Dataset Information

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

ABSTRACT:

Background and objectives

Vascular 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).

Methods

Subjects 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.

Results

A 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.

Conclusions

Treatment 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 registration

This 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.

SUBMITTER: Degrush E

PROVIDER: S-EPMC9482313 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Degrush Elizabeth E Shazeeb Mohammed Salman MS Drachman David D Vardar Zeynep Z Lindsay Clifford C Gounis Matthew J MJ Henninger Nils N

Alzheimer's research & therapy 20220917 1

<h4>Background and objectives</h4>Vascular 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).<h4>Methods</h4>Subjects with mild AD or mi ...[more]

PMID: 36115980

Similar Datasets

Project description:BackgroundThe immediate and longer-term effects of hemodialysis on cerebral circulation, cerebral structure, and cognitive function are poorly understood.MethodsIn a prospective observational cohort study of 97 adults (median age 59 years) receiving chronic hemodialysis, we used transcranial Doppler ultrasound to measure cerebral arterial mean flow velocity (MFV) throughout dialysis. Using a well validated neuropsychological protocol, we assessed cognitive function during and off dialysis and after 12 months of treatment. We also used brain magnetic resonance imaging (MRI) to assess atrophy, white matter hyperintensities (WMHs), and diffusion parameters, and tested correlations between MFV, cognitive scores, and changes on MRI.ResultsMFV declined significantly during dialysis, correlating with ultrafiltrate volumes. Percentage of decline in MFV correlated with intradialytic decline in cognitive function, including global function, executive function, and verbal fluency. At follow-up, 73 patients were available for repeat testing, 34 of whom underwent repeat MRI. In a subgroup of patients followed for 12 months of continued dialysis, percentage of decline in MFV correlated significantly with lower global and executive function and with progression of WMH burden (a marker of small vessel disease). Twelve of 15 patients who received renal transplants during follow-up had both early and follow-up off-dialysis assessments. After transplant, patients' memory (on a delayed recall test) improved significantly; increased fractional anisotropy of white matter (a measure of cerebral diffusion) in these patients correlated with improving executive function.ConclusionsPatients undergoing hemodialysis experience transient decline in cerebral blood flow, correlating with intradialytic cognitive dysfunction. Progressive cerebrovascular disease occurred in those continuing dialysis, but not in transplanted patients. Cognitive function and cerebral diffusion improved after transplant.

Dataset Information

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

Background and objectives

Methods

Results

Conclusions

Trial registration

Clinicaltrials

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets