Age-associated leukoaraiosis and cortical cholinergic deafferentation

Bohnen, Nicolaas I.; Müller, Martijn; Kuwabara, Hiroto; Constantine, Gregory; Studenski, Stephanie A.

doi:10.1212/wnl.0b013e3181a187c6

Cited by 53 publications

(50 citation statements)

References 32 publications

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“…43,44 Furthermore, the burden of wMLs around the frontal ventricular horns may be of particular importance, given the potential to disrupt several important subcortical afferent and cortical efferent projections. 45 …”

Section: Imaging White Matter Lesionsmentioning

confidence: 99%

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White matter lesions in Parkinson disease

2011

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Pure vascular parkinsonism without evidence of nigral Lewy body pathology may occur as a distinct clinicopathological entity, but a much more frequent occurrence is the comorbid presence of age-associated white matter lesions (WMLs) in idiopathic Parkinson disease (PD). WMLs are associated with motor and cognitive symptoms in otherwise normal elderly individuals. Comorbid WMLs are, therefore, expected to contribute to clinical symptoms in PD. Studies of WMLs in PD differ with regard to methods of assessment of WML burden and the patient populations selected for analysis, but converging evidence suggests that postural stability and gait motor functions are predominantly affected. WMLs are described to contribute to dementia in Alzheimer disease, and emerging but inconclusive evidence indicates similar effects in PD. In this article, we review the literature addressing the occurrence and impact of WMLs in PD, and suggest that WMLs may exacerbate or contribute to some motor and cognitive deficits associated with PD. We review existing and emerging methods for studying white matter pathology in vivo, and propose future research directions.

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Section: Imaging White Matter Lesionsmentioning

confidence: 99%

“…wMLs of the deep frontal lobe could result in cortical cholinergic deafferentation and related cognitive impairment in elderly individuals without PD. 45 …”

Section: White Matter Lesions In Pdmentioning

confidence: 99%

White matter lesions in Parkinson disease

2011

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“…WMH partially identify underlying white matter pathology and may be associated with widespread white matter changes, the novel concept of white matter hyperintensities penumbra [107]. Disruption of fiber tracts in the developing brain could result in cortical cholinergic and monoaminergic deafferentation and impact attention, emotion and goal-directed behavior [99]. The characterization of WMH in young urbanites is critical and knowledge about the complex modulation of cytokines and chemokines in the setting of air pollution are important because they may shed light into the etiopathogenesis of well-characterized risk factors for neurodegeneration, vascular, and cognitive disorders and disability [106, 107].…”

Section: Compensatory Responses Versus Neurotoxic and Neurodegenermentioning

confidence: 99%

Early Alzheimer’s and Parkinson’s Disease Pathology in Urban Children: Friend versus Foe Responses—It Is Time to Face the Evidence

Calderón‐Garcidueñas

Franco-Lira

Mora-Tiscareño

et al. 2013

BioMed Research International

106

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Chronic exposure to particulate matter air pollution is known to cause inflammation leading to respiratory- and cardiovascular-related sickness and death. Mexico City Metropolitan Area children exhibit an early brain imbalance in genes involved in oxidative stress, inflammation, and innate and adaptive immune responses. Early dysregulated neuroinflammation, brain microvascular damage, production of potent vasoconstrictors, and perturbations in the integrity of the neurovascular unit likely contribute to progressive neurodegenerative processes. The accumulation of misfolded proteins coincides with the anatomical distribution observed in the early stages of both Alzheimer's and Parkinson's diseases. We contend misfolding of hyperphosphorylated tau (HPπ), alpha-synuclein, and beta-amyloid could represent a compensatory early protective response to the sustained systemic and brain inflammation. However, we favor the view that the chronic systemic and brain dysregulated inflammation and the diffuse vascular damage contribute to the establishment of neurodegenerative processes with childhood clinical manifestations. Friend turns Foe early; therefore, implementation of neuroprotective measures to ameliorate or stop the inflammatory and neurodegenerative processes is warranted in exposed children. Epidemiological, cognitive, structural, and functional neuroimaging and mechanistic studies into the association between air pollution exposures and the development of neuroinflammation and neurodegeneration in children are of pressing importance for public health.

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“…Currently, PET studies with [ 11 C]MP4A/P have also been used to evaluate AChE inhibition by pharmaceuticals in human and animals . Although [ 11 C]MP4A/P appeared to be an accomplished PET probe, the mechanism for the retention of its metabolites at the sites in the brain regions where they were generated remains unclear.…”

Section: Evaluation Of [11c]mp4a and [11c]mp4pmentioning

confidence: 99%

“…Many compounds labeled with 11 C and 18 F have been synthesized as candidate PET probes for the imaging of cerebral AChE, and several of these candidates have been used as radioprobes not only for cerebral AChE imaging in patients with neurological disorders but also for measuring the effects of AChE inhibitors . In this review, we will focus on the development of radioprobes for cerebral AChE imaging by PET.…”

Section: Introductionmentioning

confidence: 99%

PET probes for imaging brain acetylcholinesterase

Kikuchi¹,

Okamura²,

Zhang³

et al. 2013

Labelled Comp Radiopharmac

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Imaging acetylcholinesterase (AChE) is valuable not only for diagnosing and understanding dementia but also for monitoring the effects of cholinesterase inhibitors used as antidementia drugs and for determining the appropriate clinical dosage of newly developed cholinesterase inhibitors. The distribution of AChE in the living brain can be imaged with two different types of radioprobes, including substrate-type and ligand-type probes. The substrate-type positron emission tomography (PET) probes, N-[(11) C]methylpiperidin-4-yl acetate ([(11) C]MP4A), and its propionate, [(11) C]MP4P, have been widely used in clinical studies of dementia, including Alzheimer's disease. [(11) C]MP4A and [(11) C]MP4P have been used to demonstrate a reduction in AChE activity in the brains of dementia patients, as well as the bioavailability of AChE inhibitors, leading to the subsequent development of the widely available (18) F-labeled derivatives of MP4A. In addition, several radiolabeled cholinesterase inhibitors have been developed as PET probes for AChE mapping in the brain. Herein, we have reviewed the development of PET probes for the imaging of AChE in the brain and described the principles of measuring AChE activity in the brain using PET with substrate-type radioprobes. A discussion of the reagents developed from substrate-type PET probes for the specific measurement of AChE activity in vitro has also been provided.

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Age-associated leukoaraiosis and cortical cholinergic deafferentation

Abstract: Objective: To investigate the relationship between age-associated MRI leukoaraiosis or white matter hyperintensities (WMH) and cortical acetylcholinesterase (AChE) activity.

Cited by 53 publications

References 32 publications

White matter lesions in Parkinson disease

White matter lesions in Parkinson disease

Early Alzheimer’s and Parkinson’s Disease Pathology in Urban Children: Friend versus Foe Responses—It Is Time to Face the Evidence

PET probes for imaging brain acetylcholinesterase

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