[Approach to dysphagia in advanced dementia]. / Abordaje de la disfagia en la demencia avanzada.

From the onset, dementia affects the patient's nutritional status, producing anorexia, weight loss, feeding apraxia and dysphagia. Distinct strategies are required in each of the stages of this disease, starting with awareness and knowledge of the problem and its prompt detection. In dementia, dysphagia usually appears in advanced phases, when the patient is often institutionalized. When dysphagia is suspected, the patient's tolerance must be evaluated by the volume/viscosity test, environmental and postural strategies should be introduced, and the texture of the diet should be modified. This is a complex task requiring the involvement of a properly trained interdisciplinary team, able to provide information and alternatives and integrate the family environment in the patient's care. The adapted diet should be based on the traditional diet that can also be combined with artificial supplements to provide a varied diet that increases patients', caregivers' and relatives' satisfaction. Tube feeding has shown no nutritional benefits in patients with advanced dementia. Therefore, we propose assisted oral feeding as the most natural and appropriate form of feeding in these patients, always respecting their previously expressed wishes.

Lrrk2-associated parkinsonism is a major cause of disease in Northern Spain.

Herein we describe a comparative clinical and genetic study of Lrrk2-associated parkinsonism in Northern Spain. In our sample from the Basque region, Lrrk2 R1441G and G2019S account for 15 out of 50 kindreds (30%) with familial Parkinson's disease. We observe common founder haplotypes for both R1441G and G2019S carriers. Our findings highlight the importance of Lrrk2 parkinsonism in this population and may have important consequences for its extended Diaspora in North, Central and South Americas.

Serum albumin and health in older people: Review and meta analysis.

Albumin is the most abundant plasmatic protein. It is only produced by the liver and the full extent of its metabolic functions is not known in detail. One of the main roles assigned to albumin is as an indicator of malnutrition. There are many factors, in addition to nutrition, that influence levels of albumin in plasma. The main aim of this review is to assess the clinical significance of albumin in elderly people in the community, in hospital and in care homes. Following the review, it can be stated that age is not a cause of hypoalbuminemia. Albumin is a good marker of nutritional status in clinically stable people. Significant loss of muscle mass has been observed in elderly people with low albumin levels. Hypoalbuminemia is a mortality prognostic factor in elderly people, whether they live in the community or they are in hospital or institutionalized. Low levels of albumin are associated to worse recovery following acute pathologies. Inflammatory state and, particularly, high concentrations of IL-6 and TNF-alpha, are two of the main influencing factors of hypoalbuminemia. In elderly patients with a hip fracture, albumin levels below 38 g/L are associated to a higher risk of post-surgery complications, especially infections. Further research is needed on the impact of nutritional intervention upon albumin levels and on the outcomes in elderly people in the community, in hospital and in care.

5-Hydroxytryptamine 6 receptor (5-HT(6)) receptor and apolipoprotein E (ApoE) polymorphisms in patients with Alzheimer's disease in the Basque Country.

Although there is considerable evidence implicating apolipoprotein E (ApoE) epsilon4 in the development of the Alzheimer's disease (AD), additional factors are also known to be involved. Thus, an association has been described between C267T polymorphism of the 5-hydroxytryptamine 6 receptor (5-HT(6)) receptor gene and AD. This case-control study analyzes the ApoE and 5-HT(6) receptor polymorphisms in 173 cases and 102 age and sex matched controls from Araba and Bizkaia (The Basque Country, Spain). The analysis of ApoE showed the frequencies of epsilon4 allele to be significantly higher in AD patients (0.292) than in the controls (0.083). When 5-HT(6) receptor polymorphism was analyzed, a greater frequency of 267C allele was observed in AD patients than in controls, though the difference was not statistically significant. Likewise regarding ApoE epsilon4 status, no statistically significant difference was observed. In conclusion, the association of ApoE epsilon4 to AD in a sample of patients from the Basque Country is confirmed, though the association to C267T polymorphism of the 5-HT(6) receptor has not been observed.

Oestrogen receptor polymorphisms are an associated risk factor for mild cognitive impairment and Alzheimer disease in women APOE {varepsilon}4 carriers: a case-control study.

OBJECTIVES: Examine the role of single nucleotide polymorphisms (SNPs) in the oestrogen receptor (ER) genes: rs9340799, rs2234693, rs2228480 (in the ESR1 gene) and rs4986938 (in the ESR2 gene) as a risk factor for amnesic mild cognitive impairment (MCIa) and Alzheimer's disease (AD) and its possible association with the apolipoprotein E (APOE) gene. DESIGN: We have investigated the independent and combined association of different alleles of the oestrogen receptor genes and APOE*ε4 allele with cognitive impairment using a case-control design. SETTING: Participants were prospectively recruited from the neurology departments of several Basque Country hospitals. PARTICIPANTS: This study comprised 816 Caucasian participants who were aged 50 years and older: 204 MCIa, 350 sporadic patients with AD and 262 healthy controls. PRIMARY AND SECONDARY OUTCOME MEASURES: Clinical criteria and neuropsychological tests were used to establish the diagnostic groups (MCIa, AD and healthy controls). A dichotomous variable was used for each allele and genotype and the association with MCIa and AD was established using Logistic Regression Models. RESULTS: Neither alleles nor genotypes of SNPs rs9340799, rs2234693, rs2228480 and rs4986938 of oestrogen receptor genes (ESR1 and ESR2) are independently associated with the risk of MCIa or AD. However, the genetic profile created with the combination of the less represented alleles of these SNPs (expressed as XPAA) was associated with an increased risk for MCIa (OR=3.30, 95% CI 1.28 to 8.54, p=0.014) and AD (OR=5.16, 95% CI 2.19 to 12.14, p<0.001) in women APOE*ε4 allele carriers. CONCLUSIONS: The less represented alleles of SNPs studied are associated with MCIa and AD in APOE*E4 carriers. In particular, the genetic profile created with the less represented alleles of ESR1 and ESR2 SNPs are associated with an increased risk for MCIa and AD in women APOEε4 allele carriers.

[Role of genetics in the etiology of synucleinopathies]. / Papel de la genética en la etiología de las sinucleinopatías.

The protein family known as synucleins is composed of α-, ß- and γ-synuclein. The most widely studied is the α-synuclein protein due to its participation in essential processes of the central nervous system. Neurotoxicity of this protein is related to the presence of multiplications (duplications and triplications) and point mutations in the gene sequence of the α-synuclein gene (SNCA), differential expression of its isoforms and variations in post-transductional modifications. Neurotoxicity is also related to cytoplasmic inclusions known as Lewy bodies (LBs) and Lewy neurites (LNs), which are also present in α-synucleinopathies. In general, the ß-synuclein protein, codified by the SNCB gene, acts as a regulator of processes triggered by α-synuclein and its function is altered by variations in the gene sequence, while γ-synuclein, codified by the SNCG gene, seems to play a major role in certain tumoral processes.

[Genetic profiles of longevity and healthy cognitive aging in nonagenarians from the Basque Country]. / Perfiles genéticos de longevidad y envejecimiento saludable en nonagenarios del País Vasco.

INTRODUCTION: Currently there are notable differences in the aging of individuals in modern populations. While some of them enjoy a long healthy aging, others develop neurodegenerative diseases, such as Alzheimer's disease (AD). Environmental factors are critical, but genetics could explain the differences observed. It has recently been postulated that longevity genes might also be neuroprotective. OBJECTIVES: To assess whether certain genetic variants associated with longevity might have a neuroprotective effect. METHODS: The subjects of this study are people older than 90 years. We will collect sociodemographic and clinical data and multiple assessments, cognitive, functional, anthropometric, nutritional, sensory and physical each participant. In addition, 64 SNPs loci distributed in 13 candidate genes FOXO3, SIRT1, TOMM40, APOE, PICALM, COMT, CETP, CLU, CR1, IL-6, PCK-1, ZNF224 and ACE will be analysed by Taqman array. RESULTS: It is hoped to gain more knowledge about under/over-represented alleles in nonagenarians. Furthermore, comparison of the genetic characteristics of nonagenarians with AD with those free of disease will enable links to be seen between certain alleles with protection or the risk of AD. Associated information on the participants will create subgroups showing the interactions between environment and genetic variation in relation to healthy aging and AD. CONCLUSION: The study of the genetic variability of nonagenarians can give us information on the alleles associated with longevity and neuroprotection.

Polymorphism in the cholesterol 24S-hydroxylase gene (CYP46A1) associated with the APOEpsilon3 allele increases the risk of Alzheimer's disease and of mild cognitive impairment progressing to Alzheimer's disease.

BACKGROUND: Late-onset Alzheimer's disease (LOAD) is associated with changes in certain proteins, such as ApoE and Cyp46A1, of the elimination route for cerebral cholesterol. The main lipoprotein involved in its transport is ApoE whose Epsilon4 allele is the least efficient. However, the presence or absence of this allele does not determine the development of LOAD, which implies the existence of other susceptibility factors associated with the disease, such as the CYP46A1 gene that encodes the enzyme cholesterol 24S-hydroxylase. OBJECTIVE: To find new data to contribute to the evaluation of whether the presence of the T allele in the polymorphic site rs754203 of the CYP46A1 gene leads to a greater risk of developing mild cognitive impairment (MCI) and LOAD. Furthermore, given the link between APOE and CYP46A1, we proceeded to relate both genotypes in each of the patient groups studied. METHODS: We studied MCI and LOAD patients and also carried out an analysis of those MCI patients who progressed from a mild cognitive deterioration to a clinically evident Alzheimer's disease during the study. RESULTS: The frequency of the CYP46A1-T allele in the LOAD patients with APOEpsilon3 alleles is significantly higher with respect to the control group; the same occurs in the group made up of LOAD patients together with the MCI patients who progressed to LOAD. The risk of developing LOAD when this allelic combination exists is 2.262 times higher (95% CI 1.337-4.202). However, having the CYP46A1-T allele does not increase the risk of suffering from LOAD in carriers of the APOEpsilon4 allele, probably because the transport of cholesterol is already affected in such patients and possibly masks the effect of the CYP46A1-T allele. CONCLUSIONS: The CYP46A1-T allele increases the risk of suffering from LOAD in persons carrying the APOEpsilon3 allele.