Masitinib for mild-to-moderate Alzheimer's disease: results from a randomized, placebo-controlled, phase 3, clinical trial.

Background: Masitinib is an orally administered tyrosine kinase inhibitor that targets activated cells of the neuroimmune system (mast cells and microglia). Study AB09004 evaluated masitinib as an adjunct to cholinesterase inhibitor and/or memantine in patients with mild-to-moderate dementia due to probable Alzheimer's disease (AD).

Methods: Study AB09004 was a randomized, double-blind, two parallel-group (four-arm), placebo-controlled trial.

The health status: the ignored risk factor in dementia incidence. NEDICES cohort.

Background: The causes of the dementia decrease in affluent countries are not well known but health amelioration could probably play a major role. Nevertheless, although many vascular and systemic disorders in adult life are well-known risk factors (RF) for dementia and Alzheimer disease (AD), health status is rarely considered as a single RF.

Aim: To analyse whether the health status and the self-perceived health (SPH) could be RF for dementia and AD and to discuss its biological basis.

Is milk and dairy intake a preventive factor for elderly cognition (dementia and Alzheimer's)? A quality review of cohort surveys.

Milk and dairy (M&D) is a longstanding human food with widespread use. Many studies showed the preventive capacity of M&D in several human health disorders, but its utility in others is under discussion. Aging has been associated to elderly cognitive decline including dementia-Alzheimer syndrome (Dem-AD).

[Impact of hospital admission on centenarians admitted due to an acute illness. A description of a series of 165 cases and comparison with the literature].

Introduction: The number of centenarians is increasing with the aging of the Spanish population. This age group might present different clinical features from younger groups. This study was carried out to determine the impact hospital admission on centenarians with an acute disease.

Evaluation of Candidate Genes Related to Neuronal Apoptosis in Late-Onset Alzheimer’s Disease.

The objective of this study was to identify genetic variation in genes encoding death receptors and signals that modulate their activity. After conducting a meta-analysis with five previous genome-wide association studies and aggregated data, the most significant signals, (TNF locus: rs2395488, rs2534672, and rs9267445; and FASLG locus: rs730278), were replicated in 1,046 cases and 372 controls. The rs2395488 and rs2534672 markers showed a modest protective effect (OR = 0.

Assessing the role of the TREM2 p.R47H variant as a risk factor for Alzheimer's disease and frontotemporal dementia.

A non-synonymous genetic rare variant, rs75932628-T (p.R47H), in the TREM2 gene has recently been reported to be a strong genetic risk factor for Alzheimer's disease (AD). Also, rare recessive mutations have been associated with frontotemporal dementia (FTD).

Genetic study of neurexin and neuroligin genes in Alzheimer's disease.

The interaction between neurexins and neuroligins promotes the formation of functional synaptic structures. Recently, it has been reported that neurexins and neuroligins are proteolytically processed by presenilins at synapses. Based on this interaction and the role of presenilins in familial Alzheimer's disease (AD), we hypothesized that dysfunction of the neuroligin-neurexin pathway might be associated with AD.

[Myelodysplastic syndrome in the elderly: comprehensive geriatric assessment and therapeutic recommendations].

The onset of myelodysplastic syndromes (MDS) is usually around the age of 70. Despite this, most clinical trials are restricted to younger subjects. Thus, the management of elderly patients with MDS is not always optimal.

Genetic association of complement receptor 1 polymorphism rs3818361 in Alzheimer's disease.

Complement receptor 1 gene polymorphism rs3818361 was recently shown to increase the risk of Alzheimer's disease (AD). We performed an independent replication study of this genetic variant in 2,470 individuals from Spain. By applying an allelic model, we observed a trend toward an association between this marker and late-onset AD susceptibility in our case-control study (odds ratio = 1.

[Efficiency of acute geriatric units: a meta-analysis of controlled studies].

Objective: After analysing the effectiveness in the reduction in the incidence of functional impairment and a higher probability of returning home between elderly patients hospitalised due to an acute medical illness cared for in acute geriatric units (AGU) compared to conventional care units, we propose to assess the efficiency of this care.

Material And Methods: A systematic review and meta-analysis was made of controlled studies (randomised, no randomised and case-control) that compared care in UGA with care in conventional hospital units of patients of 65 years and over with an acute medical illness. Studies on administrative data bases, those that evaluated care of a single disease, and those that assessed units with care in the acute and sub-acute phase were excluded.

The membrane-spanning 4-domains, subfamily A (MS4A) gene cluster contains a common variant associated with Alzheimer's disease.

Background: In order to identify novel loci associated with Alzheimer's disease (AD), we conducted a genome-wide association study (GWAS) in the Spanish population.

Methods: We genotyped 1,128 individuals using the Affymetrix Nsp I 250K chip. A sample of 327 sporadic AD patients and 801 controls with unknown cognitive status from the Spanish general population were included in our initial study.

The MTHFD1L gene rs11754661 marker is not associated with Alzheimer's disease in a sample of the Spanish population.

The MTHFD1L gene SNP variant rs11754661 was found to increase the risk of Alzheimer's disease in a recent Whole Genome Association Study. We have carried out an independent study of this genetic variant in 2467 individuals from Spain. We found no evidence of association between the MTHFD1L marker and susceptibility to Alzheimer's disease in our sample.

The CALHM1 P86L polymorphism is a genetic modifier of age at onset in Alzheimer's disease: a meta-analysis study.

The only established genetic determinant of non-Mendelian forms of Alzheimer's disease (AD) is the ε4 allele of the apolipoprotein E gene (APOE). Recently, it has been reported that the P86L polymorphism of the calcium homeostasis modulator 1 gene (CALHM1) is associated with the risk of developing AD. In order to independently assess this association, we performed a meta-analysis of 7,873 AD cases and 13,274 controls of Caucasian origin (from a total of 24 centers in Belgium, Finland, France, Italy, Spain, Sweden, the UK, and the USA).

Estrogen receptor alpha gene variants are associated with Alzheimer's disease.

The present research is aimed at assessing the role of 3 estrogen receptor alpha (ESR1) gene variants in late onset Alzheimer's disease (AD) susceptibility. One thousand one hundred thirteen unrelated late onset sporadic AD patients, 1109 healthy controls and 121 neurologically healthy elderly controls were used to carry out case-control genetic association studies with ESR1 rs3844508, rs2234693, and ESR1 noncoding deletion 1 (ESR1-NCD1) polymorphisms. Thirty-five healthy male samples were used for molecular analyses.

Genome-wide analysis of genetic loci associated with Alzheimer disease.

Context: Genome-wide association studies (GWAS) have recently identified CLU, PICALM, and CR1 as novel genes for late-onset Alzheimer disease (AD).

Objectives: To identify and strengthen additional loci associated with AD and confirm these in an independent sample and to examine the contribution of recently identified genes to AD risk prediction in a 3-stage analysis of new and previously published GWAS on more than 35,000 persons (8371 AD cases).

Design, Setting, And Participants: In stage 1, we identified strong genetic associations (P < 10(-3)) in a sample of 3006 AD cases and 14,642 controls by combining new data from the population-based Cohorts for Heart and Aging Research in Genomic Epidemiology consortium (1367 AD cases [973 incident]) with previously reported results from the Translational Genomics Research Institute and the Mayo AD GWAS.

CALHM1 P86L polymorphism is associated with late-onset Alzheimer's disease in a recessive model.

CALHM1 gene coding non-synonymous SNP P86L (rs2986017) was reported to increase the risk of Alzheimer's disease (AD) in a recent study. We have investigated this genetic variant in 2470 individuals from Spain to conduct an independent replication study of the proposed SNP marker. By applying a recessive model, we observed weak evidence of an association between P86L mutation and late-onset AD (LOAD) susceptibility in our case-control study (OR =1.

GOLPH2 gene markers are not associated with Alzheimer's disease in a sample of the Spanish population.

GOLPH2 gene SNP variants Rs10868366 and Rs7019241 were reported to decrease the risk of Alzheimer's disease in a recent Whole Genome Association Study. We have investigated these genetic variants in 2470 individuals from Spain to conduct an independent replication study of the proposed SNP markers. We found no evidence of association between GOLPH2 markers and susceptibility to Alzheimer's disease in our series.

Effectiveness of acute geriatric units on functional decline, living at home, and case fatality among older patients admitted to hospital for acute medical disorders: meta-analysis.

Objective: To assess the effectiveness of acute geriatric units compared with conventional care units in adults aged 65 or more admitted to hospital for acute medical disorders.

Design: Systematic review and meta-analysis.

Data Sources: Medline, Embase, and the Cochrane Library up to 31 August 2008, and references from published literature.

Instrumental activities of daily living in the screening of dementia in population studies: a systematic review and meta-analysis.

Background: Despite the fact that the current definitions of dementia in the DSM-IV and ICD-10 require functional deterioration for the diagnosis of dementia, it is not necessary a formal evaluation of functional capacity.

Objectives: To examine the efficiency of functional assessment as a method of screening dementia in population studies.

Methods: This systematic review was based on information from MEDLINE, EMBASE, Index Médico Español (IME), and related articles.

Factors associated with the positive impact of caring for elderly and dependent relatives.

Until recent years, the research on caregivers of dependent dwelling elder subjects has dealt with the negative aspects of caregiving (e.g. depression, anxiety, anger).