Neuroprotection in Vascular Dementia

Abstract

Vascular dementia (VaD) is the second most common form of dementia after Alzheimer’s disease (AD), and one of the major causes of mental and physical disability in developed countries. As such, the identification and implementation of strategies which prevent the development of the condition or enable improvements in patients with VaD are healthcare objectives of the first order. VaD is now regarded as a combined group of clinical-pathological entities rather than one disease, that is, multiple pathogenic mechanisms and lesion types underlie a cognitive impairment of vascular origin. The clinical diagnosis of VaD is complex and difficult because of the heterogeneous nature of its clinical presentation and progression and the low sensitivity of existing clinical criteria. Moreover, there is growing evidence of the epidemiological significance of mixed forms of dementia, and that ischemic processes may precipitate and exacerbate cognitive impairment in AD. Numerous compounds have been proposed as potentially useful in the treatment of patients with VaD, comprising vasodilatative, antithrombotic, hemorrheological, nootropic, antiserotoninergic and, most recently, antiglutamatergic and cholinergic approaches. In spite of some initially favorable reports based on the use of memantine, donepezil and galantamine, there is as yet no conclusive evidence of a definitive treatment for VaD. Unsatisfactory results from VaD drug trials may be attributed in part to the diversity of the patients included (underlying pathogenic mechanisms, number, type, and location of vascular lesions), and to methodological limitations in the design of the trials (outcome measures, end-points, size, follow-up period). The treatment of modifiable vascular risk factors – hypertension, diabetes mellitus, hypercholesterolemia and heart disease – is an important strategy for the reduction of the risk of dementia, and is likely to slow the progress of cognitive decline.

Management of oxidative stress and other pathologies in Alzheimer’s disease

“…While neurotoxic forms of Aβ were found to stimulate Cu-mediated oxidation of ascorbate anion (AscH − ) to ascorbyl radical anion (Asc •− ) (Eq. 9), the nontoxic form of Aβ did not (Ryglewicz et al 2002).…”

Cerebrolysin in Vascular Dementia: Improvement of Clinical Outcome in a Randomized, Double-Blind, Placebo-Controlled Multicenter Trial

“…Over the years, substantial attention has focused on potential treatments for VaD, including calcium-channel blockers, acetylsalicylic acid, platelet aggregation inhibitors, citicoline, the g-aminobutyic acid derivates piracetam and oxiracetam, the serotonin 5-HT2 receptor antagonist naftidrofuryl, the xanthine derivates pentoxifylline and propentofylline, and chlorinesterase inhibitors. 5 The efficacy of purely symptomatic treatment of VaD remains a matter of a debate. According to a recently published meta-analysis on the efficacy and adverse effects of cholinesterase inhibitors (eg, donepezil, rivastigmine, galantamine) and the N-methyl d-aspartate receptor antagonist memantine, these symptomatic medications provide only small benefits in cognition of uncertain clinical significance in patients with mild to moderate VaD.…”

Serum Amyloid Beta Peptides in Patients with Dementia and Age-Matched Non-Demented Controls as Detected by Surface-Enhanced Laser Desorption Ionisation-Time of Flight Mass Spectrometry (SELDI-TOF MS)

“…Alzheimer's Disease (AD) is the most common form of dementia [2] and Vascular Dementia (VaD) is the second in the developed world [3].…”