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With the aging of the global population, neurodegenerative diseases are emerging as a major public health issue. The adoption of a less sedentary lifestyle has been shown to have a beneficial effect on cognitive decline, but the molecular mechanisms responsible are less clear. Here we provide a detailed analysis of the complex molecular, cellular, and systemic mechanisms underlying age-related cognitive decline and how lifestyle choices influence these processes. A review of the evidence from animal models, human studies, and postmortem analyses emphasizes the importance of integrating physical exercise with cognitive, multisensory, and motor stimulation as part of a multifaceted approach to mitigating cognitive decline. We highlight the potential of these non-pharmacological interventions to address key aging hallmarks, such as genomic instability, telomere attrition, and neuroinflammation, and underscore the need for comprehensive and personalized strategies to promote cognitive resilience and healthy aging. [ABSTRACT FROM AUTHOR]

Cognitive abilities tend to decline with aging, with variation between individuals, and many studies seek to identify genetic biomarkers that more accurately anticipate risks related to pathological aging. We investigated the influence of BDNF, NTRK2, and FNDC5 single nucleotide polymorphisms (SNPs) on the cognitive performance of young and older adults with contrasting educational backgrounds. We addressed three questions: (1) Is education associated with reduced age-related cognitive decline? (2) Does the presence of SNPs explain the variation in cognitive performance observed late in life? (3) Is education differentially associated with cognition based on the presence of BDNF, NTRK2, or FNDC5 polymorphisms? We measured the cognitive functions of young and older participants, with lower and higher education, using specific and sensitive tests of the Cambridge Automated Neuropsychological Test Assessment Battery. A three-way ANOVA revealed that SNPs were associated with differential performances in executive functions, episodic memory, sustained attention, mental and motor response speed, and visual recognition memory and that higher educational levels improved the affected cognitive functions. The results revealed that distinct SNPs affect cognition late in life differentially, suggesting their utility as potential biomarkers and emphasizing the importance of cognitive stimulation that advanced education early in life provides. [ABSTRACT FROM AUTHOR]

• Automated and domain-specific tests are sensitive to discriminate cognitively healthy young and older adults. • Episodic memory (PAL) and working memory (SWM) tests are the most sensitive when analyzing a sample with a wide age range (older adults and young adults) and their assessment should be prioritized. • Episodic memory (PAL TEA) has a high discriminatory capacity on assessing older adults, suggesting that this test may have greater clinical potential. • Better education or to practice physical exercise are associated with greater cognitive performances, reinforcing its beneficial potential to successful cognitive trajectories in both the young and aging brain. Increased interindividual variability in cognitive performance during aging has been proposed as an indicator of cognitive reserve. To determine if interindividual variability performance in episodic memory (PAL), working memory (SWM), reaction time (RTI), and sustained attention (RVP) could differentiate clusters of differential cognitive performance in healthy young and older adults and search for cognitive tests that most contribute to these differential performances. We employed hierarchical cluster and canonical discriminant function analyses of cognitive scores using the Cambridge Neuropsychological Test Automated Battery (CANTAB) to identify cognitive variability in older and young adults using the coefficient of variability of cognitive performances between and within groups. We also analyzed potential influences of age, education, and physical activity. Cluster analysis distinguished groups with differential cognitive performance and correlation analysis revealed coefficient of variability and cognitive performance associations. The greater the coefficient of variability the poorer was cognitive performance in RTI but not in PAL and SWM. Older adults showed diverse trajectories of cognitive decline, and better education or higher percentage of physically active individuals exhibited better cognitive performance in both older and young adults. PAL and SWM are the most sensitive tests to investigate the wide age range encompassing older and young adults. In older adults' intragroup analysis PAL showed greater discriminatory capacity, indicating its potential for clinical applications late in life. Our data underscore the importance of studying variability as a tool for early detection of subtle cognitive declines and for interpreting results that deviate from normality. [ABSTRACT FROM AUTHOR]