About 50% of Italian patients with ALS had some degree of cognitive impairment, in keeping with a previous Irish study, despite the largely different genetic background of the two populations. The lower educational attainment in patients with ALS-FTD indicated a possible role of cognitive reserve in ALS-related cognitive impairment. ALS-ECI and ALS-NECI may represent discrete cognitive syndromes in the continuum of ALS and FTD.

Background: Understanding the determinants of quality of life (QoL) in amyotrophic lateral sclerosis (ALS) has become increasingly important with the recent emphasis on the comprehensive management of patients. Objective: To evaluate the determinants of QoL in ALS using two scales with different theoretical constructs: the Schedule for the Evaluation of QoL-Direct Weighting (SEIQoL-DW), which evaluates subjective aspects of QoL, and the McGill QoL Questionnaire (MQOL), which evaluates both health related and non-health related factors of QoL. Methods: Eighty consecutive patients with ALS underwent a battery of tests evaluating QoL and a series of physical, emotional, psychological, and socioeconomic predictor variables. A stepwise linear regression model was used to compare QoL scores and explicatory variables. Results: SEIQoL-DW score was related to social support, depression, religiosity, and socioeconomic status. Total MQOL score was related to social support, socioeconomic status, and clinical status. MQOL single item score (MQOL-SIS) was related to social support, depression, social withdrawal, and socioeconomic status. SEIQoL-DW score was not related to total MQOL score. Conversely, a significant correlation was found between SEIQoL-DW and MQOL-SIS. Conclusions: With both QoL scales, the most important explicatory variable of QoL was the self perceived quality of social support. Physical status was not relevant in determining QoL. This study indicates that health related QoL measures are not adequate to assess QoL in patients with ALS, because their appreciation of QoL mainly relies on psychological, supportive, and spiritual factors. Therapeutic interventions should consider the psychological needs of patients and pay greater attention to caregivers' issues.

This large FDG PET investigation provided unprecedented evidence of relatively increased metabolism in the amygdalae, midbrain and pons in ALS patients as compared with control subjects, possibly due to local activation of astrocytes and microglia. Highly significant relative decreases in metabolism were found in large frontal and parietal regions in the bulbar onset patients as compared with the spinal onset patients and the controls, suggesting a differential metabolic and neuropsychological state between the two conditions.

Neurobehavioral symptoms were present in 50% of our ALS patients and were related to bulbar symptoms. They have a profound negative impact on caregivers' psychological status and were highly related with caregivers' burden.

ALS patients with the C9ORF72 hexanucleotide repeat expansion had a more widespread central nervous system involvement than ALS patients without genetic mutations, with or without comorbid FTD, consistent with their more severe clinical picture.