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Biomedical subjects

R Blesa

Publications and source records attributed to R Blesa.

At least 37 records · Page 2Linked to original sources
PubMed1999

A presenilin 1 mutation (Ser169Pro) associated with early-onset AD and myoclonic seizures.

OBJECTIVE: To characterize the mutation responsible for early-onset AD in a large Spanish kindred. BACKGROUND: Mutations in the presenilin 1 (PS1) gene have been identified and are known to be responsible for 18 to 50% of familial early-onset AD cases. METHODS: Patients were characterized clinically. The proband was further studied with EEG, CSF analysis, CT, brain biopsy, and histology. Other members were studied using EEG, CT, MRI, and SPECT. Genetic analysis of PS1 was performed using PCR amplification of PS1 exons and direct sequencing followed by PS1 modeling of the normal and mutant PS1 proteins. RESULTS: A novel mutation (Ser169Pro) in exon 6 of the PS1 gene was identified in different affected members. The Ser169Pro mutation is located at a site of the PS1 protein that is not a cluster of mutations. The mutation was not present in 100 general population controls and in 50 unrelated sporadic AD cases. The Ser169Pro mutation is associated with generalized myoclonic seizures several years after the initial symptoms of AD, a very early AD onset (< or =35 years), and a rapidly progressive cognitive decline. CONCLUSIONS: The absence of the PS1 Ser169Pro mutation in the general population and in sporadic AD cases together with its detection in the affected members of this kindred suggests that it is a pathogenic mutation. The serine to proline change predicts a kink in the alpha-helix of the transmembrane domain of the PS1 protein that could radically disrupt its normal structure. Further characterization of the effect of this mutation could help identify the function of the PS1 protein and the pathogenic mechanisms of AD.

Alzheimer Disease↗
PubMed1998

Alpha-antichymotrypsin gene polymorphism and risk for Alzheimer's disease in the Spanish population.

The alpha-antichymotrypsin (ACT) and the ApoE polymorphisms have been determined in 136 Alzheimer's disease (AD) patients and in 92 age-matched controls. Only a borderline significant difference is found when comparing the overall ACT/AA genotype frequency between AD patients and controls (chi2, P = 0.08). However this difference is attributable entirely and significantly to the ApoE epsilon4 non-carrier AD group (chi2, P = 0.004). No differences are found in the ACT/AA genotype frequency of the ApoE epsilon4 AD carrier group as compared controls (chi2, P = 0.98) in contrast with previous works. These findings support that the presence of the ACT/AA genotype is a genetic risk factor for developing AD in non-ApoE epsilon4 carriers subjects in our population.

Aged↗
PubMed1998

Clinical validity and utility of the interview for deterioration of daily living in dementia for Spanish-speaking communities NORMACODEM Group.

The assessment of activities of daily living is a central procedure in the diagnosis of dementia. Few instruments in the field allow for early detection of functional decline because the items they use refer mainly to basic activities of daily living (BADL), which do not become compromised until later in the disease process. The Interview for Deterioration of Daily Living in Dementia (IDDD) may be a valuable tool for early detection of functional decline because it includes, apart from a BADL subscale, another subscale containing a variety of instrumental activities of daily living (LADL), which are the first to be affected in dementing processes. We present an adaptation and validation of the IDDD for Spanish-speaking communities (S-IDDD). A total of 254 control subjects (CONT), 86 patients with mild memory/cognitive impairment with no dementia (CIND), and 111 patients diagnosed with probable dementia of the Alzheimer type (DAT) participated in this project. IDDD total scores (mean and SD) were as follow: CONT: 33.1 (0.4); CIND: 35.2 (3.4); DAT: 54.3 (18.6). The present validation showed no sociodemographic effects on the IDDD total scores. The IDDD demonstrated great internal consistency (alpha = .985) and reproducibility (intraclass correlation coefficient = .94). Correlations were high (r = .81; p < .1) when they took into account the whole sample, but decreased significantly when the groups were separated by pathologic condition. The scale showed significant differences between DAT versus CIND and CONT. The IADL subscale differentiated all three groups, which makes it extremely valuable for early detection of functional decline. The present study shows that the S-IDDD is a reliable adaptation of the original IDDD scale and may be used successfully in Spanish populations for staging and follow-up of subjects with dementia.

Activities of Daily Living↗
PubMed1997

The genotype 2/2 of the presenilin-1 polymorphism is decreased in Spanish early-onset Alzheimer's disease.

We have found a significantly lower frequency of the presenilin-1 (PS-1) intronic polymorphism 2/2 genotype in early-onset Alzheimer's disease (AD) patients without APOE epsilon4 alleles (2/2 = 0.054; P = 0.009) as compared to age matched non-epsilon4 controls (2/2 = 0.227). Moreover the average age of onset in AD patients with the PS-1 2/2 genotype is older than that in AD patients with a 1/2 genotype or with a 1/1 genotype. This data suggest a protective effect of the 2/2 genotype which would delay the age of onset in AD. Our results do not support an association between the 1/1 genotype and AD. However, a non-significant increase of the 1/1 genotype is found in non-epsilon4 AD patients (P = 0.20).

Age of Onset↗
PubMed1997

[Normalization of cognitive and functional assessment instruments for dementia (NORMACODEM) (I): objectives, content and population].

UNLABELLED: To adequately evaluate patients with 4 neuropsychological deficits a project for norming cognitive and functional instruments that assess dementia (NORMACODEM) was designed. Four hundred fifty-one subjects in three groups: 254 controls, 86 patients with minor memory/cognitive deficits without dementia (DWD) and 111 patients with probable Alzheimer-type dementia (ATD) according to the NINCDS/ADRDA criteria. Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale (ADAS), Abbreviated Barcelona Test (ABT), Global Dementia Staging (GDS), Functional Assessment Staging (FAST), Clinical Dementia Rating (CDR), Rapid Disability Rating Scale-2 (RDRS-2), Blessed Dementia Rating Scale (BDRS), Interview for Deterioration in Daily life in Dementia (IDDD), Geriatric Evaluation by Relatives Rating Instrument (GERRI), Geriatric Depression Scale (GDS), Zung Self-Rating Anxiety Scale (ZSRAS). Descriptive statistics and analysis of variance. The characteristics of the sample were as follows. CONTROLS: 99 men, 155 women. Mean (SD) age: 64.6 (10.9) years. Mean (SD) educational level: 9.1 (4.9) years. DWD: 42 men, 44 women. Mean (SD) age: 65.8 (8.7) years. Men (SD) educational level: 8.4 (4.4) years. ATD: 48 mean, 63 women. Mean (SD) age: 68.3 (8.0) years. Mean (SD) educational level: 6.2 (4.3) years. The ATD patients were significantly older than the controls. Mean educational level was significantly lower in the ATD group than in the other two.

Adult↗
PubMed1997

[Adaptation and normalization of the Alzheimer's disease Assessment Scale for Spain (NORMACODEM) (II)].

UNLABELLED: This report is part of a project for norming cognitive and functional instruments that assess dementia (NORMACODEM). To adapt and norm the Alzheimer's Disease Assessment Scale (ADAS) for use in Spain. Two hundred fifty-four controls, 86 patients with minor memory/cognitive disorders without dementia (deterioration without dementia, DWD), 111 patients with Alzheimer-type dementia (ATD). Statistical description. Multivariate linear regression. Crossed validation. Internal consistency and test-retest (n = 48). The mean scores (SD) obtained were as follows. CONTROLS: ADAS-Cog = 8.0 (3.4), ADAS-Noncog = 2.9 (2.9), ADAS-Tot = 10.9 (4.6). DWD: ADAS-Cog = 11.37 (5.1), ADAS-Noncog = 4.9 (4.3), ADAS-Tot = 16.2 (7.0). ATD: ADAS-Cog = 31.8 (5.1), ADAS-Noncog = 10.3 (4.3), ADAS-Tot = 42.2 (20.7). Multiple regression analysis revealed that educational level and age were significantly associated with the ADAS-Cog score. The internal consistency of the ADAS-Cog was 0.963. The test-retest procedure yielded linear correlation, coefficients of 0.93 for the ADAS-Cog, 0.86 for the ADAS-Noncog and 0.95 for the ADAS-Tot. Age and educational level/schooling are associated to the earned on the ADAS-Cog instrument. The present Spanish version of the ADAS has high internal consistency and reproducibility. The instruments can be use for assessment in Spanish populations.

Adult↗
PubMed1997

[Shortened version of the Barcelona test (III): criterion validity with the ADAS-Cog].

The aim of this study was to assess the criterion validity of a global score of an abbreviated version of the Barcelona Test (BTA), normalized for age and education, as a clinical neuropsychometric test for the assessment of cognitive impairment. This study made a correlational analysis between test scores of the BTA and scores of the cognitive part of the Alzheimer's Disease Assessment Scale (ADAS-Cog) adjusted for age and education. It was made in a University Hospital (Dementia Unit). A group of 172 subjects (74 male, 98 female) was distributed according the Global Deterioration Stages (GDS) from 1 to 6. GDS-1 (normal controls), n = 60; GDS-2 (subjective complaints), n = 27; GDS-3, n = 21, GDS-4, n = 22; GDS-5, n = 16; GDS 6, n = 26. All dementia patients fulfilled the NINCDS/ADRDA criteria. BTA global scores correlated significantly with adjusted scores on the ADAS-Cog (r = 0.872, r2 = 0.761), p < 0.0001. The BTA has a criterion validity as a clinical neuropsychometric test for the study of cognitive impairment.

Adult↗
PubMed1997

[PET and SPECT in Parkinson's disease].

Positron emission tomography (PET) with [18F] fluorodopa (FD) assesses nigrostriatal function in vivo. Measurements deriving from FD PET have direct lineal relationship to the nigral cell count in normal ageing and in Parkinson's disease (PD), although in PD the progression of the decline in nigrostriatal dopaminergic function is faster than the controls. The functional anatomy of the movements has been studied using PET and SPECT. The supplementary motor area (SMA) dysfunction is responsible for bradykinesia in Parkinson. The SMA is undereactive in PD during self-generated movements, and this underactivation is reversed by the administration of apomorphine and modulate by the stereotaxic ventral pallidotomy. PET has been used, also, to attempt the differentiation of PD, multiple system atrophy (MSA) and PSP, in vivo, using a number of different radioligands (opiod, dopamine receptor binding). [11C] raclopride PET and [123I] IBF SPECT seemed a promising agents to assessing D2 receptor status in humans. Studies of D2 status have demonstrated normal or increased D2 receptor density in PD and decreased receptor density in PSP and MSA. Using SPECT has been demonstrated marked differences of the DA transporters located on dopaminergic terminals in the striatum in healthy controls and PD patients. Also the correlation of SPECT measures of transporters of DA and motor severity suggests that this may be a useful marker of disease severity in PD.

Brain↗
PubMed1996

High apolipoprotein E epsilon 4 allele frequency in age-related memory decline.

Many studies have demonstrated a strong association between the presence of one or two epsilon 4 alleles and Alzheimer's disease (AD), although few data are available on the apolipoprotein E (APOE) epsilon 4 frequencies at the preclinical stages of AD. Thus, with a view to determining whether APOE genotyping could be useful in the early detection of AD, we determined the Apoe allele frequencies in patients with memory complaints without dementia (age-related memory decline, ARMD). We found an APOE epsilon 4 allele frequency of 0.315 in the ARMD group, similar to 0.293 in the AD group, in contrast to 0.057 in the control group. Significant differences (t=-2.91, df=25, p=0.008) were found between the Alzheimer's Disease Assessment Scale (ADAS) total scores in the ARMD patients with at least one epsilon 4 allele (mean=24.2) compared with the ARMD patients without the epsilon 4 allele (mean=14.7). Our results suggest that the patients with memory complaints, a high ADAS score, and the presence of one or two APOE-4 alleles could be at high risk for developing AD. Thus, we propose that genotyping in conjunction with the ADAS scale may prove useful as diagnostic markers of AD in the presymptomatic stages.

Aged↗
PubMed1995

Apolipoprotein E4 allele frequency in Spanish Alzheimer and control cases.

We have found an APOE epsilon 4 allelic frequency of 0.289 (95% CI 0.195-0.383) in Spanish AD patients (n = 88; average age = 71.2 +/- 9.37) and of 0.061 (95% CI 0.023-0.099) in age-matched controls (n = 147; average age = 71.5 +/- 10.29). Remarkably no ApoE 4/4 subjects were observed in any of the age-matched control groups compared to a total of 22 AD patients with the ApoE 4/4 phenotype. The combined odds ratio for subjects with one or two epsilon 4 alleles in the present study is 6.25 (95% CI 3.13-12.60), which is one of the highest so far reported. Altogether our results suggest a trans-European difference in the ApoE epsilon 4 frequency but no differences in the strength of the association between APOE4 and AD.

Adult↗
PubMed1995

Prevalence of multiple sclerosis in the region of Osona, Catalonia, northern Spain.

To ascertain the prevalence of multiple sclerosis in the region of Osona in Catalonia, northern Spain, an intensive study was undertaken in a small population of 72,000 people over a period of five years, using many sources of information. Patients were classified according to the Poser criteria. Most of the patients presented with mild symptoms only and many had not seen a neurologist or attended a large hospital. The prevalence of definite and probable multiple sclerosis was 58 per 100,000. This is nine to 10 times higher than had been found previously in Catalonia and is a similar prevalence to that found in southern Spain, in Sicily, and in Greek speaking Cyprus.

Adolescent↗
PubMed1994

Pharmacological evaluation of the cholinergic system in progressive supranuclear palsy.

Severe cholinergic loss occurs in the brains of patients with progressive supranuclear palsy. To evaluate the functional implications of this neuronal deficit, dose-response curves were obtained in patients with progressive supranuclear palsy and normal control subjects undergoing intravenous cholinergic blockade (scopolamine) and stimulation (physostigmine). Physostigmine had no significant neurobehavioral effects at any dose in patients with progressive supranuclear palsy. Scopolamine, at low and medium doses, significantly impaired memory performance of both groups, but worsened the gait of only the patients. High-dose scopolamine, which could not be tolerated by the patients, resulted in gait deterioration among control subjects. Thus, patients with progressive supranuclear palsy have increased sensitivity to cholinergic blockade compared to control subjects. Since loss of cholinergic neurons appears to contribute to the pathogenesis of certain cognitive and motor deficits found in progressive supranuclear palsy, the use of oral anticholinergics should ordinarily be avoided in this disorder. On the other hand, physostigmine at clinically tolerated dose levels seems to be therapeutically ineffective.

Aged↗