Dark-field and directional dark-field on low-coherence x ray sources with random mask modulations: validation with SAXS anisotropy measurements.

Phase-contrast imaging, dark-field, and directional dark-field imaging are recent x ray imaging modalities that have been demonstrated to reveal different information and contrast from those provided by conventional x ray imaging. Access to these new types of images is currently limited because the acquisitions require coherent sources such as synchrotron radiation or complicated optical setups. This Letter demonstrates the possibility of efficiently performing phase-contrast, dark-field, and directional dark-field imaging on a low-coherence laboratory system equipped with a conventional x ray tube, using a simple, fast, and robust single-mask technique.

A protective personal factor against disability and dependence in the elderly: an ordinal regression analysis with nine geographically-defined samples from Spain.

BACKGROUND: Sense of Coherence (SOC) is defined as a tendency to perceive life experiences as comprehensible, manageable and meaningful. The construct is split in three major domains: Comprehensibility, Manageability, and Meaningfulness. SOC has been associated with successful coping strategies in the face of illness and traumatic events and is a predictor of self-reported and objective health in a variety of contexts. In the present study we aim to evaluate the association of SOC with disability and dependence in Spanish elders. METHODS: A total of 377 participants aged 75 years or over from nine locations across Spain participated in the study (Mean age: 80.9 years; 65.3% women). SOC levels were considered independent variables in two ordinal logistic models on disability and dependence, respectively. Disability was established with the World health Organization-Disability Assessment Schedule 2.0 (36-item version), while dependence was measured with the Extended Katz Index on personal and instrumental activities of daily living. The models included personal (sex, age, social contacts, availability of an intimate confidant), environmental (municipality size, access to social resources) and health-related covariates (morbidity). RESULTS: High Meaningfulness was a strong protective factor against both disability (Odds Ratio [OR] = 0.50; 95% Confidence Interval [CI] = 0.29-0.87) and dependence (OR = 0.33; 95% CI = 0.19-0.58) while moderate and high Comprehensibility was protective for disability (OR = 0.40; 95% CI = 0.22-0.70 and OR = 0.39; 95%CI = 0.21-0.74), but not for dependence. Easy access to social and health resources was also highly protective against both disability and dependence. CONCLUSIONS: Our results are consistent with the view that high levels of SOC are protective against disability and dependence in the elderly. Elderly individuals with limited access to social and health resources and with low SOC may be a group at risk for dependence and disability in Spain.

The contributions of filaments and cross-bridges to sarcomere compliance in skeletal muscle.

Force generation in the muscle sarcomere is driven by the head domain of the myosin molecule extending from the thick filament to form cross-bridges with the actin-containing thin filament. Following attachment, a structural working stroke in the head pulls the thin filament towards the centre of the sarcomere, producing, under unloaded conditions, a filament sliding of ∼ 11 nm. The mechanism of force generation by the myosin head depends on the relationship between cross-bridge force and movement, which is determined by compliances of the cross-bridge (C(cb)) and filaments. By measuring the force dependence of the spacing of the high-order myosin- and actin-based X-ray reflections from sartorius muscles of Rana esculenta we find a combined filament compliance (Cf) of 13.1 ± 1.2 nm MPa(-1), close to recent estimates from single fibre mechanics (12.8 ± 0.5 nm MPa(-1)). C(cb) calculated using these estimates is 0.37 ± 0.12 nm pN(-1), a value fully accounted for by the compliance of the myosin head domain, 0.38 ± 0.06 nm pN(-1), obtained from the intensity changes of the 14.5 nm myosin-based X-ray reflection in response to 3 kHz oscillations imposed on single muscle fibres in rigor. Thus, a significant contribution to C(cb) from the myosin tail that joins the head to the thick filament is excluded. The low C(cb) value indicates that the myosin head generates isometric force by a small sub-step of the 11 nm stroke that drives filament sliding at low load. The implications of these results for the mechanism of force generation by myosins have general relevance for cardiac and non-muscle myosins as well as for skeletal muscle.

X-ray scattering of nematic liquid crystal nanodispersion with negative dielectric anisotropy [Invited].

A nematic liquid crystal (LC) mixture was doped with harvested ferroelectric BaTiO3 nanoparticles and investigated with wide- and small-angle x-ray scattering upon heating from the nematic to the isotropic phase. At moderate temperatures, colloidal crystallites were observed. LC test cells with homeotropic anchoring were placed in the x-ray beam and the realignment of the LC director was investigated upon applying an electric field.

[Comparison between aquatic-biodanza and stretching for improving quality of life and pain in patients with fibromyalgia]. / Comparación entre biodanza en medio acuático y stretching en la mejora de la calidad de vida y dolor en los pacientes con fibromialgia.

OBJECTIVE: To determine the level of improvement, as regards pain, impact on fibromyalgia and depression, achieved by patients with fibromyalgia by comparing aquatic biodanza and stretching exercises. DESIGN: Randomised controlled trial with two intervention groups. LOCATION: Five health centres (Almeria). PATIENTS: A total of 82 fibromyalgia patients between 18 and 65 years old, diagnosed by American College of Rheumatology criteria, were included, with 12 patients declining to take part in the study. The 70 remaining patients were randomly assigned to two groups of 35 patients each: aquatic biodanza and stretching exercises. Those who did not attend in at least 14 sessions or changed their treatment during the studio were excluded. The final sample consisted of 19 patients in aquatic biodanza group and 20 in stretching group. The limitations of the study included, the open evaluation design and a sample size reduced by defaults. MAIN MEASURES: The outcome measures were sociodemographic data, quality of life (Fibromyalgia Impact Questionnaire), pain (McGill-Melzack questionnaire; and Visual Analogue Scale), pressure algometry (Wagner FPI10 algometer) and depression (Beck Inventory). These were carried out before and after a 12-week therapy. RESULTS: The mean age of the sample was 55.41 years. The mean period from diagnosis was 13.44 years. The sample consisted mainly of housewives. There were significant differences (P<.05) between groups, in pain (P<.01), fibromyalgia impact (P<.01), and depression (P<.04) after the treatment. CONCLUSIONS: The biodanza aquatic exercises improve pain and quality of life in fibromyalgia patients.

Prevalence of dementia and major dementia subtypes in Spanish populations: a reanalysis of dementia prevalence surveys, 1990-2008.

BACKGROUND: This study describes the prevalence of dementia and major dementia subtypes in Spanish elderly. METHODS: We identified screening surveys, both published and unpublished, in Spanish populations, which fulfilled specific quality criteria and targeted prevalence of dementia in populations aged 70 years and above. Surveys covering 13 geographically different populations were selected (prevalence period: 1990-2008). Authors of original surveys provided methodological details of their studies through a systematic questionnaire and also raw age-specific data. Prevalence data were compared using direct adjustment and logistic regression. RESULTS: The reanalyzed study population (aged 70 year and above) was composed of Central and North-Eastern Spanish sub-populations obtained from 9 surveys and totaled 12,232 persons and 1,194 cases of dementia (707 of Alzheimer's disease, 238 of vascular dementia). Results showed high variation in age- and sex-specific prevalence across studies. The reanalyzed prevalence of dementia was significantly higher in women; increased with age, particularly for Alzheimer's disease; and displayed a significant geographical variation among men. Prevalence was lowest in surveys reporting participation below 85%, studies referred to urban-mixed populations and populations diagnosed by psychiatrists. CONCLUSION: Prevalence of dementia and Alzheimer's disease in Central and North-Eastern Spain is higher in females, increases with age, and displays considerable geographic variation that may be method-related. People suffering from dementia and Alzheimer's disease in Spain may approach 600,000 and 400,000 respectively. However, existing studies may not be completely appropriate to infer prevalence of dementia and its subtypes in Spain until surveys in Southern Spain are conducted.

Prevalence of neuropsychiatric symptoms in Alzheimer's disease and vascular dementia.

OBJECTIVE: The study aimed to describe the prevalence and severity of neuropsychiatric symptoms in patients with Alzheimer's disease (AD) and vascular dementia (VaD). PATIENTS AND METHODS: We prospectively studied 65 patients with dementia, 37 met the criteria of NINCDS-ADRDA for probable AD and 28 the clinical and radiological criteria of NINDS-AIREN for VaD. Among VaD patients, 22 met the radiological criteria for subcortical VaD. The Minimental State Examination (MMSE) and the Neuropsychiatric Inventory (NPI) were used to evaluate cognitive and neuropsychiatric symptoms. All patients underwent a neuroimaging study (CT scan and/or MRI). Patients were not treated with antidementia or psychotropic drugs. RESULTS: Age, gender, educational level and MMSE scores did not differ between patients (p >0.05). The total prevalence of neuropsychiatric symptoms was similar in both groups (AD 94.6% vs. VaD 96.4%, p= 0.727). Sleep disturbances (35.1% v 3.6%, p =0.002) and appetite changes (37.8% v 14.3%, p = 0.032) were more prevalent in AD patients than in VaD patients who met the NINDS-AIREN criteria. Sleep disturbances (35.1% v 4.5%, p =0.008), appetite changes (37.8% v 13.6%, p = 0.047) and aberrant motor behaviour (24.3% v 0%, p =0.012) were more prevalent in AD patients than in subcortical VaD. The total scores for sleep disturbance, appetite changes and aberrant motor behavioural were higher in AD patients (p < 0.05). CONCLUSIONS: There were no significant differences between AD and VaD patients, except that sleep disturbances, appetite changes and aberrant motor behaviour that were more prevalent and severe in AD.

Prevalence of neuropsychiatric symptoms in elderly patients with dementia in Mungialde County (Basque Country, Spain).

BACKGROUND: Determination of the prevalence of neuropsychiatric symptoms in elderly patients with dementia in Mungialde. METHODS: 108 subjects with dementia, who participated in a door-to-door epidemiological study, were included. The 12-item Spanish version of the Neuropsychiatric Inventory was used to evaluate these symptoms. RESULTS: The prevalence of at least 1 neuropsychiatric symptom was found to be 76.90% for all dementia types, 73.50% in patients with Alzheimer's disease (AD), 80% for the Parkinson-Lewy body dementia complex (PLBD), 78.60% for vascular dementia (VD) and 100% for frontotemporal dementia (FTD). Apathy was found to be the most prevalent symptom for all dementia types and in patients with AD (53.70 and 54.30%, respectively). The next most prevalent symptoms were anxiety, depression and sleep disturbances (35.20, 32.40 and 30.60%) for all dementia types, and anxiety and depression (32.10 and 30.90%) in patients with AD. The most prevalent symptoms in patients with PLBD were apathy, appetite changes, sleep disturbances and agitation (50% each); in patients with VD they were apathy, depression and anxiety (42.90% each), and in patients with FTD they were apathy, anxiety and aberrant motor activity (100% each). CONCLUSIONS: Neuropsychiatric symptoms were found to be prevalent in patients with dementia, irrespective of dementia type.

Risk factors for dementia in the epidemiological study of Munguialde County (Basque Country-Spain).

BACKGROUND: Prevalence of degenerative dementias and dementias associated with cerebrovascular disease is increasing. Dementia is one of the most significant public health problem. In recent years, the role of vascular risk factors (hypertension, diabetes mellitus and hypercholesterolemia) and depression has been evaluated.The incidence of dementia and risk factors has not been fully investigated in Spain. The aim of this study was to identify the risk factors for dementia, Alzheimer's disease (AD) and vascular dementia (VD) in elderly people in Munguialde County (Spain). METHODS: A two phase, door-to-door populational study was performed. Demographic variables and the presence of vascular risk factors and depression were recorded. The MMSE, the DSM-IV and the conventional criteria for AD and VD were used in the evaluation. The odds ratio for each risk factor was calculated by logistic regression analysis. RESULTS: 1756 healthy subjects and 175 patients with dementia participated in the study. Of these, 133 had AD, 15 VD and the remainder other dementias. The risk factors for dementia and AD were female sex (OR = 1.67 and 1.97, respectively); age (OR = 1.14 and 1.15); stroke (OR = 7.84 and 3); and depression (OR = 53.08 and 3.19). Stroke was the only risk factor for VD (OR = 119). CONCLUSION: Greater age, female sex, stroke and depression increase the risk of suffering dementia, AD and VD. The relationship between depression, vascular risk factors and dementia has clear public health implications. Prevention and early treatment of vascular risk factors and depression may have an important impact in lowering the risk of dementia and could modify the natural history of the disease.

One-Year Reference Norms of Cognitive Change in Spanish Old Adults: Data from the NEURONORMA Sample.

OBJECTIVE: Serial cognitive assessments are useful for many purposes, such as monitoring cognitive decline or evaluating the result of an intervention. In order to determine if an observed change is reliable and meaningful, longitudinal reference data from non-clinical samples are needed. Since neuropsychological outcomes are affected by language and cultural background, cognitive tests should be adapted, and country-based norms collected. The lack of cross-sectional normative data for Spanish population has been partially remediated, but there is still a need of reliable change norms. This paper aims to give an initial response to this need by providing several reliable change indices (RCI) for 1-year follow-up in a Spanish sample. METHOD: A longitudinal observational study was designed. A total of 122 healthy subjects over age 50 were evaluated twice (M = 369.5, SD= 10.7 days) with the NEURONORMA battery. Scores changes were analyzed, and simple discrepancy scores, standard deviation indices, RCI, and standardized regression-based scores were calculated. RESULTS: Significant improvements were observed in variables related to memory, both verbal and visual, visuospatial function, and the completion time of complex problems. Reference tables for several RCI are provided for their use in clinical settings. CONCLUSIONS: Our results confirm the existence of heterogeneous practice effects after 1 year, and support the recommendation of using reliable change norms to avoid misdiagnosis in repeated assessments. This study provides with initial, preliminary norms of cognitive change for its use in Spanish elders. Further studies on larger samples and different inter-visit intervals are still needed.

Association of the C47T Polymorphism in SOD2 with Amnestic Mild Cognitive Impairment and Alzheimer's Disease in Carriers of the APOEε4 Allele.

Oxidative stress plays an important part in amnestic mild cognitive impairment (aMCI), the prodromal phase of Alzheimer's disease (AD). Recent evidence shows that polymorphisms in the SOD2 gene affect the elimination of the reactive oxygen species (ROS) generated in mitochondria. The aim of this study was to determine whether the functional rs4880 SNP in the SOD2 gene is a risk factor associated with aMCI and sporadic AD. 216 subjects with aMCI, 355 with AD, and 245 controls have been studied. The SNP rs4880 of the SOD2 gene was genotyped by RT-PCR and the APOE genotype was determined by PCR and RFLPs. Different multinomial logistic regression models were used to determine the risk levels for aMCI and AD. Although the T allele of the SOD2 rs4880 SNP gene (rs4880-T) is not an independent risk for aMCI or AD, this allele increases the risk to aMCI patients carrying at least one APOEε4 allele. Moreover, rs4880-T allele and APOEε4 allele combination has been found to produce an increased risk for AD compared to aMCI reference patients. These results suggest that APOEε4 and rs4880-T genotype may be a risk for aMCI and a predictor of progression from aMCI to AD.

Cognitive and behavioral symptoms in Parkinson's disease patients with the G2019S and R1441G mutations of the LRRK2 gene.

OBJECTIVE: To compare the cognitive and psychiatric status of patients with Parkinson's disease related to the G2019S and the R1441G mutations of the LRRK2 gene (LRRK2-PD) and idiopathic Parkinson's disease (iPD) patients. METHODS: We examined cognition and psychiatric symptoms in 27 patients with LRRK2-PD (12 G2019S and 15 R1441G) and 27 iPD patients. RESULTS: The groups were similar in age, education, disease duration, levodopa equivalent daily dose, and Unified Parkinson's Disease Rating Scale (UPDRS) II-IV; however, the LRRK2-PD showed less impairment on UPDRS-I (2.0 ± 1.7 vs. 4.2 ± 2.8, p = 0.003). The LRRK2-PD presented less frequent subjective cognitive complaints (18.5% vs. 63.0%, p = 0.002), and mild cognitive impairment or dementia (25.9% vs. 59.2%, p = 0.027). They also showed less impairment on scales for general cognition (Mattis dementia rating scale 131.2 ± 10.9 vs. 119 ± 24.0, p = 0.022), episodic verbal memory (Rey's auditory verbal learning test, immediate recall 39.2 ± 9.5 vs. 27.6 ± 12.8 p < 0.001, delayed recall 7.2 ± 3.7 vs. 4.7 ± 4.0 p = 0.022), and the Neuropsychiatric Inventory (9.7 ± 9.2 vs. 20.5 ± 14.3, p = 0.004, significant differences for apathy and hallucinations). The LRRK2-PD subjects were less frequently treated with antipsychotic medication (0% vs. 25.9%, p = 0.010). There were no significant differences between G2019S and R1441G mutation carriers. CONCLUSIONS: Mutations of the LRRK2 gene might cause PD associated with less cognitive and neuropsychiatric impairment as compared to iPD.

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.

Cognitive and neuroimaging profiles in mild cognitive impairment and Alzheimer's disease: data from the Spanish Multicenter Normative Studies (NEURONORMA Project).

The aim of this study was to characterize the neuropsychological and neuroimaging profiles of mild cognitive impairment (MCI) and Alzheimer's disease (AD) patients, and to study the magnitude of the differences by comparing both outcomes with healthy subjects in a cross-sectional manner. Five hundred and thirty-five subjects (356 cognitively normal adults (CONT), 79 MCI, and 100 AD) were assessed with the NEURONORMA neuropsychological battery. Thirty CONT, 23 MCI, and 23 AD subjects from this sample were included in the neuroimaging substudy. Patients' raw cognitive scores were converted to age and education-adjusted scaled ones (range 2-18) using co-normed reference values. Medians were plotted to examine the cognitive profile. MRIs were processed by means of FreeSurfer. Effect size indices (Cohen's d) were calculated in order to compare the standardized differences between patients and healthy subjects. Graphically, the observed cognitive profiles for MCI and AD groups produced near to parallel lines. Verbal and visual memories were the most impaired domains in both groups, followed by executive functions and linguistic/semantic ones. The largest effect size between AD and cognitively normal subjects was found for the FCSRT (d = 4.05, AD versus CONT), which doubled the value obtained by the best MRI measure, the right hippocampus (d = 1.65, AD versus CONT). Our results support the notion of a continuum in cognitive profile between MCI and AD. Neuropsychological outcomes, in particular the FCSRT, are better than neuroimaging ones at detecting differences among subjects.

Neuropsychiatric symptoms in amnestic mild cognitive impairment: increased risk and faster progression to dementia.

INTRODUCTION: Neuropsychiatric symptoms (NPS) are common in mild cognitive impairment (MCI) but its role as a predictive factor for the progression to dementia is still not clear. The objective of this study is to identify NPS that predict the progression from amnestic MCI (a-MCI) to dementia using an easy to administer screening tool for NPS. MATERIAL AND METHODS: 132 patients with a-MCI were assessed for NPS by the Neuropsychiatric Inventory (NPI) and followed to detect progression to dementia. RESULTS: The mean follow-up time was 3.5±2.9 years and rate of progression to dementia 28.8%. Two items of NPI were found to be independent risk factors for progression, nighttime behavioural disturbance (hazard ratio(HR)=2.2, 95%CI=1.10-4.43), anxiety (HR=2.5, 95%CI=1.01-6.20) and apathy (HR=2.2, 95%CI=1.003-4.820). The risk of progression increased with higher score on NPI (HR=1.046 per point, 95%CI=1.019- 1.073), and with a higher number of items of NPI affected (HR=3.6 per item, 95%CI=2.0-6.4). Faster progression to dementia was observed in patients with either nighttime behavioural disturbance, apathy or anxiety (4.6 vs. 8.3 years, 5.3 vs. 8.4 years and 3.0 vs. 7.7 years respectively, p < 0.01) as well as in those with a higher number of items affected (no items = 9.2 years, 1-3 items = 6.6 years and > 3 items = 2.9 years, p < 0.001). CONCLUSIONS: Assessing a broad spectrum of NPS can help identify patients with a-MCI presenting a higher risk for progression to dementia. This can be useful to select patients for closer follow-up, clinical trials and future therapeutic interventions.

Doping a mixture of two smectogenic liquid crystals with barium titanate nanoparticles.

A mixture of two smectic liquid crystals was doped with harvested ferroelectric barium titanate nanoparticles and investigated with wide- and small-angle X-ray scattering during cooling from the isotropic phase. A decrease in the isotropic to nematic and in the nematic to partially bilayer smectic-A(d) (SmA(d)) phase transition temperatures was observed accompanied by an increase of the layer spacing in the SmA(d) phase.

[Effectiveness of aquatic biodance on sleep quality, anxiety and other symptoms in patients with fibromyalgia]. / Efectividad de la biodanza acuática sobre la calidad del sueño, la ansiedad y otros síntomas en pacientes con fibromialgia.

BACKGROUND AND OBJECTIVE: To analyze the effects of an aquatic biodance based therapy on sleep quality, anxiety, depression, pain and quality of life in fibromyalgia patients. PATIENTS AND METHOD: Randomized controlled trial with 2 groups. Fifty-nine patients were assigned to 2 groups: experimental group (aquatic biodance) and control group (stretching). The outcome measures were quality of sleep (Pittsburgh questionnaire), anxiety (State Anxiety Inventory), depression (Center for Epidemiologic Studies Depression Scale), pain (visual analogue scale, pressure algometry and McGill) and quality of life (Fibromyalgia Impact Questionnaire) before and after a 12-week therapy. RESULTS: After treatment, we observed significant differences in the experimental group (P<.05) on sleep quality (49.7%), anxiety (14.1%), impact of fibromyalgia (18.3%), pain (27.9%), McGill (23.7%) and tender points (34.4%). CONCLUSIONS: Aquatic biodance contributed to improvements in sleep quality, anxiety, pain and other fibromyalgia symptoms.

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.

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.