Study On Cognitive Function Of Amyotrophic Lateral Sclerosis

Part 1. Cognitive impairment in Chinese patients with sporadic amyotrophic lateral sclerosisBackground:It has reached a consensus that patients with amyotrophic lateral sclerosis (ALS) could display cognitive impairment characterized by executive dysfunction or even dementia, but cognitive spectrum of Chinese patients with ALS still waits to be documented.Methods:A total of 106 incident patients with sporadic ALS were enrolled and comprehensive neuropsychological tests covering memory, executive function, attention, language, visuospatial function were administered to them. Neuropsychological performances of 76 age-and education-matched healthy controls were used for the purpose of classification and comparison.Results:106 patients were categorized into 4 subtypes:84(79.2%) ALS with normal cognition (ALS-NC),12(11.3%) ALS with executive cognitive impairment (ALS-ECI), 5(4.7%) ALS with non-executive cognitive impairment (ALS-NECI), and 5(4.7%) ALS with frontotemporal lobe degeneration (ALS-FTLD). Under the same criteria,2(2.6%) and 1(1.3%) healthy controls were diagnosed as ECI and NECI, respectively. The proportion of ECI was significantly higher in non-demented ALS than that in healthy controls, but it was not for NECI. Patients with ALS-FTLD had significantly severer bulbar function and older age than those with ALS-NC.Conclusion:Comorbid FTLD occurred in around 5% of Chinese sporadic ALS cases. Different genetic background and unique age distribution of Chinese ALS patients might be the reasons for the relatively low rate of comorbid FTLD. Cognitive dysfunction, predominant but not exclusive in executive area, was present in around 16% of ALS patients.Part 2. Relationship among onset type, neuropsychology and FDG-PET brain metabolic change in amyotrophic lateral sclerosisBackground:Amyotrophic lateral sclerosis (ALS) belongs to neurodegenerative diseases of central nervous system, however, researches about cortex of ALS turned to insufficient. FDG-PET is a sensitive tool to reflect abnormal cortical metabolism, which is appropriate to evaluate patients with ALS.Methods:25 patients with ALS were included into this study and they underwent comprehensive cognitive assessment, behavior and mood evaluation. Then FDG-PET was performed to all of them. They were divided into bulbar onset group (B-ALS) and spinal onset group (S-ALS) based on their onset type. We analyzed the differences between these 2 groups.Results:8 patients belonged to B-ALS while the other 17 were S-ALS. B-ALS performed poorer than S-ALS in many neuropsychological tests, however, these differences did not reach statistical significance. Disinhibitive behavior score of B-ALS was significantly higher than that of S-ALS. Brain metabolism was significantly lower in several frontal and temporal areas in B-ALS than those in S-ALS.Conclusion:B-ALS was severer in the aspect of cognitive impairment and abnormal behaviors, which were in accordance with changes in brain metabolic imaging. These findings supported the theory that bulbar neurons had extensive connection with cortex, and that ALS is a heterogeneous disease.Part 3. Clinical, neuroimaging and genetic profiles of amyotrophic lateral sclerosis with frontotemporal lobe degenerationBackground:Comorbid frontotemporal lobe degeneration (FTLD) appeared to be rare in the context of Chinese patients with amyotrophic lateral sclerosis (ALS).Methods:Patients with FTLD and other types of neurodegenerative dementia were physically examined in detail and electromyography was performed to those with suspected dysarthria, limb atrophy or weakness. Cognitive and behavioral screenings were performed to all ALS patients. Patients with ALS-FTLD entered further analysis of neuroimaging and genetics.Result:Among the 12 patients diagnosed as ALS-FTLD,5 patients began with personality change or amnesia, while diseases in the remaining 7 cases began with limb weakness or dysarthria. Dementia type of 10 cases was behavioral variant FTLD (bvFTD), and the remaining 2 cases were diagnosed as semantic dementia (SD) and dementia, respectively. Electromyography of all 12 patients showed diffuse neurogenic changes. Constructional neuroimaging of 10 patients showed cerebral atrophy predominantly in frontal and temporal lobes. FDG-PET was conducted in 5 patients, indicating hypometabolism mainly in frontal and/or temporal lobes. NeuroQ analysis revealed that bilateral frontal lobes were the most hypometabolic areas for ALS-FTLD. Among 8 patients who underwent genetic screening,1 patient was C9ORF72 mutation earners.Conclusion:bvFTD is the major type of dementia in the context of ALS. Metabolic neuroimaging could assist accurate diagnosis, and it revealed that bilateral frontal lobes were the most hypometabolic areas for ALS-FTLD. C9ORF72 gene was an important pathogenic mutation for ALS-FTLD, although it was rare in Chinese population.