The relationship between oestrogen and executive functioning in ALS females with emerging Frontotemporal Lobar Degeneration (FTLD) supports a neuroendocrine model of FTLD attenuation

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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. Findings: 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.

Original languageEnglish (US)
Pages (from-to)74-85
Number of pages12
JournalAmyotrophic Lateral Sclerosis and Frontotemporal Degeneration
Volume18
Issue number1-2
DOIs
StatePublished - Jan 2 2017

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Frontotemporal Lobar Degeneration
Estrogens
Dementia
Consensus
Extremities

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology

Cite this

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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. Findings: 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.",
author = "{for the VALUES Consortium} and Claire Flaherty and J. Kraft and A. Brothers and Marissa Harrison and Richard Legro and Andrea Manni and C. Yang and Zachary Simmons",
year = "2017",
month = "1",
day = "2",
doi = "10.1080/21678421.2016.1249487",
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T1 - The relationship between oestrogen and executive functioning in ALS females with emerging Frontotemporal Lobar Degeneration (FTLD) supports a neuroendocrine model of FTLD attenuation

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AU - Flaherty, Claire

AU - Kraft, J.

AU - Brothers, A.

AU - Harrison, Marissa

AU - Legro, Richard

AU - Manni, Andrea

AU - Yang, C.

AU - Simmons, Zachary

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N2 - 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. Findings: 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.

AB - 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. Findings: 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.

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