title: The relationship between oestrogen and executive functioning in ALS females with emerging Frontotemporal Lobar Degeneration (FTLD) supports a neuroendocrine model of FTLD attenuation.
abstract: OBJECTIVE
  The prevalence of ALS cognitive or behavioural impairment (ci or bi) consistent with Frontotemporal Degeneration (FTLD) approachs 50%, while ∼5-10% progress to dementia. Our goal was to explore ci and bi differencs between bulbar and limb onset, as well as the neuroprotective potential of oestrogen in emerging FTLD.
  
  
  METHODS
  We applied Mann Whitney U to evaluate differences in cognitive and behavioural profiles between site of onset in 78 female and 83 male non-demented ALS participants classified by current consensus criteria with ci. For females, we also examined differences by oestrogen level.
  
  
  RESULTS
  Between group analyses found significantly worse Letter Fluency (LF) for bulbar onset, and worse Category Fluency (CF) for bulbar females. Significantly worse performance was found for low oestrogen females for LF and Similarities, with significantly worse LF for low oestrogen bulbar onset. No significant differences were found for behavioural subgroups, while moderate-severe range traits were higher in occurrence for bulbar and low oestrogen bulbar onset.
  
  
  CONCLUSIONS
  Findings support our previously published mesocortical pathway associated "bottom-up" model of FTLD emergence in ALSbi, extending it with a hierarchal hypothesis involving ascending cerebellar pathways in ALSci and ALSbi, further suggesting a role for oestrogen in mitigating female FTLD progression.
authors.affiliation: a Department of Neurology , Penn State College of Medicine , Hershey , PA , USA.
authors.forename: C
authors.initials: C
authors.lastname: Flaherty
authors.affiliation: b Department of Psychology , Penn State University , Middletown , PA , USA.
authors.forename: J
authors.initials: J
authors.lastname: Kraft
authors.affiliation: c Department of Human Development and Family Studies , Colorado State University , Fort Collins , CO , USA.
authors.forename: A
authors.initials: A
authors.lastname: Brothers
authors.affiliation: b Department of Psychology , Penn State University , Middletown , PA , USA.
authors.forename: M
authors.initials: M
authors.lastname: Harrison
authors.affiliation: d Department of OB/GYN , Penn State College of Medicine , Hershey , PA , USA.
authors.forename: R S
authors.initials: RS
authors.lastname: Legro
authors.affiliation: e Division of Endocrinology, Diabetes and Metabolism , Penn State College of Medicine , Hershey , PA , USA , and.
authors.forename: A
authors.initials: A
authors.lastname: Manni
authors.affiliation: f Department of Public Health Sciences , Penn State College of Medicine , Hershey , PA , USA.
authors.forename: C
authors.initials: C
authors.lastname: Yang
authors.affiliation: a Department of Neurology , Penn State College of Medicine , Hershey , PA , USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Simmons
mesh_terms: D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000150:complications / Q000453:epidemiology; D017028:Caregivers / Q000523:psychology; D003072:Cognition Disorders / Q000209:etiology* / Q000378:metabolism; D018450:Disease Progression; D004967:Estrogens / Q000378:metabolism*; D056344:Executive Function / Q000502:physiology*; D005260:Female; D057174:Frontotemporal Lobar Degeneration / Q000150:complications / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D012727:Sex Characteristics
chemical_list: D004967:Estrogens
keywords: Frontotemporal lobar degeneration; amyotrophic lateral sclerosis; behavioural decline; cognitive decline; executive functioning; gender; oestrogen