Dementias are responsible for the most frequent neurodegenerative diseases and the seventh leading cause of death worldwide. As a result, there is a growing effort by the neuroscientific community to understand the physiopathology of neurodegenerative diseases, including how to alleviate the effects of the cognitive decline by means of non-pharmacological therapies (e.g., physical exercise). Studies have shown that exercise can improve aspects of brain health related to cognition. However, there still needs to be more knowledge regarding the mechanisms controlling these relationships, and a newly discovered cleansing system in the brain, named the glymphatic system, can be the missing link in this mechanism. The objective of this paper is to review recent findings regarding the potential impacts of physical exercise on the glymphatic system and its implications for the onset of neurodegenerative diseases. Additionally, considering the close interplay between exercise and sleep quality, we aim to explore how sleep patterns may intersect with exercise-induced effects on glymphatic function, further elucidating the complex relationship between lifestyle factors and brain health.

Systematically review randomized controlled trials on the efficacy of cognitive training on executive functions in healthy older people. The outcome measures were related to inhibitory control, working memory, and cognitive flexibility. Thirty-one trials were included in the systematic review and thirteen trials in the meta-analysis. In the overall analysis, the cognitive training enhanced inhibitory control when measured by the Stroop task (p < .001, d = 1.64) and working memory when measured by the Corsi Block task (p = .002, d = .16). A marginal significance was found for working memory in the Digit Span task - Forward (p = .06, d = .92). However, cognitive training did not enhance inhibitory control when measured by the Go/No-Go task (p = .76, d = .59), working memory when measured by the Digit Span - Backward (p = .72, d = .95) and N-Back (p = .10, d = .26) tasks, and cognitive flexibility when measured by Trail Making - Part B (p = .08, d = .27) and Semantic Fluency (p = .49, d = .06) tasks. Mixed evidence was found for inhibitory control and working memory; cognitive flexibility showed no evidence of improvement.

Objective: To evaluate the impact of a multicomponent physical exercise program on clinical variables associated with the glymphatic clearance system, sleep-awake patterns, and cognitive function in individuals with mild cognitive impairment or mild Alzheimer’s disease. Methods: This is a single-center parallel randomized controlled trial involving pre- and post-intervention assessments. The intervention consists of a 12 (±3)-week multicomponent aerobic and resistance physical exercise program of moderate intensity divided into 2 groups: an experimental group (undergoing multicomponent training) and a control group (no intervention). Eligible participants are those diagnosed with probable mild cognitive impairment or mild Alzheimer’s disease. Expected results: Anticipated outcomes suggest that the multicomponent training protocol, incorporating both aerobic and resistance physical exercises at a moderate intensity, will yield improvements in glymphatic clearance dynamics, sleep-awake parameters, and performance on cognitive, functional, and behavioral tasks among eligible patients. Relevance: The need to move beyond cognitive clinical testing justifies our trial, which proposes an assessment employing neuroimaging techniques and the analysis of biomarkers present in cerebrospinal fluid in conjunction with clinical tests for physical and cognitive assessment.

The glymphatic system has been proposed as a brain-wide pathway that promotes the exchange between cerebrospinal and interstitial fluids and facilitates the clearance of metabolic waste products, including amyloid-β and tau proteins. Diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) has emerged as a non-invasive magnetic resonance imaging technique proposed to indirectly assess glymphatic-related fluid dynamics. This systematic review evaluated the methodological consistency and clinical applicability of the ALPS index in neurodegenerative diseases. A structured search of PubMed (MEDLINE) and Web of Science identified human studies published up to January 2026 investigating DTI-ALPS in neurodegenerative conditions. Data regarding study populations, MRI acquisition parameters, image-processing methods, statistical approaches, and clinical associations were extracted and synthesized. Ten studies met the inclusion criteria. Across studies, lower ALPS index values were generally associated with cognitive impairment, amyloid burden, and disease severity, particularly in Alzheimer’s disease. Several studies incorporated multimodal biomarkers, including amyloid positron emission tomography and cerebrospinal fluid markers, thereby improving the biological interpretation of DTI-ALPS findings. However, substantial methodological heterogeneity was identified across studies, including variability in region-of-interest placement, diffusion acquisition protocols, and image-processing pipelines. Furthermore, the interpretation of diffusivity metrics as direct measures of glymphatic flow remains controversial. Current evidence suggests that DTI-ALPS may represent a promising non-invasive imaging marker of glymphatic-related alterations; however, its biological specificity and clinical applicability remain insufficiently established. Standardized acquisition protocols, harmonized analytical pipelines, and longitudinal multicenter studies are required to clarify its role in neurodegenerative disease research.

Unintentional weight loss in older adults is linked to multiple factors, being most often associated with comorbidities such as cancer, dementia syndromes, chronic obstructive pulmonary disease, and chronic kidney disease. Difficulty in managing this condition can quickly lead to malnutrition and, consequently, a state of cachexia. There is a dearth of studies in the literature regarding pharmacotherapeutic interventions for this population, with megestrol acetate (MA) being the most commonly studied medication. In this systematic review, we evaluated the use of MA to improve appetite and treat unintentional weight loss and/or the anorexia-cachexia syndrome in older adults. Randomized studies published up to December 2023 in three languages (Portuguese, Spanish, or English) were retrieved from five databases. We included 25 studies, most of which addressed the use of MA for treatment of patients diagnosed with cancer and the anorexia-cachexia syndrome. We used the PEDro scale to assess methodological quality of the included studies and calculated measures of heterogeneity, such as the tau-squared (τ2 ), I-squared (I2 ), and Q test, to assess consistency across studies. Although the studies selected for the systematic review suggest that patients with the anorexia-cachexia syndrome secondary to cancer may benefit from MA therapy, a meta-analysis of 8 selected studies (total n = 592) did not confirm this effect (p = 0.104). The indication of MA for treatment of patients with weight loss required further studies with better methodological designs to evaluate the efficacy and safety profile of this medication in older adults.