Impact of age-related cerebral white matter changes on the transition to disability -- the LADIS study: rationale, design and methodology.

Age-related white matter changes (ARWMC) on brain MRI have been associated with cognitive, motor, mood and urinary disturbances. These factors are known to contribute to disability in elderly people, but the impact of ARWMC and of their progression on the transition to disability is not determined. The LADIS (Leukoaraiosis and Disability in the Elderly) study aims at assessing the role of ARWMC as an independent predictor of the transition to disability in initially nondisabled elderly (65-84 years).

Cross-national comparison and validation of the Alzheimer's Disease Assessment Scale: results from the European Harmonization Project for Instruments in Dementia (EURO-HARPID).

Background: The Alzheimer's Disease Assessment Scale (ADAS) is often used in international multicenter trials. Use across countries presupposes correct translation and adaptation of the scale, and maintenance of its psychometric properties.

Objectives: To compare the various translations of the ADAS used in Western Europe, to design internationally harmonized translations and to validate these.

Alzheimer disease ethics--informed consent and related issues in clinical trials: results of a survey among the members of the Research Ethics Committees in Sweden.

The rapid advances in biomedical sciences have induced special moral and ethical attitudes, which ought to be taken into account. One of the most essential issues is the principles for participation in research of subjects with reduced decision-making capacity. We conducted a questionnaire survey among members of the research ethics committees in Sweden to find out their attitudes to a range of ethical issues related to research on subjects with Alzheimer's disease.

Decreased cerebrospinal fluid acetylcholinesterase in patients with subcortical ischemic vascular dementia.

The main objective was to investigate the acetylcholinesterase E (AChE) activity in the cerebrospinal fluid (CSF) of patients with three common dementia disorders. We also wanted to investigate the influence of apolipoprotein E (ApoE) epsilon4 allele possession and CSF-tau level on the CSF-AChE activity in these patients. The study included 17 consecutive patients with subcortical vascular dementia (SVD), 39 with Alzheimer's disease (AD), 14 with frontotemporal dementia (FTD) and 12 controls.

Cross-national comparisons of the Cambridge Cognitive Examination-revised: the CAMCOG-R: results from the European Harmonization Project for Instruments in Dementia.

Background: Transnational and psychometrically appropriate versions of instruments used in the diagnosis of dementia are essential for comparing information between different countries. The Cambridge Examination for Mental Disorders of the Elderly incorporates a brief neuropsychological test battery, Cambridge Cognitive Examination (recently revised version), which provides objective data on performance across a number of cognitive domains.

Objective: To harmonise the Cambridge Cognitive Examination between seven European countries.

Cerebral pattern of pro- and anti-inflammatory cytokines in dementias.

The knowledge regarding putative inflammatory component(s) participating in Alzheimer's disease (AD) and vascular dementia (VAD) is scarce. Recently, we have demonstrated the presence of certain inflammatory cytokines in the cerebrospinal fluid (CSF) of demented patients. Although the initial event(s) triggering the neurodegenerative processes in AD versus VAD may be different and lead to different neuropathological changes, it may initiate a similar cascade of cytokine production in response to neuronal injury.

Subcortical ischaemic vascular dementia.

Vascular dementia is the second most common type of dementia. The subcortical ischaemic form (SIVD) frequently causes cognitive impairment and dementia in elderly people. SIVD results from small-vessel disease, which produces either arteriolar occlusion and lacunes or widespread incomplete infarction of white matter due to critical stenosis of medullary arterioles and hypoperfusion (Binswanger's disease).

Treatment with simvastatin in patients with Alzheimer's disease lowers both alpha- and beta-cleaved amyloid precursor protein.

We investigated the clinical and biological effects of cholesterol-lowering treatment with a statin in 19 patients with Alzheimer's disease. They received simvastatin 20 mg/day for 12 weeks in an open trial. Primary efficacy parameters were the changes after 12 weeks in the cerebrospinal fluid (CSF) levels of beta-amyloid(42) (Abeta(42)), alpha-secretase-cleaved amyloid precursor protein (alpha-sAPP), beta-secretase-cleaved APP (beta-sAPP), tau, phospho-tau and the plasma levels of Abeta(42).

Objective measurement of the alertness level in dementia.

The alertness level of 143 patients with dementia was investigated. The patients were examined clinically and electroencephalographically, and the results were compared with 21 healthy volunteers. Regional brain syndromes were determined clinically.

Biological correlates of clinical subgroups of Alzheimer's disease.

We considered it possible that the differences in clinical symptoms between two suggested subgroups of Alzheimer's disease (AD), AD type I and AD type II, have biological correlates, for instance different metabolic profiles. Therefore, we performed regional cerebral blood flow (rCBF) measurements and investigated the cerebrospinal fluid (CSF) levels of the monoamine metabolites homovanillic acid (HVA), 5-HIAA, and HMPG in 15 patients with AD type I, in 36 patients with AD type II, in a control group and in a contrast group consisting of 16 patients with frontotemporal dementia. The results suggest that there are underlying biological correlates of the phenomenological discrepancies between AD type I and AD type II.

[Clinical investigation of cognitive dysfunction by specialists].

The clinical investigation of the cognitively impaired, or demented, patient includes a clinical bedside examination supported by, for instance, structural and functional brain imaging, analyses of biochemical markers, and genetic analyses. Valuable discussions have been held during the last decade between specialists and primary care physicians to define the clinical elements that should be included in bedside examinations carried out by general practitioners. The present paper is focused instead on the bedside investigation performed by the specialist in the field.

Calcitonin gene-related peptide and calcitonin in the CSF of patients with dementia and depression: possible disease markers.

Cerebrospinal fluid (CSF) was obtained from 32 patients with dementia, 19 healthy controls that were age-matched with the dementia patients, and 29 DSM-IV major depression patients and calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) and calcitonin-like immunoreactivity (CT-LI) measured by RIA. CGRP-LI was lower in the dementia group compared to both the controls and depressed patients (P<.01) after covarying out sex and age.

Decreased CSF-beta-amyloid 42 in Alzheimer's disease and amyotrophic lateral sclerosis may reflect mismetabolism of beta-amyloid induced by disparate mechanisms.

Both tau and beta-amyloid 42 (Abeta42) have been implicated in Alzheimer's disease (AD) and tau alone in frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). These proteins can be measured in the cerebrospinal fluid (CSF); differences from normal CSF levels may reflect pathophysiological mechanisms. Using ELISAs, we investigated the levels of total CSF-tau (here referred to as tau), phosphorylated CSF-tau (phosphotau), and Abeta42 in patients with AD (n = 19), FTD (n = 14), ALS (n = 11) and Parkinson's disease (PD; n = 15) and in age-matched controls (n = 17).

Increased intrathecal levels of the angiogenic factors VEGF and TGF-beta in Alzheimer's disease and vascular dementia.

The aim of the present study was to investigate, in patients with Alzheimer's disease (AD), and vascular dementia (VAD), patterns of local release of vascular endothelial growth factor (VEGF) and transforming growth factor-beta (TGF-beta), two cytokines having a pivotal role in hypoxia-induced angiogenesis. The intrathecal levels of these molecules were related to the clinical severity of these diseases and to the intrathecal levels of beta-amyloid protein. Significantly increased cerebrospinal fluid (CSF) levels of both VEGF and TGF-beta were observed in 20 patients with AD and in 26 patients with VAD compared to healthy controls.