behavioural disturbances to the onset and progression of disability of these patients.

Aortico-right ventricular tunnel.

A successful operation on an infant with a tunnel through which the aorta communicated with the right ventricle is reported. The diagnosis was suspected preoperatively on the basis of two-dimensional Doppler color echocardiography and confirmed by cardiac catheterization. The aortico-right ventricular tunnel originated independently from the left coronary ostium and above the sinus of Valsalva. Patch closure from inside the tunnel under deep hypothermia was successfully performed. Follow-up is satisfactory 5 years later.