Biomedical subjects

A Wallin

Publications and source records attributed to A Wallin.

184 records · Page 11Linked to original sources

PubMedDate not supplied

Subtypes of vascular dementia.

The challenge of describing subgroups is particularly important in vascular dementia, which, in contrast to more stereotypic processes affecting cognitive function, is better thought of as several syndromes rather than as a disease. Many current diagnostic descriptions lack a strong empiric basis. Some of the categories now in use suffer from a priori assumptions about causality and pattern associations, which themselves have not been validated. The so-called mixed dementia syndrome may have been underrepresented in our estimation of dementia subtypes, in comparison with so-called pure vascular causes. Within the vascular syndrome, whether seen in isolation or in combination with other causes of dementia, the relative contributions of white matter changes as compared with multiple cortical strokes needs to be clarified. It remains a matter of controversy as to whether prolonged or chronic intermittent cerebral ischemia is a statistically important part of the dementia. The variable relation between clinical presentation and neuroimaging localization has important consequences for understanding the pathophysiology of cognitive impairment arising from vascular causes. Recent data also suggest that we should focus away from both the Alzheimer disease model of dementia and the multi-infarct model of vascular dementia. There are important opportunities available to clinicians from many disciplines to collaborate in precise clinical descriptions of large numbers of patients to advance our understanding of the spectrum of vascular cognitive impairment.

Brain Diseases↗

PubMedDate not supplied

Is subcortical vascular dementia a clinical entity for clinical drug trials?

Several therapeutic trials have been performed for vascular dementia, with drugs differing in type and mechanism of action. The results have been almost invariably inconclusive. Given the current notion that there are different subtypes of vascular dementia according to pathophysiological mechanisms, it is reasonable to suspect that one of the main causes of the disappointing results was that the study samples included patients not fitting with the rationale of selective treatments. Testing this hypothesis is difficult because characterization of patients in relation to different subtypes of vascular dementia is not available for most studies. However, attempts are ongoing to reclassify patients entered in some trials for post hoc subgroup analyses with some preliminary interesting results. We propose that (1) specific subtypes of vascular dementia should be the target in any single trial using a treatment with a proper rationale; and (2) subcortical vascular dementia, caused by small vessel disease leading to lacunar infarcts and subcortical white matter changes, represents a clinically and radiologically well-defined entity to be considered for future trials designed specifically for testing adequate drugs.

Cerebral Cortex↗

PubMedDate not supplied

Cerebrospinal fluid markers of pathogenetic processes in vascular dementia, with special reference to the subcortical subtype.

There is a need for improvement of the diagnosis of vascular dementia (VaD). Today, the clinician has to rely on clinical examination, history, and, possibly, brain imaging to identify cerebrovascular damage and other signs of VaD. The clinical diagnosis of subcortical VaD may be difficult because the clinical manifestation of this disorder is often similar to that of Alzheimer disease. There are also mixed forms of the two disorders. Biochemical diagnostic markers, which reflect the pathogenetic processes in the brain, would add to the accuracy of the diagnosis. There are some interesting candidate markers: the cerebrospinal fluid (CSF)/serum albumin ratio could be used to identify blood-brain barrier damage to the small intracerebral vessels, CSF sulfatide to identify ongoing demyelination of the white matter, CSF neuron-specific enolase to identify ongoing neuronal degeneration, and CSF tau protein and CSF neurofilament light protein to identify ongoing axonal degeneration. None of these potential markers is specific to subcortical VaD, but together and used in conjunction with the conventional diagnostic workup, they may be of diagnostic value.

Alzheimer Disease↗

PubMedDate not supplied

Nimodipine in subcortical vascular dementia trial.

Vascular dementia (VaD) is a heterogeneous pathology currently regarded as the result of a variety of causes. Different types of VaD can be identified according to different criteria. This heterogeneity might be one of the causes of the controversial results observed, up to now, in clinical trials. Recently, the 10th revision of the International Classification of Diseases (ICD-10) explicitly identified subcortical VaD as a well-defined subgroup. Abnormalities of white matter are clearly detectable with computed tomography or magnetic resonance scans. The clinicoradiological association of dementia, blood hypertension, and other vascular risk factors, extensive white matter lesions, and small subcortical infarcts might be considered as a clinical univocal entity. Following the encouraging results of a preliminary pilot study, the above-mentioned criteria were followed to define a population of patients to be enrolled in a double-blind, parallel-groups, placebo-controlled clinical trial with nimodipine, which has been proposed as a drug that can improve cognitive functions in patients with VaD. The paper discusses the protocol design of this ongoing trial and its main entry criteria, with particular emphasis on the definition of the population to be enrolled. Implication for future trials in subcortical VaD are discussed further.

Aged↗