Central cholinergic presbyvestibulopathy network changes and imbalance in Parkinson's disease and older persons

帕金森病和老年人中枢性胆碱能性老年前庭病网络的变化和失衡

基本信息

项目摘要

Abstract The management of dopamine resistant postural instability and gait difficulties (PIGD) features, such as falls, represents perhaps the most important unmet clinical need in persons with Parkinson's disease (PD) and is a major cause for reduced quality of life. The loss of functional abilities and quality of life associated with the emergence of PIGD is further compromised by coinciding emergence of cognitive decline and dementia. This may reflect progressive non-dopaminergic pathologies, such as cholinergic system changes. Vestibular impairment, in particular more chronic bilateral vestibular dysfunction of older age (defined as presbyvestibulopathy, PVP), is a significant contributor to imbalance and falls in older US adults. Unlike acute vestibular disorders that are sporadic, PVP is also common in an age-associated disorder like PD. We have novel preliminary data showing that the presence of PVP in PD is associated with imbalance independent from nigrostriatal dopaminergic losses. Using a data-driven whole brain selection method of vesicular acetylcholine transporter (VAChT) [18F]FEOBV PET brain regions, we also found that the presence of PVP in PD is associated with cholinergic system changes most prominently in the medial geniculate nucleus (MGN) and by medial temporal lobe structures involved in multimodal sensory processing, spatial orientation and navigation. Lower cholinergic binding in the MGN and a composite measure of cholinergic binding in PVP-related specific brain regions associated with presence of imbalance in people with PD. Given recent recognition of important vestibular information processing functions of the MGN, our data suggest that this small metathalamic nucleus may function as a key node in the central vestibular neural network. These observations in people with PD may also be relevant for non-PD older adults with PVP. Cholinergic and dopaminergic losses not only occur in PD but are also part of normal aging starting from young adulthood on. We have preliminary data showing that age-associated vulnerability of cholinergic nerve terminal losses is most conspicuous in the MGN and mesiotemporal lobe. This suggests that cholinergic vulnerability of normal aging may contribute to the relationship between PVP and cholinergic system changes in PD. Conversely, age-associated vulnerability in these structures may explain the high and increasing prevalence of PVP in non-PD older persons. We propose to perform brain cholinergic [18F]FEOBV and dopamine transporter [11C]PE2I PET imaging and balance assessment and vestibular testing in persons with PD and non-PD older adults. The overarching goal of this study is to test the hypothesis that brain region-specific cholinergic system changes associate with the presence of both PVP and fall status in persons with PD independent of dopaminergic losses. We also propose to test the secondary hypothesis that age-associated cholinergic vulnerability in the MGN and mediotemporal lobe associate with the presence of both PVP and fall status in non-PD older adults independent of dopaminergic losses of normal aging.
摘要

项目成果

期刊论文数量(0)
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Nicolaas Ida Bohnen其他文献

Nicolaas Ida Bohnen的其他文献

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{{ truncateString('Nicolaas Ida Bohnen', 18)}}的其他基金

Core B: Clinical Resource Core
核心 B:临床资源核心
  • 批准号:
    10493236
  • 财政年份:
    2021
  • 资助金额:
    $ 61.04万
  • 项目类别:
Project I: Evolution of cholinergic deficits within multisensory, cognitive, and motor integration brain regions and development of PIGD features in PwP
项目 I:多感觉、认知和运动整合脑区胆碱能缺陷的演变以及 PwP 中 PIGD 特征的发展
  • 批准号:
    10282005
  • 财政年份:
    2021
  • 资助金额:
    $ 61.04万
  • 项目类别:
Vestibulopathy, imbalance and gait disturbances in Parkinson disease
帕金森病的前庭病、失衡和步态障碍
  • 批准号:
    10396478
  • 财政年份:
    2021
  • 资助金额:
    $ 61.04万
  • 项目类别:
Core B: Clinical Resource Core
核心 B:临床资源核心
  • 批准号:
    10282002
  • 财政年份:
    2021
  • 资助金额:
    $ 61.04万
  • 项目类别:
Vestibulopathy, imbalance and gait disturbances in Parkinson disease
帕金森病的前庭病、失衡和步态障碍
  • 批准号:
    10179754
  • 财政年份:
    2021
  • 资助金额:
    $ 61.04万
  • 项目类别:
Core B: Clinical Resource Core
核心 B:临床资源核心
  • 批准号:
    10672408
  • 财政年份:
    2021
  • 资助金额:
    $ 61.04万
  • 项目类别:
Central cholinergic presbyvestibulopathy network changes and imbalance in Parkinson's disease and older persons
帕金森病和老年人中枢性胆碱能性老年前庭病网络的变化和失衡
  • 批准号:
    10663385
  • 财政年份:
    2021
  • 资助金额:
    $ 61.04万
  • 项目类别:
Project I: Evolution of cholinergic deficits within multisensory, cognitive, and motor integration brain regions and development of PIGD features in PwP
项目 I:多感觉、认知和运动整合脑区胆碱能缺陷的演变以及 PwP 中 PIGD 特征的发展
  • 批准号:
    10672414
  • 财政年份:
    2021
  • 资助金额:
    $ 61.04万
  • 项目类别:
Project I: Evolution of cholinergic deficits within multisensory, cognitive, and motor integration brain regions and development of PIGD features in PwP
项目 I:多感觉、认知和运动整合脑区胆碱能缺陷的演变以及 PwP 中 PIGD 特征的发展
  • 批准号:
    10493260
  • 财政年份:
    2021
  • 资助金额:
    $ 61.04万
  • 项目类别:
Vestibulopathy, imbalance and gait disturbances in Parkinson disease
帕金森病的前庭病、失衡和步态障碍
  • 批准号:
    10627784
  • 财政年份:
    2021
  • 资助金额:
    $ 61.04万
  • 项目类别:

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