Assessment of low-flow CSF drainage as a treatment for AD

Silverberg, Gerald D.; Levinthal, Elliott C.; Sullivan, E. V.; Blöch, D.; Chang, Steven D.; Leverenz, James B.; Flitman, Stephen; Winn, Robert K.; Marciano, Frederick F.; Saul, Thomas; Huhn, Stephen L.; Mayo, Martha; McGuire, Dawn

doi:10.1212/01.wnl.0000031794.42077.a1

Cited by 88 publications

(51 citation statements)

References 31 publications

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“…The majority of trials (n = 94) used at least one cognitive outcome, 25,27-29, 51,52,55,57,64,66,68,75,78,[86][87][88][89][90][91][92][93]97,104,106,107,110,112,115,118,119,121,123,125,126,130,131,133,134,[137][138][139][140]143,145,146 with a variety of 16 measures used. ADLs were measured in 55 trials, using 12 measures.…”

Section: Published Trialsmentioning

confidence: 99%

Development of a core outcome set for disease modification trials in mild to moderate dementia: a systematic review, patient and public consultation and consensus recommendations

Webster

Groskreutz

Grinbergs-Saull

et al. 2017

Health Technol Assess

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Background: There is currently no disease-modifying treatment available to halt or delay the progression of the disease pathology in dementia. An agreed core set of the best-available and most appropriate outcomes for disease modification would facilitate the design of trials and ensure consistency across disease modification trials, as well as making results comparable and meta-analysable in future trials. Objectives: To agree a set of core outcomes for disease modification trials for mild to moderate dementia with the UK dementia research community and patient and public involvement (PPI). Data sources: We included disease modification trials with quantitative outcomes of efficacy from (1) references from related systematic reviews in workstream 1; (2) searches of the Cochrane Dementia and Cognitive Improvement Group study register, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, EMBASE, Latin American and Caribbean Health Sciences Literature and PsycINFO on 11 December 2015, and clinical trial registries [International Standard Randomised Controlled Trial Number (ISRCTN) and clinicaltrials.gov] on 22 and 29 January 2016; and (3) hand-searches of reference lists of relevant systematic reviews from database searches. Review methods: The project consisted of four workstreams. (1) We obtained related core outcome sets and work from co-applicants. (2) We systematically reviewed published and ongoing disease modification trials to identify the outcomes used in different domains. We extracted outcomes used in each trial, recording how many used each outcome and with how many participants. We divided outcomes into the domains measured and searched for validation data. (3) We consulted with PPI participants about recommended outcomes. (4) We presented all the synthesised information at a conference attended by the wider body of National Institute for Health Research (NIHR) dementia researchers to reach consensus on a core set of outcomes. Results: We included 149 papers from the 22,918 papers screened, referring to 125 individual trials. Eighty-one outcomes were used across trials, including 72 scales [31 cognitive, 12 activities of daily living (ADLs), 10 global, 16 neuropsychiatric and three quality of life] and nine biological techniques. We consulted with 18 people for PPI. The conference decided that only cognition and biological markers are core measures of disease modification. Cognition should be measured by the Mini Mental State Examination (MMSE) or the Alzheimer’s Disease Assessment Scale – Cognitive subscale (ADAS-Cog), and brain changes through structural magnetic resonance imaging (MRI) in a subset of participants. All other domains are important but not core. We recommend using the Neuropsychiatric Inventory for neuropsychiatric symptoms: the Disability Assessment for Dementia for ADLs, the Dementia Quality of Life Measure for quality of life and the Clinical Dementia Rating scale to measure dementia globally. Limitations: Most of the trials inclu...

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Section: Published Trialsmentioning

confidence: 99%

Development of a core outcome set for disease modification trials in mild to moderate dementia: a systematic review, patient and public consultation and consensus recommendations

Webster

Groskreutz

Grinbergs-Saull

et al. 2017

Health Technol Assess

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“…These trials can be divided into the following 5 categories of surgical approaches: cerebrospinal fluid (CSF) shunting [4,5,6,7], intraventricular infusions [8,9,10,11,12,13,14,15,16], tissue grafting [17,18,19], gene therapy [20,21], and electrical neural stimulation [22,23,24,25,26] (table 1). The specific treatment strategies within each category are described in detail below (table 2).…”

Section: Methodsmentioning

confidence: 99%

The Neurosurgical Treatment of Alzheimer's Disease: A Review

Laxton

Stone

Lozano

2014

Stereotact Funct Neurosurg

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Background: Alzheimer's disease (AD) is a debilitating neurological illness of increasing prevalence. Because many patients are affected and current treatments have limited effectiveness, other therapeutic strategies are urgently needed. Objectives: Here we provide a review of the neurosurgical approaches that have been attempted or are currently being investigated for the treatment of AD. Methods: Computerized database searches identified all of the published studies in the English-language literature examining the surgical treatment of AD since 1950. Results: The following 5 categories of neurosurgical treatment were identified: cerebrospinal fluid shunting, intraventricular infusions, tissue grafting, gene therapy, and electrical neural stimulation. Conclusions: While none of the neurosurgical approaches applied to the treatment of AD have proven effective to date, recent trials involving gene therapy and electrical neural stimulation are showing promising early results. Larger trials investigating these treatments have been proposed or are currently under way.

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“…63 Small-scale studies have shown symptomatic improvement in patients with AD in response to nimodipine 64,65 and ventriculoperitoneal shunting. 66 The use of nimodipine was based on the theory that AD interferes directly with cerebral calcium metabolism; and the use of shunting was based on the hypothesis that it would improve the clearance of waste materials from CSF. However, these observations could also be explained by failure of Monro-Kellie homeostasis in patients with dementia and any such failure could contribute to the onset and severity of cognitive impairment.…”

Section: Microvascular Angiopathymentioning

confidence: 99%

Changing Concepts of Cerebrospinal Fluid Hydrodynamics: Role of Phase-Contrast Magnetic Resonance Imaging and Implications for Cerebral Microvascular Disease

Stivaros

Jackson

2007

Neurotherapeutics

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Summary: Phase-contrast magnetic resonance imaging (PC-MRI) or flow-sensitive MRI can be used to noninvasively measure intracranial vascular and CSF flow. Monro-Kellie homeostasis is the complex compensatory mechanism for the increase in intracranial blood volume during systole. Through PC-MRI techniques, our understanding of Monro-Kellie homeostasis and the associated intracranial hydrodynamics has greatly improved. Failure of this homeostatic mechanism has been implicated in a wide range of cerebral disorders, including vascular and Alzheimer's dementia, late-onset depression, benign and secondary intracranial hypertension, communicating and normal pressure hydrocephalus, and age-related white matter changes. The most common mode of homeostatic failure is due to vascular disease with decreased cerebral arterial compliance. This has wide-reaching implications in the investigation of patients with cerebral vascular disease. Here we discuss the role of PC-MRI in the study of cerebral hydrodynamics and the current understanding of Monro-Kellie homeostasis in both healthy and disease states. Quantitative assessment of the changes in this homeostatic mechanism using PC-MRI has important implications in the development of biomarkers of vascular involvement in disease with application in diagnosis, treatment planning, phenotype identification, and outcome assessment in clinical trials.

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Assessment of low-flow CSF drainage as a treatment for AD

Cited by 88 publications

References 31 publications

Development of a core outcome set for disease modification trials in mild to moderate dementia: a systematic review, patient and public consultation and consensus recommendations

Development of a core outcome set for disease modification trials in mild to moderate dementia: a systematic review, patient and public consultation and consensus recommendations

The Neurosurgical Treatment of Alzheimer's Disease: A Review

Changing Concepts of Cerebrospinal Fluid Hydrodynamics: Role of Phase-Contrast Magnetic Resonance Imaging and Implications for Cerebral Microvascular Disease

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