ABSTRACT
BACKGROUND AND PURPOSE: The aim of the study was to evaluate the metabolic correlates of Apolipoprotein E (APOE) genotype in amyotrophic lateral sclerosis (ALS) and to investigate the role of ε2 as a risk factor for cognitive impairment. METHODS: A total of 159 ALS cases underwent APOE and ALS-related genes analysis, neuropsychological assessment and cerebral 18 F-2-fluoro-2-deoxy-D-glucose positron emission tomography. The APOE genotype was regressed against whole brain metabolism as assessed by 18 F-2-fluoro-2-deoxy-D-glucose positron emission tomography, with age, sex, education, type of onset and C9orf72 status as covariates. RESULTS: Brain metabolism was significantly positively correlated with APOE genotype from ε2/ε2 to ε3/ε4 in the left prefrontal [Brodmann area (BA) 10], orbitofrontal (BAs 11, 45, 47) and anterior cingulate (BA 32) cortices. There was a tendency to a relative hypometabolism going towards the ε2/ε2 extreme. CONCLUSIONS: We found a highly significant, relatively lower metabolism in association with the ε2 allele in extra-motor areas typically affected in frontotemporal dementia (left prefrontal, orbitofrontal and anterior cingulate cortices), strengthening the finding of a role of ε2 as a risk factor for cognitive impairment in ALS. Our data suggested a link between cholesterol homeostasis and neurodegeneration.
Subject(s)
Amyotrophic Lateral Sclerosis/genetics , Apolipoproteins E/genetics , Brain/metabolism , Genotype , Adult , Aged , Alleles , Amyotrophic Lateral Sclerosis/diagnostic imaging , Amyotrophic Lateral Sclerosis/metabolism , Brain/diagnostic imaging , Female , Glucose/metabolism , Humans , Male , Middle Aged , Positron-Emission Tomography , Risk FactorsABSTRACT
OBJECTIVE: To evaluate the frequency of neurobehavioral symptoms related to FTLD in a consecutive series of amyotrophic lateral sclerosis (ALS) patients and to assess their influence on patients' and caregivers' mood, burden, and quality of life. METHODS: A total of 70 couples of ALS patients and their caregivers consecutively seen in our ALS clinic were separately interviewed using a battery of tests assessing frontotemporal-related neurobehavioral symptoms, emotional status, and quality of life. Patients' behavioral abnormalities were assessed with the Frontal Systems Behavior Scale (FrSBe). Caregiver burden was assessed with the Caregiver Burden Inventory (CBI). RESULTS: According to caregivers' evaluations, 34 (48.6%) patients had FrSBe pathological scores at the time of the interview. According to patients' evaluation, 9 (12.9%) patients had pathological scores at the time of the interview. In caregivers' assessment, at the time of the interview the most commonly impaired neurobehavioral domain was apathy (39 patients, 55.7%), followed by executive dysfunction (32, 45.7%) and disinhibition (18, 25.7%). Neurobehavioral symptoms were related to the presence of bulbar symptoms at the time of the interview, but not to patients' age, gender, or physical status (ALS-FRS score). Patients' neurobehavioral symptoms were significantly related to lower caregivers' quality of life, highest depression, and highest burden, both in univariate and in multivariable analyses. CONCLUSIONS: 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.
