1,721,264 research outputs found
Choline alphoscerate in cognitive decline and in acute cerebrovascular disease: an analysis of published clinical data.
No full textThis paper has reviewed the documentation on the clinical efficacy of choline alphoscerate, a cholinergic precursor, considered as a centrally acting parasympathomimetic drug in dementia disorders and in acute cerebrovascular disease. Thirteen published clinical trials, examining in total 4054 patients, have evaluated the use of choline alphoscerate in various forms of dementia disorders of degenerative, vascular or combined origin, such as senile dementia of the Alzheimer's type (SDAT) or vascular dementia (VaD) and in acute cerebrovascular diseases, such as transitory ischemic attack (TIA) and stroke. Analysis has assessed the design of each study, in particular with respect to experimental design, number of cases, duration of treatment and tests used to evaluate drug clinical efficacy. Most of the ten studies performed in dementia disorders were controlled trials versus a reference drug or placebo. Overall, 1570 patients were assessed in these studies, 854 of which in controlled trials. As detected by validated and appropriate tests, such as Mini Mental State Evaluation (MMSE) in SDAT and Sandoz Clinical Assessment Geriatric (SCAG) in VaD, administration of choline alphoscerate significantly improved patient clinical condition. Clinical results obtained with choline alphoscerate were superior or equivalent to those observed in control groups under active treatment and superior to the results observed in placebo groups. Analysis stresses the clear internal consistency of clinical data gathered by different experimental situations on the drug effect, especially with regard to the cognitive symptoms (memory, attention) characterising the clinical picture of adult-onset dementia disorders. The therapeutic usefulness of choline alphoscerate in relieving cognitive symptoms of chronic cerebral deterioration differentiates this drug from cholinergic precursors used in the past, such as choline and lecithin. Three uncontrolled trials were performed with choline alphoscerate in acute cerebrovascular stroke and TIA, totalling 2484 patients. The results of these trials suggest that this drug might favour functional recovery of patients with cerebral stroke and should be confirmed in future investigations aimed at establish the efficacy of the drug in achieving functional recovery of patients with acute cerebrovascular diseas
The Challenge of Disease-Modifying Therapies in Parkinson's Disease: Role of CSF Biomarkers.
No full textThe development of disease modifying strategies in Parkinson's disease (PD) largely depends on the ability to identify suitable populations after accurate diagnostic work-up. Therefore, patient molecular profiling and disease subtyping are mandatory. Thus far, in clinical trials, PD has been considered to be a "single entity". Conversely, in front of the common feature of nigro-striatal degeneration, PD is pathogenically heterogeneous with a series of several biological and molecular pathways that differently contribute to clinical development and progression. Currently available diagnostic criteria for PD mainly rely on clinical features and imaging biomarkers, thus missing to identify the contribution of pathophysiological pathways, also failing to catch abnormalities occurring in the early stages of disease. Cerebrospinal fluid (CSF) is a promising source of biomarkers, with the high potential for reflecting early changes occurring in PD brain. In this review, we provide an overview on CSF biomarkers in PD, discussing their association with different molecular pathways involved either in pathophysiology or progression in detail. Their potential application in the field of disease modifying treatments is also discussed
Headache and ischemic stroke
No full textHeadache occurs frequently in acute ischemic stroke, but its frequency varies widely among different studies. We have prospectively studied headache features in patients with first-ever ischemic acute stroke and assessed the relationship between headache, stroke location, and etiology. The study included consecutive patients admitted to our Stroke Unit for a first-ever ischemic acute stroke. The study included 154 consecutive patients with ischemic stroke, and 54 of these (35.1%) had headache during stroke onset. Twelve patients (22.2%) with headache during stroke had history of headache; no patients without headache had history of headache. Headache was present in 25.8% (32/124) of the patients with anterior circulation stroke and in 73.3% (22/30) of the patients with posterior circulation stroke (p=0.001). Large artery disease was more frequent with than without headache (40.7% versus 14.0%, p=0.04). Headache was present in more than one-third of the patients with ischemic stroke. All patients with positive history for headache had headache during stroke onset. The cephalic pain was much more common among patients with infarcts in the posterior circulation than in patients in whom the anterior circulation was involved. Headache was more common when the cause of stroke was large artery disease
Prevalence and risk of progression of preclinical Alzheimer's disease stages: A systematic review and meta-analysis
No full textBackground: Alzheimer's disease (AD) pathology begins several years before the clinical onset. The long preclinical phase is composed of three stages according to the 2011National Institute on Aging and Alzheimer's Association (NIA-AA) criteria, followed by mild cognitive impairment (MCI), a featured clinical entity defined as "due to AD", or "prodromal AD", when pathophysiological biomarkers (i.e., cerebrospinal fluid or positron emission tomography with amyloid tracer) are positive. In the clinical setting, there is a clear need to detect the earliest symptoms not yet fulfilling MCI criteria, in order to proceed to biomarker assessment for diagnostic definition, thus offering treatment with disease-modifying drugs to patients as early as possible. According to the available evidence, we thus estimated the prevalence and risk of progression at each preclinical AD stage, with special interest in Stage 3. Methods: Cross-sectional and longitudinal studies published from April 2008 to May 2018 were obtained through MEDLINE-PubMed, screened, and systematically reviewed by four independent reviewers. Data from included studies were meta-analyzed using random-effects models. Heterogeneity was assessed by I 2 statistics. Results: Estimated overall prevalence of preclinical AD was 22% (95% CI = 18-26%). Rate of biomarker positivity overlapped in cognitively normal individuals and people with subjective cognitive decline. The risk of progression increases across preclinical AD stages, with individuals classified as NIA-AA Stage 3 showing the highest risk (73%, 95% CI = 40-92%) compared to those in Stage 2 (38%, 95% CI = 21-59%) and Stage 1 (20%, 95% CI = 10-34%). Conclusion: Available data consistently show that risk of progression increases across the preclinical AD stages, where Stage 3 shows a risk of progression comparable to MCI due to AD. Accordingly, an effort should be made to also operationalize the diagnostic work-up in subjects with subtle cognitive deficits not yet fulfilling MCI criteria. The possibility to define, in the clinical routine, a patient as "pre-MCI due to AD" could offer these subjects the opportunity to use disease-modifying drugs at best
Has the time arrived for cerebrospinal fluid biomarkers in psychiatric disorders?
No full textPsychiatric disorders are currently classified, in the majority of cases, by clinical syndromes. However, advances over the last decade in imaging and biochemical biomarkers in several Central Nervous System (CNS) disorders anticipate the incorporation of some of these markers in the diagnostic work-up of psychiatric conditions. In particular, CSF biomarkers offer the possibility of detecting a wide range of pathophysiological processes in the CNS. Newer CSF markers can measure axonal and synaptic damage, glial activation, and oxidative stress in CNS disorders with high precision. The possibility that these markers can be applied in the differential diagnosis of common psychiatric disorders such as Schizophrenia, Major Depressive or Bipolar Disorders not only to rule out neurodegenerative diseases but also to identify specific biomarker signatures has yet to be explored. In particular, synaptic proteins in CSF could be useful as markers of synaptic and neurotransmitter transmission impairment since these are key molecular features of psychiatric conditions. In this paper we outline the current and potential applications of CSF biomarkers in psychiatric disorders
Cholinergic precursors in the treatment of cognitive impairment of vascular origin: ineffective approaches or need for re-evaluation?
No full textInhibition of endogenous acetylcholine degradation through cholinesterase inhibitors represents a milestone in symptomatic treatment of cognitive symptoms in mild to moderate stages of Alzheimer's disease. Cholinesterase inhibitors are also under investigation for treating cognitive dysfunction of cerebrovascular origin, but to date they do not have specific indication for vascular dementia or vascular cognitive impairment. This paper reviews the main clinical studies assessing the activity of cholinergic precursors in the treatment of adult-onset dementia disorders of vascular origin. The first cholinergic precursor used phosphatidylcholine (lecithin) did not show any clear clinical benefit on symptoms of dementia disorders. The same is not true for other phospholipids involved in choline biosynthetic pathways such as cytidine 5'-diphosphocholine (CDP-choline) and choline alphoscerate for which a modest improvement of cognitive dysfunction in dementia of neurodegenerative and vascular origin is documented. Positive results obtained with selected cholinergic precursors cannot be generalized due to the small numbers of patients studied in appropriate clinical trials. However, they probably would justify reconsideration of the most promising molecules in larger carefully controlled studies
Headache associated with acute ischemic stroke
No full textHeadache associated with strokeHeadache occurs frequently in acute ischemic stroke, but its frequency varies widely among different studies. We have prospectively studied headache features in patients with first-ever ischemic acute stroke and assessed the relationship between headache, stroke location, and etiology. The study included consecutive patients admitted to our Stroke Unit for a first-ever ischemic acute stroke. The study included 154 consecutive patients with ischemic stroke, and 54 of these (35.1%) had headache during stroke onset. Twelve patients (22.2%) with headache during stroke had history of headache; no patients without headache had history of headache. Headache was present in 25.8% (32/124) of the patients with anterior circulation stroke and in 73.3% (22/30) of the patients with posterior circulation stroke (p=0.001). Large artery disease was more frequent with than without headache (40.7% versus 14.0%, p=0.04). Headache was present in more than one-third of the patients with ischemic stroke. Al..
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