Evidence map›Paper›PMID 36115980›Full record

ArticleAlzheimer's research & therapy2022

Cumulative effect of simvastatin, L-arginine, and tetrahydrobiopterin on cerebral blood flow and cognitive function in Alzheimer's disease.

Elizabeth Degrush, Mohammed Salman Shazeeb, David Drachman, Zeynep Vardar, Clifford Lindsay, Matthew J Gounis, Nils Henninger

Registry-linked trialOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Alzheimer's research & therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01439555 (Endothelial Facilitation in Alzheimer's Disease. An Open Label Pilot Study of the Sequential and Cumulative Effects of Simvastatin, L-Arginine, and Sapropterin), which is not on this map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.6field-weighted citation impact, top 18% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT01439555 phase2completednot on this map

Endothelial Facilitation in Alzheimer's Disease. An Open Label Pilot Study of the Sequential and Cumulative Effects of Simvastatin, L-Arginine, and Sapropterin (Kuvan) on Cerebral Blood Flow and Cognitive Function in Patients With Alzheimer's Disease.

TypeinterventionalSponsorUniversity of Massachusetts, WorcesterRan2011 to 2017Enrolled11ConditionsAlzheimer's DiseaseArmsSimvastatin, L-Arginine, Tetrahydrobiopterin
3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 12 citations in OpenAlex.

  1. Trial
  2. Review
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  5. Amino acid metabolism in health and disease.Signal transduction and targeted therapy · 2023
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 1 institution in 1 country.

Elizabeth Degrush *Department of Neurology, University of Massachusetts Chan Medical School, 55 Lake Ave, North, Worcester, MA, 01655, USA. Elizabeth.Degrush@umassmemorial.org.
Mohammed Salman Shazeeb *Image Processing and Analysis Core (iPAC), Department of Radiology, University of Massachusetts Chan Medical School, Worcester, MA, USA.
David DrachmanDepartment of Neurology, University of Massachusetts Chan Medical School, 55 Lake Ave, North, Worcester, MA, 01655, USA.
Zeynep VardarImage Processing and Analysis Core (iPAC), Department of Radiology, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Clifford LindsayImage Processing and Analysis Core (iPAC), Department of Radiology, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Matthew J GounisImage Processing and Analysis Core (iPAC), Department of Radiology, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Nils HenningerDepartment of Neurology, University of Massachusetts Chan Medical School, 55 Lake Ave, North, Worcester, MA, 01655, USA.
University of Massachusetts Chan Medical School · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

objectivesVascular disease is a known risk factor for Alzheimer's disease (AD). Endothelial dysfunction has been linked to reduced cerebral blood flow. Endothelial nitric oxide synthase pathway (eNOS) upregulation is known to support endothelial health. This single-center, proof-of-concept study tested whether the use of three medications known to augment the eNOS pathway activity improves cognition and cerebral blood flow (CBF).

methodsSubjects with mild AD or mild cognitive impairment (MCI) were sequentially treated with the HMG-CoA reductase synthesis inhibitor simvastatin (weeks 0-16), L-arginine (weeks 4-16), and tetrahydrobiopterin (weeks 8-16). The primary outcome of interest was the change in CBF as measured by MRI from baseline to week 16. Secondary outcomes included standard assessments of cognition.

resultsA total of 11 subjects were deemed eligible and enrolled. One subject withdrew from the study after enrollment, leaving 10 subjects for data analysis. There was a significant increase in CBF from baseline to week 8 by ~13% in the limbic and ~15% in the cerebral cortex. Secondary outcomes indicated a modest but significant increase in the MMSE from baseline (24.2±3.2) to week 16 (26.0±2.7). Exploratory analysis indicated that subjects with cognitive improvement (reduction of the ADAS-cog 13) had a significant increase in their respective limbic and cortical CBF.

conclusionsTreatment of mild AD/MCI subjects with medications shown to augment the eNOS pathway was well tolerated and associated with modestly increased cerebral blood flow and cognitive improvement.

trial registrationThis study is registered in https://www. CLINICALTRIALS: gov ; registration identifier: NCT01439555; date of registration submitted to registry: 09/23/2011; date of first subject enrollment: 11/2011.

Indexed as

Alzheimer DiseaseHydroxymethylglutaryl-CoA Reductase InhibitorsArginineBiopterinsCerebrovascular CirculationCognitionHumansNeuropsychological TestsNitric Oxide Synthase Type IIIProof of Concept StudySimvastatinArginineBiopterinsHydroxymethylglutaryl-CoA Reductase InhibitorsNitric Oxide Synthase Type IIIsapropterinSimvastatinAlzheimer’s diseaseArterial spin labelingDementiaEndothelial nitric oxide synthasePerfusion-weighted imagingStatinVascular disease

Identifiers

PMID36115980
PMCPMC9482313
OpenAlexW4296248421

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.