Use of Cholinesterase Inhibitors in Non-Alzheimer’s Dementias

Noufi, Paul; Khoury, Rita; Jeyakumar, Sajeeka; Grossberg, George T.

doi:10.1007/s40266-019-00685-6

Cited by 36 publications

(23 citation statements)

References 101 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The analyses presented here are hypothesis generating and serve the purpose of informing the design of a confirmatory placebocontrolled trial which is now planned. The group sizes in the analyses comparing exposure-dependent differences at the 8 mg/day dose are small (46-62 with high exposure against 28-31 with low exposure), although comparable with other studies conducted in bvFTD [14][15][16][17][18][19]. The fact that there are consistent exposure-dependent differences achieving nominal significance on a range of clinical and MRI outcomes based on relatively small numbers of subjects suggests that the effects, if confirmed, are likely to be clinically meaningful.…”

Section: Discussionsupporting

confidence: 72%

See 1 more Smart Citation

Concentration-Dependent Activity of Hydromethylthionine on Clinical Decline and Brain Atrophy in a Randomized Controlled Trial in Behavioral Variant Frontotemporal Dementia

Shiells

Schelter

Bentham

et al. 2020

JAD

View full text Add to dashboard Cite

show abstract

Section: Discussionsupporting

confidence: 72%

“…There are no treatments licensed for any form of FTD. There is no reliable evidence of benefit for acetylcholinesterase inhibitors [14,15] and some suggestion that they may make FTD symptoms worse [16,17]. Memantine is better tolerated but is also ineffective [18,19].…”

Section: Introductionmentioning

confidence: 99%

Concentration-Dependent Activity of Hydromethylthionine on Clinical Decline and Brain Atrophy in a Randomized Controlled Trial in Behavioral Variant Frontotemporal Dementia

Shiells

Schelter

Bentham

et al. 2020

JAD

View full text Add to dashboard Cite

show abstract

“…Nonetheless, donepezil has been shown to afford some cognitive benefits for patients with VaD, while galantamine might have therapeutic utility in mixed dementia, AD, and VaD. IAChE use may even be considered in FTD if cognitive and behavioral symptoms are severe [130].…”

Section: Pharmacotherapy Of Dementia Diseases Andmentioning

confidence: 99%

Molecular Factors Mediating Neural Cell Plasticity Changes in Dementia Brain Diseases

Kozubski

Ong²,

Waleszczyk

et al. 2021

Neural Plasticity

View full text Add to dashboard Cite

Neural plasticity—the ability to alter a neuronal response to environmental stimuli—is an important factor in learning and memory. Short-term synaptic plasticity and long-term synaptic plasticity, including long-term potentiation and long-term depression, are the most-characterized models of learning and memory at the molecular and cellular level. These processes are often disrupted by neurodegeneration-induced dementias. Alzheimer’s disease (AD) accounts for 50% of cases of dementia. Vascular dementia (VaD), Parkinson’s disease dementia (PDD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD) constitute much of the remaining cases. While vascular lesions are the principal cause of VaD, neurodegenerative processes have been established as etiological agents of many dementia diseases. Chief among such processes is the deposition of pathological protein aggregates in vivo including β-amyloid deposition in AD, the formation of neurofibrillary tangles in AD and FTD, and the accumulation of Lewy bodies composed of α-synuclein aggregates in DLB and PDD. The main symptoms of dementia are cognitive decline and memory and learning impairment. Nonetheless, accurate diagnoses of neurodegenerative diseases can be difficult due to overlapping clinical symptoms and the diverse locations of cortical lesions. Still, new neuroimaging and molecular biomarkers have improved clinicians’ diagnostic capabilities in the context of dementia and may lead to the development of more effective treatments. Both genetic and environmental factors may lead to the aggregation of pathological proteins and altered levels of cytokines, such that can trigger the formation of proinflammatory immunological phenotypes. This cascade of pathological changes provides fertile ground for the development of neural plasticity disorders and dementias. Available pharmacotherapy and disease-modifying therapies currently in clinical trials may modulate synaptic plasticity to mitigate the effects neuropathological changes have on cognitive function, memory, and learning. In this article, we review the neural plasticity changes seen in common neurodegenerative diseases from pathophysiological and clinical points of view and highlight potential molecular targets of disease-modifying therapies.

show abstract

“…All major ascending neuromodulatory systems innervate the cerebral cortex, including the PFC and influence the dynamics of persistent activity and cortical WM circuitry (Arnsten et al, 2012). The modulatory actions of acetylcholine (ACh) on cortical function have been of long-standing interest partly because cholinergic dysfunction has been implicated in cognitive and WM deficits that manifest in psychiatric and neurological disorders including Alzheimer's disease (Hampel et al, 2018(Hampel et al, , 2019, dementia associated with Parkinson's disease (Noufi et al, 2019), major depressive disorder (Dagytë et al, 2011), and schizophrenia (Sarter and Bruno, 1998;Dean et al, 2003). Progressive cortical cholinergic deafferentation is a hallmark of Alzheimer's dementia and cholinergic pathology accompanies the cognitive disruption that manifests in the disease (Hampel et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Neuromodulation of Persistent Activity and Working Memory Circuitry in Primate Prefrontal Cortex by Muscarinic Receptors

Vijayraghavan

Everling

2021

Front. Neural Circuits

View full text Add to dashboard Cite

Neuromodulation by acetylcholine plays a vital role in shaping the physiology and functions of cerebral cortex. Cholinergic neuromodulation influences brain-state transitions, controls the gating of cortical sensory stimulus responses, and has been shown to influence the generation and maintenance of persistent activity in prefrontal cortex. Here we review our current understanding of the role of muscarinic cholinergic receptors in primate prefrontal cortex during its engagement in the performance of working memory tasks. We summarize the localization of muscarinic receptors in prefrontal cortex, review the effects of muscarinic neuromodulation on arousal, working memory and cognitive control tasks, and describe the effects of muscarinic M1 receptor stimulation and blockade on the generation and maintenance of persistent activity of prefrontal neurons encoding working memory representations. Recent studies describing the pharmacological effects of M1 receptors on prefrontal persistent activity demonstrate the heterogeneity of muscarinic actions and delineate unexpected modulatory effects discovered in primate prefrontal cortex when compared with studies in rodents. Understanding the underlying mechanisms by which muscarinic receptors regulate prefrontal cognitive control circuitry will inform the search of muscarinic-based therapeutic targets in the treatment of neuropsychiatric disorders.

show abstract

Use of Cholinesterase Inhibitors in Non-Alzheimer’s Dementias

Cited by 36 publications

References 101 publications

Concentration-Dependent Activity of Hydromethylthionine on Clinical Decline and Brain Atrophy in a Randomized Controlled Trial in Behavioral Variant Frontotemporal Dementia

Concentration-Dependent Activity of Hydromethylthionine on Clinical Decline and Brain Atrophy in a Randomized Controlled Trial in Behavioral Variant Frontotemporal Dementia

Molecular Factors Mediating Neural Cell Plasticity Changes in Dementia Brain Diseases

Neuromodulation of Persistent Activity and Working Memory Circuitry in Primate Prefrontal Cortex by Muscarinic Receptors

Contact Info

Product

Resources

About