Donepezil in vascular dementia

Wilkinson, David; Doody, Rachelle S.; Helme, Robert D.; Taubman, Kevin; Mintzer, J.; Kertesz, Andrew; Pratt, Raymond D.

doi:10.1212/01.wnl.0000078943.50032.fc

Cited by 360 publications

(215 citation statements)

References 30 publications

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“…Six-month treatment with donepezil was shown to significantly improve Clinical Dementia Rating (CDR) scores and activities of daily living in VaD patients (excluding AD and mixed dementia (VaD/AD) patients) [93] . In a later study, donepezil was further demonstrated to significantly improve cognitive function, global function, and activities of daily living versus placebo-treated subjects in a randomized, double-blind, placebo-controlled, 24-week clinical trial comprising 1219 patients with mild to moderate cognitive decline due to probable or possible VaD (according to the NINCDS/AIREN criteria and the Hachinski Ischemia Scale), although adverse effects were reported in the higher-dose group [71,92,94,95] . Moreover, a recent randomized double-blind trial of donepezil in CADASIL showed a significant benefit on executive function and processing speed [46] , although this result was later questioned by Schneider [45] .…”

Section: Donepezilmentioning

confidence: 99%

Cholinergic deficiency involved in vascular dementia: possible mechanism and strategy of treatment

2009

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Vascular dementia (VaD) is a progressive neurodegenerative disease with a high prevalence. Several studies have recently reported that VaD patients present cholinergic deficits in the brain and cerebrospinal fluid (CSF) that may be closely related to the pathophysiology of cognitive impairment. Moreover, cholinergic therapies have shown promising effects on cognitive improvement in VaD patients. The precise mechanisms of these cholinergic agents are currently not fully understood; however, accumulating evidence indicates that these drugs may act through the cholinergic anti-inflammatory pathway, in which the efferent vagus nerve signals suppress pro-inflammatory cytokine release and inhibit inflammation, although regulation of oxidative stress and energy metabolism, alleviation of apoptosis may also be involved. In this paper, we provide a brief overview of the cholinergic treatment strategy for VaD and its relevant mechanisms of anti-inflammation.

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Section: Donepezilmentioning

confidence: 99%

Cholinergic deficiency involved in vascular dementia: possible mechanism and strategy of treatment

2009

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“…There is evidence that treatments approved for cognitive symptoms in patients with Alzheimer's disease may also show symptomatic benefit in patients with vascular cognitive impairment. Although not specifically shown in patients with CAA, trials in patients with vascular dementia indicate that donepezil and galantamine have a modest effect on global cognition reflected by an improvement of 1 to 2 points on the cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog) (donepezil [131][132][133][134] and galantamine 135,136 ) and improvement on a test for executive functioning. 135 The benefits of memantine and rivastigmine in vascular cognitive impairment are less well established.…”

Section: Treatmentmentioning

confidence: 99%

Ischemic brain injury in cerebral amyloid angiopathy

Reijmer

Veluw

Greenberg

2015

J Cereb Blood Flow Metab

123

102

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Cerebral amyloid angiopathy (CAA) is a common form of cerebral small vessel disease and an important risk factor for intracerebral hemorrhage and cognitive impairment. While the majority of research has focused on the hemorrhagic manifestation of CAA, its ischemic manifestations appear to have substantial clinical relevance as well. Findings from imaging and pathologic studies indicate that ischemic lesions are common in CAA, including white-matter hyperintensities, microinfarcts, and microstructural tissue abnormalities as detected with diffusion tensor imaging. Furthermore, imaging markers of ischemic disease show a robust association with cognition, independent of age, hemorrhagic lesions, and traditional vascular risk factors. Widespread ischemic tissue injury may affect cognition by disrupting white-matter connectivity, thereby hampering communication between brain regions. Challenges are to identify imaging markers that are able to capture widespread microvascular lesion burden in vivo and to further unravel the etiology of ischemic tissue injury by linking structural magnetic resonance imaging (MRI) abnormalities to their underlying pathophysiology and histopathology. A better understanding of the underlying mechanisms of ischemic brain injury in CAA will be a key step toward new interventions to improve long-term cognitive outcomes for patients with CAA.

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“…According to the authors, there are insufficient data to support widespread use of these drugs in vascular dementia. The trials meeting the selection criteria for this metaanalysis included three donepezil (307, 308, 319) [31][32][33], two galantamine (GAL-INT-6 and 26) [34,35], one rivastigmine (VantagE) [36], and two memantine trials (MMM300 and 500) [37,38], comprising 3,093 patients on the study drugs and 2,090 patients on placebo (table 1). Cognitive effects on the Alzheimer's Disease Assessment Scale were significant for all drugs, ranging from a mean difference of -1.10 (95% CI -2.15 to -0.05) for rivastigmine to -2.17 for 10 mg daily donepezil (95% CI -2.98 to -1.35).…”

Section: Curative Treatmentmentioning

confidence: 99%

Is It Possible to Treat Vascular Dementia?

Zekry¹

2009

Dementia in Clinical Practice

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Randomized controlled trials of primary and secondary prevention of vascular dementia demonstrate real effects on the cause or progression of disease (disease-modifying treatment). These strategies lead to a reduction in all cerebrovascular risk factors, in particular hypertension. Such treatment may prevent dementia by reducing stroke and possibly by other mechanisms that remain undetermined, such as those involved in neurodegeneration and cell death. Curative treatment of vascular dementia, particularly given recent studies on cholinesterase inhibitors (rivastigmine, donepezil and galantamine) and memantine, is still ineffective. There is insufficient evidence to support widespread use of these drugs in vascular dementia. Particular considerations should be taken into account in clinical trials. Vascular dementia is a heterogeneous disease with different subtypes and mechanisms. Therefore, well-designed, adequately powered trials accounting for this heterogeneity, with better clinical definitions and an assessment and detection of cognitive and global changes specific to vascular dementia, are needed.

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Donepezil in vascular dementia

Abstract: Donepezil-treated patients demonstrated significant improvements in cognition and global function compared with placebo-treated patients, and donepezil was well tolerated.

Cited by 360 publications

References 30 publications

Cholinergic deficiency involved in vascular dementia: possible mechanism and strategy of treatment

Cholinergic deficiency involved in vascular dementia: possible mechanism and strategy of treatment

Ischemic brain injury in cerebral amyloid angiopathy

Is It Possible to Treat Vascular Dementia?

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