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The fit of the second model was also good (��2 test = 105.1, d.f. = 58, p = 0.0002, RMSEA = 0.027, CFI = 1.000, TLI = 1.000). The relationship between the slope for depression and the slope for rejection of care was significant (a = 0.828, SE = 0.138, p [http://www.selleckchem.com/products/Staurosporine.html http://www.selleckchem.com/products/Staurosporine.html] cannot conclude that the relationship between depression and behaviors directed towards others is mediated by rejection of care. Since we did not observe changes [http://www.selleckchem.com/products/dorsomorphin-2hcl.html Dorsomorphin mouse] in psychosis and pain, we did not consider mediation models for these processes. Discussion The results of this longitudinal study showed that changes in lack of understanding or depression commonly precede changes in rejection of care. Changes in behaviors directed towards others are related to changes in lack of understanding, depression and rejection of care. Furthermore, a mediation model suggested that the relationship between lack of understanding and behaviors directed towards others was mediated by rejection of care. Therefore, our results support conclusions of our previous cross-sectional study [13], which found that lack of understanding and depression are the two main risk factors for development of rejection of care and behaviors directed towards others. However, our results are more informative because longitudinal models provide more information regarding temporal relationships between the variables, [http://en.wikipedia.org/wiki/Resminostat Resminostat] and the mediation model provides information about the order in which the symptoms develop. Initial psychotic symptoms and pain were also related to increased rejection of care, but we did not observe changes in the number of psychotic symptoms and pain within our study period. Regarding to the absence of observed changes in pain, Hendriks et al. [23] found a high proportion of patients with pain persistence. That precluded inclusion of psychotic symptoms and pain in the mediation model. A relationship of depression to resistive behavior (rejection of care) and aggression (abusive symptoms) was already reported by Lyketsos et al. [24] and by Leonard et al. [25]. They found, in agreement with our results, that psychotic symptoms play a minor role in the development of these behaviors. The lack of understanding is caused by the progression of dementia, and it increases the prevalence of rejection of care [26]; this increase in rejection of care contributes to the increasing behaviors directed towards others. It may be improved by communication skills training of professionals and family caregivers that includes verbal skills, nonverbal and emotional skills, behavioral management skills, usage of tools and theoretical knowledge [27].