Divided attention markedly impairs the ability of patients with AD to regulate the stride-to-stride variations in gait timing. This susceptibility to distraction and its effect on stride time variability, a measure of gait unsteadiness, could partially explain the predilection to falling observed in patients with dementia. The results also support the concept that persons with AD have significant impairments in the cognitive domain of attention and that locomotor function relies upon cognitive, especially executive, function.

Alzheimer’s disease (AD) is generally understood as primarily affecting cognition while sparing motor function, at least until the later stages of the disease. Studies reported over the past 10 years, however, have documented a prevalence of falls in AD patients significantly higher than in age-matched normal elders; also persons with AD have been observed to have different walking patterns with characteristics that increase gait instability. Recent work in cognitive neuroscience has begun to demonstrate the necessity of intact cognition, particularly executive function, for competent motor control. We put the pieces of this puzzle together and review the current state of knowledge about gait and cognition in general along with an exploration of the association between dementia, gait impairment and falls in AD. We also briefly examine the current treatment of gait instability in AD, mainly exercise, and propose a new approach targeting cognition.

Serum response factor (SRF), a member of the MCM1, agamous, deficiens, SRF (MADS) family of transcriptional activators, has been implicated in the transcriptional control of a number of cardiac muscle genes, including cardiac alpha-actin, skeletal alpha-actin, alpha-myosin heavy chain (alpha-MHC), and beta-MHC. To better understand the in vivo role of SRF in regulating genes responsible for maintenance of cardiac function, we sought to test the hypothesis that increased cardiac-specific SRF expression might be associated with altered cardiac morphology and function. We generated transgenic mice with cardiac-specific overexpression of the human SRF gene. The transgenic mice developed cardiomyopathy and exhibited increased heart weight-to-body weight ratio, increased heart weight, and four-chamber dilation. Histological examination revealed cardiomyocyte hypertrophy, collagen deposition, and interstitial fibrosis. SRF overexpression altered the expression of SRF-regulated genes and resulted in cardiac muscle dysfunction. Our results demonstrate that sustained overexpression of SRF, in the absence of other stimuli, is sufficient to induce cardiac change and suggest that SRF is likely to be one of the downstream effectors of the signaling pathways involved in mediating cardiac hypertrophy.