Cholinergic precursors in the treatment of cognitive impairment of vascular origin: Ineffective approaches or need for re-evaluation?

Parnetti, Lucilla; Mignini, Fiorenzo; Tomassoni, Daniele; Traini, Enea; Amenta, Francesco

doi:10.1016/j.jns.2007.01.043

Cited by 110 publications

(101 citation statements)

References 35 publications

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“…In the 1970's, Wecker and Schmidt observed that neurons incorporated more exogenous choline under conditions of reduced cholinergic synthesis and increased neuronal demand [49] , which suggested that the systemic administration of a choline precursor may antagonize biochemical disorders of the cholinergic system. Clinical trials have evaluated the effects of cholinergic precursors -including lecithin (also known as phosphatidylcholine), cytidine 5′-diphosphocholine (CDPcholine or citicoline) and choline alphoscerate -on dementia of vascular origin (reviewed in ref [50] ).…”

Section: Cholinergic Precursorsmentioning

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: Cholinergic Precursorsmentioning

confidence: 99%

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

2009

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“…It is a natural precursor of phospholipid synthesis, or rather serves as a choline source in the metabolic pathways for biosynthesis of acetylcholine and neuronal membrane phospholipids, mainly phosphatidylcholine. [3][4][5][6] Animal studies suggest that CDP choline may protect cell membranes by accelerating resynthesis of phospholipids. CDP choline may also attenuate the progression of ischemic cell damage by suppressing the release of free fatty acids.…”

Section: Introductionmentioning

confidence: 99%

O4‐12‐05: Effectiveness and safety of citicoline in mild vascular cognitive impairment: The IDEALE study

Cotroneo¹,

Putignano²,

Fantò³

et al. 2012

Alzheimer's & Dementia

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Background:The studio di intervento nel decadimento vascolare lieve (IDEALE study) was an open multicenter Italian study, the aim of which was to assess the effectiveness and safety of oral citicoline in elderly people with mild vascular cognitive impairment. Methods:The study was performed in 349 patients. The active or citicoline group was composed of 265 patients and included 122 men and 143 women of mean age 79.9 ± 7.8 years selected from six Italian regions. Inclusion criteria were age $ 65 years, Mini-Mental State Examination (MMSE) score $ 21, subjective memory complaints but no evidence of deficits on MMSE, and evidence of vascular lesions on neuroradiology. Those with probable Alzheimer's disease were excluded. The control group consisted of 84 patients, including 36 men and 48 women of mean age 78.9 ± 7.01 (range 67-90) years. Patients included in the study underwent brain computed tomography or magnetic resonance imaging, and plasma dosage of vitamin B12, folate, and thyroid hormones. Functional dependence was investigated by scores on the Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL) scales, mood was assessed by the Geriatric Depression Scale (GDS), and behavioral disorders using the Neuropsychiatric Inventory scale. Comorbidity was assessed using the Cumulative Illness Rating Scale. An assessment was made at baseline (T0), after 3 months (T1), and after 9 months (T2, ie, 6 months after T1). The main outcomes were an improvement in MMSE, ADL, and IADL scores in the study group compared with the control group. Side effects were also investigated. The study group was administered oral citicoline 500 mg twice a day throughout the study. Results: MMSE scores remained unchanged over time (22.4 ± 4 at T0; 22.7 ± 4 at T1; 22.9 ± 4 at T2), whereas a significant difference was found between the study and control groups, both in T1 and in T2. No differences were found in ADL and IADL scores between the two groups. A slight but not statistically significant difference was found in GDS score between the study and control groups (P = 0.06). No adverse events were recorded. Conclusion: In this study, citicoline was effective and well tolerated in patients with mild vascular cognitive impairment. Citicoline activates biosynthesis of phospholipids in neuronal membranes, increases brain metabolism as well as norepinephrine and dopamine levels in the central nervous system, and has neuroprotective effects during hypoxia and ischemia. Therefore, citicoline may be recommended for patients with mild vascular cognitive impairment.

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“…Th e deacylated, water-soluble PC analogue GPC rapidly delivers choline to the brain across the BBB (Parnetti et al 2007), and it may be present in the irradiated area where the cytokine-mediated actions are expected. Indeed, the i.v.…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective effects of phosphatidylcholine and L-alpha-glycerylphosphorylcholine in experimental inflammation

Tőkés¹

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Cholinergic precursors in the treatment of cognitive impairment of vascular origin: Ineffective approaches or need for re-evaluation?

Cited by 110 publications

References 35 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

O4‐12‐05: Effectiveness and safety of citicoline in mild vascular cognitive impairment: The IDEALE study

Neuroprotective effects of phosphatidylcholine and L-alpha-glycerylphosphorylcholine in experimental inflammation

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