Major depressive disorder (MDD) is a severe mental illness that affects 5-20% of the general population. Current antidepressant drugs exert only a partial clinical efficacy because approximately 30% of depressed patients failed to respond to these drugs and antidepressants produce remission only in 30% of patients. This can be explained by the fact that the complex pathophysiology of depression has not been completely elucidated, and treatments have been mainly developed following the "monoaminergic hypothesis" of depression without considering the key role of other factors involved in the pathogenesis of MDD, such as the role of chronic stress and neuroinflammation. Chronic stress acts as a risk factor for the development of MDD through the impairment of neurotrophins signaling such as brain-derived neurotrophic factor (BDNF) and transforming-growth-factor-β1 (TGF-β1). Stress-induced depressive pathology contributes to altered BDNF level and function in MDD patients and, thereby, an impairment of neuroplasticity at the regional and circuit level. Recent studies demonstrate that aerobic exercise strongly increases BDNF production and it may contribute as a non-pharmacological strategy to improve the treatment of cognitive and affective symptoms in MDD. Here we will provide a general overview on the possible synergism between physical activity and antidepressants in MDD. Physical activity can synergize with antidepressant treatment by rescuing neurotrophins signaling in MDD patients, promoting neuronal health and recovery of function in MDD-related circuits, finally enhancing pharmacotherapeutic response. This synergism might be particularly relevant in elderly patients with late-life depression, a clinical subgroup with an increased risk to develop dementia.

Apathy is a neuropsychiatric symptom observed in different neurological and psychiatric disorders. Although apathy is considered a symptom, it has been recently reconsidered as a syndrome characterised by three dimensions: cognitive symptoms, affective symptoms and behavioural symptoms. Recent studies have shown that apathy can be considered as a prodromal symptom of Alzheimer’s disease (AD), but also an indicator of the transition from mild cognitive impairment to AD. According to this scenario, an early detection of apathy in subjects with Mild Cognitive Impairment (MCI) and Mild AD can be a valid psychometric strategy to improve an early diagnosis and promote a prompt intervention. The Apathy Evaluation Scale is a validated tool composed of 18 items that assess and quantify emotional, behavioural and cognitive aspects of apathy. The aim of this study is to assess the specific reliability and validity of the Italian version of the Apathy Evaluation Scale—Clinician Version (AES-C) to detect apathy both in amnestic MCI and mild AD patients. In the present paper, we therefore examined the psychometric properties and the invariance of the Italian Version of the AES-C conducted on a sample composed of an experimental group of amnestic MCI and AD patients (N = 107) and a control group (N = 107) constituted by Age- and Sex-matched healthy controls. Results confirm the goodness of the scale. Confirmatory factory analysis confirmed that the AES-C Italian Version presents the same stability of one second-order factor and three first-order factors identified in the original version, and all items are predicted by a single general factor. Moreover, the scale was found to be invariant across both populations. Moreover, reliability and discriminant analysis showed good values. We found in the experimental group a negative correlation between the AES-C and Frontal Assessment Battery (FAB) (rs = −0.21, p < 0.001) and Mini Mental State Examination (MMSE) (rs = −0.04, p < 0.001), while a positive correlation was found between the AES-C and Hamilton psychiatric Rating scale for Depression (HAM-D) scores (rs = 0.58, p < 0.001) Overall, our data demonstrated the validity of the Italian version of the AES-C for the assessment of apathy both in MCI and in AD patients.