Age-related differences in spatiotemporal markers of gait stability during dual task walking.

Increased stride-to-stride variability during walking characterizes gait instability and predicts falling in older adults. Walking while performing cognitive tasks (dual task walking) is also associated with increased risk of falling. The purpose of the study was to examine whether gait velocity and stride-to-stride variability in gait velocity differ in older adults compared with middle-aged and younger adults during normal and dual task walking conditions. Sixty older (n=20, mean age=81 years), middle-aged (n=20, mean age=48 years), and young adults (n=20, mean age=25 years) participated in the study. Gait parameters were quantified with GAITRite instrumentation. In the dual task condition, participants spelled five-letter words in reverse while walking across the walkway. Across groups, gait velocity was slower (p<0.001) and stride-to-stride variability in gait velocity was greater (p=0.001) in dual task walking. Older subjects walked more slowly than did middle-aged and younger subjects and the difference in gait velocity was greatest in the dual task condition (p<0.05). Variability in stride velocity was increased in older subjects compared with middle-aged and younger subjects (p<0.05). Additionally, in older subjects, impaired walking performance was associated with impaired cognitive performance in dual task walking. The gait changes observed in dual task walking characterize decreased gait stability and indicate that cognitively demanding tasks during walking have a destabilizing effect on gait and may place older people at a greater risk of falling.

Kallikrein cascades in traumatic spinal cord injury: in vitro evidence for roles in axonopathy and neuron degeneration.

Kallikreins (KLKs) are a family of 15 secreted serine proteases with emerging roles in neurologic diseases. To illuminate their contributions to the pathophysiology of spinal cord injury (SCI), we evaluated acute through chronic changes in the immunohistochemical appearance of 6 KLKs (KLK1, KLK5, KLK6, KLK7, KLK8, and KLK9) in postmortem human traumatic SCI cases, quantified their RNA expression levels in experimental murine SCI, and assessed the impact of recombinant forms of each enzyme toward murine cortical neurons in vitro. Temporally and spatially distinct changes in KLK expression were observed with partially overlapping patterns between human and murine SCI, including peak elevations (or reductions) during the acute and subacute periods. Kallikrein 9 showed the most marked changes and remained chronically elevated. Importantly, a subset of KLKs (KLK1, KLK5, KLK6, KLK7, and KLK9) were neurotoxic toward primary neurons in vitro. Kallikrein immunoreactivity was also observed in association with swollen axons and retraction bulbs in the human SCI cases examined. Together, these findings demonstrate that elevated levels of a significant subset of KLKs are positioned to contribute to neurodegenerative changes in cases of CNS trauma and disease and, therefore, represent new potential targets for the development of neuroprotective strategies.

Kallikreins are associated with secondary progressive multiple sclerosis and promote neurodegeneration.

Tissue kallikrein KLK1 and the kallikrein-related peptidases KLK2-15 are a subfamily of serine proteases that have defined or proposed roles in a range of central nervous system (CNS) and non-CNS pathologies. To further understand their potential activity in multiple sclerosis (MS), serum levels of KLK1, 6, 7, 8 and 10 were determined in 35 MS patients and 62 controls by quantitative fluorometric ELISA. Serum levels were then correlated with Expanded Disability Status Scale (EDSS) scores determined at the time of serological sampling or at last clinical follow-up. Serum levels of KLK1 and KLK6 were elevated in MS patients (p