1997; Strong et al 1999; Lomen-Hoerth et al 2003;

1997; Strong et al. 1999; Lomen-Hoerth et al. 2003; Schreiber et al. 2005; Ogawa et al. 2009). Although increased cognitive impairment in bulbar-onset patients is frequently described, other studies have failed in finding a link between bulbar-onset and cognitive decline (Kew et al. 1993; Mantovan et al. 2003; Ringholz et al. 2005; Rippon et al. 2006). In conclusion, these composite studies show that a significant subgroup of ALS patients exhibit cognitive

deficits affecting frontal lobe functioning, specifically in planning, attention, and verbal, and nonverbal fluency. There is also minor involvement in memory and language skills, which could be due Inhibitors,research,lifescience,medical in part to frontal dysfunction. The level of abnormality ranges from overt dementia, meeting criteria for FTD, to subtle impairments detected only by neuropsychological Inhibitors,research,lifescience,medical testing. The neuroimaging studies in nondemented ALS patients strongly indicate an organic basis to the frontal deficits detected on neuropsychological testing and a task force to further detect nonmotor changes in ALS has been created (Tsermentseli et al. 2012). Longitudinal studies With regard to the progression Inhibitors,research,lifescience,medical of the cognitive decline in ALS, the current opinion is that the cognitive impairment slowly declines over the course of the

disease. Strong et al. (1999) found a progression over time of the cognitive deficits across several

domains, including working memory, problem solving, mental flexibility, recognition Inhibitors,research,lifescience,medical memory for words and faces, and visual-perceptual skills in five patients with bulbar-onset ALS, while limb-onset ALS patients showed no decline at the six months follow-up. A MR spectroscopy following the neuropsychological testing demonstrated a significant neuronal loss in the anterior cingulate gyrus in bulbar patients that was evident early in the course of cognitive impairment and correlated with the PD0332991 appearance Inhibitors,research,lifescience,medical of impaired cognition. Another longitudinal study noted that cognitive deficits were present at initial testing and, after the early decline, seemed to remain stable over time in contrast to motor decline; in addition, bulbar-onset patients performed worst in many neuropsychological tests than spinal-onset (-)-p-Bromotetramisole Oxalate ones and this subgroup difference increased on follow-up (Schreiber et al. 2005). These findings were replicated by another longitudinal study (Abrahams et al. 2005) in which selective deficits in spoken and written verbal fluency did not show deterioration over a six months period in a group of nondemented ALS patients. In a study by Robinson et al. (2006), no significant and meaningful between-group and within-group differences in cognitive function were found over time.

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