Daniele D. Urso, United Kingdom
King's College London Institute of Psychiatry, Psychology & NeuroscienceAuthor Of 3 Presentations
INCREASED BASAL FOREBRAIN VOLUMES ARE ASSOCIATED WITH FAVOURABLE COGNITIVE PROGRESSION IN LRRK2 PARKINSON’S DISEASE
Abstract
Aims
There is increasing evidence showing that LRRK2 mutations are associated with a milder clinical phenotype and preserved cholinergic function in Parkinson’s disease (PD). The basal forebrain (BF) is a dominantly cortically-projecting cholinergic area of the brain. In this study we aimed to assess whether BF volumes change in LRRK2 carriers with and without PD as well as their association with longitudinal cognitive functions.
Methods
Thirty-two symptomatic LRRK2-PD patients and 13 asymptomatic LRRK2 individuals were included from the Parkinson's Progression Markers Initiative. In addition, 32 patients with idiopathic PD (iPD) and 13 healthy controls matched to the previous groups were included. BF and other gray matter volumes were extracted from baseline T1-weighted MRI scans using previously established procedures. We compared BF volumes between groups and assessed their relationship with longitudinal cognitive changes using linear mixed effects models. Finally, mediation analyses assessed whether BF volumes mediated differences in cognitive trajectories between LRRK2-PD and iPD.
Results
LRRK2-PD patients showed significantly higher BF volumes compared to iPD (p=0.019) as did asymptomatic LRRK2 subjects compared to controls (p=0.008). No other brain regions showed increased volumes in LRRK2-PD and asymptomatic LRRK2. BF volumes predicted longitudinal decline in several cognitive functions in iPD patients but not in LRRK2-PD, who did not show cognitive changes over time. BF volumes significantly mediated the different cognitive trajectories between iPD and LRRK2-PD patients (bootstrap 95% CI 0.056-2.955).
Conclusions
Mutations in LRRK2 are associated with increased BF volumes, potentially reflecting a compensatory hypercholinergic state that could prevent cognitive decline in LRRK2-PD patients.
NEUROFILAMENT LIGHT PREDICTS WORSE NONMOTOR SYMPTOMS, DEPRESSION AND ANXIETY IN PARKINSON’S DISEASE
Abstract
Aims
The relationship between neurofilament light (NfL) and the burden of non-motor symptoms (NMS) in Parkinson’s disease (PD) is unclear. The aim of this study is to investigate whether NfL levels are associated with worsening NMS burden in PD.
Methods
Baseline and longitudinal NfL levels were measured in the cerebrospinal fluid (CSF) and serum in a large cohort of PD patients and healthy controls from the Parkinson’s Progression Marker Initiative. NMS were assessed using composite measures from the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) part I, the Geriatric Depression Scale (GDS) and the State-Trait Anxiety Inventory (STAI). We compared CSF and serum NfL between patients and controls and assessed their relationship with baseline and longitudinal NMS with correlations or linear mixed effects models. In all analyses, NfL levels were adjusted for potential confounders.
Results
Serum NfL levels were higher at baseline (p=0.043) and showed significant longitudinal increases (p<0.001) in PD patients compared to controls. Baseline and longitudinal serum and CSF NfL predicted worse MDS-UPDRS-I and depression (GDS) scores over time in PD (p<0.01). Furthermore, longitudinal changes in serum and CSF NfL were associated with worse longitudinal anxiety (STAI) scores in PD (p<0.05). These results were similar after adjusting for cognitive and motor deficits.
Conclusions
Our findings suggest that serum NfL levels are elevated in PD and that both serum and CSF NfL are associated with worse NMS. Serum NfL could potentially be used in the clinic as a non-invasive marker of NMS progression for PD patients.
LIVE DISCUSSION
Presenter of 2 Presentations
NEUROFILAMENT LIGHT PREDICTS WORSE NONMOTOR SYMPTOMS, DEPRESSION AND ANXIETY IN PARKINSON’S DISEASE
Abstract
Aims
The relationship between neurofilament light (NfL) and the burden of non-motor symptoms (NMS) in Parkinson’s disease (PD) is unclear. The aim of this study is to investigate whether NfL levels are associated with worsening NMS burden in PD.
Methods
Baseline and longitudinal NfL levels were measured in the cerebrospinal fluid (CSF) and serum in a large cohort of PD patients and healthy controls from the Parkinson’s Progression Marker Initiative. NMS were assessed using composite measures from the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) part I, the Geriatric Depression Scale (GDS) and the State-Trait Anxiety Inventory (STAI). We compared CSF and serum NfL between patients and controls and assessed their relationship with baseline and longitudinal NMS with correlations or linear mixed effects models. In all analyses, NfL levels were adjusted for potential confounders.
Results
Serum NfL levels were higher at baseline (p=0.043) and showed significant longitudinal increases (p<0.001) in PD patients compared to controls. Baseline and longitudinal serum and CSF NfL predicted worse MDS-UPDRS-I and depression (GDS) scores over time in PD (p<0.01). Furthermore, longitudinal changes in serum and CSF NfL were associated with worse longitudinal anxiety (STAI) scores in PD (p<0.05). These results were similar after adjusting for cognitive and motor deficits.
Conclusions
Our findings suggest that serum NfL levels are elevated in PD and that both serum and CSF NfL are associated with worse NMS. Serum NfL could potentially be used in the clinic as a non-invasive marker of NMS progression for PD patients.
LIVE DISCUSSION