Adiponectin (ADPN) is a plasma protein secreted by adipose tissue showing pleiotropic effects with anti-diabetic, anti-atherogenic, and anti-inflammatory properties. Initially, it was thought that the main role was only the metabolism control. Later, ADPN receptors were also found in the central nervous system (CNS). In fact, the receptors AdipoR1 and AdipoR2 are expressed in various areas of the brain, including the hypothalamus, hippocampus, and cortex. While AdipoR1 regulates insulin sensitivity through the activation of the AMP-activated protein kinase (AMPK) pathway, AdipoR2 stimulates the neural plasticity through the activation of the peroxisome proliferator-activated receptor alpha (PPARα) pathway that inhibits inflammation and oxidative stress. Overall, based on its central and peripheral actions, ADPN appears to have neuroprotective effects by reducing inflammatory markers, such as C-reactive protein (PCR), interleukin 6 (IL6), and Tumor Necrosis Factor a (TNFa). Conversely, high levels of inflammatory cascade factors appear to inhibit the production of ADPN, suggesting bidirectional modulation. In addition, ADPN appears to have insulin-sensitizing action. It is known that a reduction in insulin signaling is associated with cognitive impairment. Based on this, it is of great interest to investigate the mechanism of restoration of the insulin signal in the brain as an action of ADPN, because it is useful for testing a possible pharmacological treatment for the improvement of cognitive decline. Anyway, if ADPN regulates neuronal functioning and cognitive performances by the glycemic metabolic system remains poorly explored. Moreover, although the mechanism is still unclear, women compared to men have a doubled risk of developing cognitive decline. Several studies have also supported that during the menopausal transition, the estrogen reduction can adversely affect the brain, in particular, verbal memory and verbal fluency. During the postmenopausal period, in obese and insulin-resistant individuals, ADPN serum levels are significantly reduced. Our recent study has evaluated the relationship between plasma ADPN levels and cognitive performances in menopausal women. Thus, the aim of this review is to summarize both the mechanisms and the effects of ADPN in the central nervous system and the relationship between plasma ADPN levels and cognitive performances, also in menopausal women.

Background: In geriatric age, cognitive impairment and cardiovascular disorders are frequent comorbidities. Age-related anatomical and functional cardiac changes, including the autonomic system, could interfere with the control of different cognitive domains. Therefore, we assess the relationship between long-term heart rate variability (HRV), as a measure of autonomic nervous system (ANS) functioning, and cognitive performance in elderly patients representative of outpatients in a real-life setting. Methods: Of 155 elderly outpatients (aged >65 years) screened, 117 enrolled patients underwent anthropometric evaluation, cardiac assessment by 12-lead electrocardiogram, 24-h ECG recording, and blood pressure (BP) measurement, as well as global cognitive evaluation by a standardized multidimensional assessment, including the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment test (MoCA). HRV analysis was performed on 24-h ECG recordings focusing on time-domain indices [Standard deviation of the NN intervals (SDNN), standard deviations of 5-min mean values of the NN intervals for each 5-min interval (SDANN), and root mean squares of successive differences of the NN intervals (RMSSD)] and on frequency-domain measurements [heart rate (HR), low frequency (LF), high frequency (HF), and LF/HF]. Multivariate linear analysis was used to explore the influence of the HRV significant variables on MMSE and MoCA test values. Results: The MMSE and MoCA scores were both significantly and positively correlated with the sympathetic system parameters (SDNN, SDANN, LF, and LF/HF ratio), but not with the parasympathetic system parameters (RMSSD and HF). Multivariate analysis confirms this relationship. Conclusions: Our results show that, in a representative real-life community elderly population, an increased sympathetic activity, but not decreased vagal activity, is

Supplemental Digital Content is available in the text.