[show abstract][hide abstract] ABSTRACT: Reduced uptake of (123)I- metaiodobenzylguanidine (MIBG) on cardiac gammagraphy and impaired odor identification are markers of neurodegenerative diseases with Lewy bodies (LB) as a pathological hallmark, such as idiopathic Parkinson's disease (IPD). LRRK2 patients present with a clinical syndrome indistinguishable from IPD, but LB have not been found in some cases. Patients with such mutations could behave differently than patients with IPD with respect to MIBG cardiac uptake and olfaction. We studied 14 LRRK2 patients, 14 IPD patients matched by age, gender, disease duration and severity, and 13 age and gender matched control subjects. Olfaction was analyzed through the University of Pennsylvania Smell Identification Test (UPSIT). MIBG cardiac uptake was evaluated through the H/M ratio. The late H/M was 1.44 ± 0.31 for LRRK2 patients, 1.19 ± 0.15 for PD patients, and 1.67 ± 0.16 for control subjects. LRRK2 patients presented lower but not statistically significant MIBG cardiac uptake than controls (p = 0.08) and significant higher uptake than PD patients (p = 0.04). UPSIT mean scores were 21.5 ± 7.3 for LRRK2 patients, 18.7 ± 6.2 for IPD patients and 29.7 ± 5.7 for control subjects. UPSIT score was lower in both LRRK2 and PD than in controls. In LRRK2 patients a positive correlation was found between myocardial MIBG uptake and UPSIT scores, (R = 0.801, p < 0.001). In LRRK2 patients, MIBG cardiac uptake was less impaired than in PD; a positive correlation between MIBG cardiac uptake and UPSIT scores was observed. As MIBG cardiac reduced uptake and impaired odor identification are markers of LB pathology, this findings may represent neuropathological heterogeneity among LRRK2 patients.
Journal of Neurology 01/2011; 258(6):1126-32. · 3.58 Impact Factor
[show abstract][hide abstract] ABSTRACT: Autosomal dominant early-onset Alzheimer disease is a heterogeneous condition that has been associated with mutations in 3 different genes: the amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2) genes. Most cases are due to mutations in the PSEN1 gene, whereas mutations in the APP and PSEN2 genes are rare.
To describe a novel mutation in the PSEN2 gene associated with early-onset autosomal dominant Alzheimer disease.
The proband was a 49-year-old individual who displayed progressive dementia beginning at age 45 years. One of the parents and one of the grandparents had developed dementia at ages 64 years and 60 years, respectively, and 1 sibling had mild cognitive impairment. Some family members also had Tourette syndrome. Mutation analysis of the APP, PSEN1, PSEN2, and tau (TAU) genes was performed. Apolipoprotein E (APOE) was also genotyped.
We found a missense mutation at codon 430 of the PSEN2 gene that predicts a threonine-to-methionine substitution. This mutation was detected in the affected individuals and in 1 cognitively healthy sibling. The mutation was absent in 260 control chromosomes. The normal amino acid was conserved in the human and mouse PSEN1 and mouse PSEN2 homologues. No influence of the APOE genotype was observed.
We have found a novel mutation in the PSEN2 gene in a family with early-onset Alzheimer disease. The variation in the age at onset confirms that PSEN2 mutations are associated with variable clinical expression.
[show abstract][hide abstract] ABSTRACT: The Mini-Mental State (MMS) is a brief structured test of cognitive function. The purpose of this study was to adapt and normalise MMS for the Spanish population. The test was administered to 450 subjects (253 control volunteers, 86 mild memory/cognitive impairment without dementia subjects - CIWD and 111 Alzheimer's Disease patients - AD). A cross-sectional statistical study in a population stratified by age and education was conducted. A more accurate diagnosis is provided by scores that have been adjusted for age and level of education. The recommended cut-off in our study was 24/25 (non-demented above 24). The adaptation and normalisation of MMS provides the Spanish population with a highly valuable screening tool.
[show abstract][hide abstract] ABSTRACT: To measure the sleep spindle characteristics in patients with unilateral thalamic stroke.
A prospective study of patients with thalamic stroke and age-matched healthy controls.
Department of Neurology of a University Hospital.
Thirteen patients (mean age: 67 years, SD: 13,44) with an isolated, unilateral acute thalamic stroke and 18 healthy age-matched volunteers.
A polysomnogram recording from 14 scalp EEG electrodes performed during 2 consecutive nights, the second or third week after the stroke. Only the sleep of the second night was analyzed.
Sleep spindles were counted during two separate 10-minute epochs of stage II. Spindles appearing synchronously in both sides with similar amplitude were called "bilateral." Spindles with twice the amplitude in one side than the other were "right" or "left-side predominant". There were 8 patients with posterolateral, 3 with global and 2 with anterior lesions. Eight were right and 5 left-sided. The number of spindles was similar in patients (39.8 +/- 23.4 in 20 minutes) than controls (26.07 +/- 29.07; p=0.173). Spindles with a centroparietal (34%) and centroparieto-occipital localization (22%) were the most frequent. In controls approximately 66% of the spindles had a bilateral and symmetric distribution over the scalp, 23% of the spindles were predominantly left-sided and 5% were predominantly right-sided. In patients, bilateral spindles decreased (p<0.0001) but asymmetric spindles did not change.
Unilateral acute thalamic stroke does not decrease sleep spindles ipsilaterally; rather, it seems to produce a bilateral diminution in their number.
[show abstract][hide abstract] ABSTRACT: Corticobasal degeneration syndrome (CBDS) is a well-described entity, although there are some cases in which clinical manifestations do not link with pathological findings. We present a 60-year-old man with a clinical course of CBDS. Postmortem examination demonstrated the features of the Lewy body variant of Alzheimer disease (LBVA). Different neurological evaluations showed a progressive motor disorder with alien hand and parkinsonism affecting mainly the left side. His neuropsychological examination was comparable with biparietal dysfunction, especially apraxias and signs of Gertsmann's syndrome. MRI and SPECT imaging revealed parietal, temporal and occipital involvement. We conclude that the CBDS is a heterogeneous pathological entity.
International Journal of Geriatric Psychiatry 12/1998; 11(6):559 - 564. · 2.98 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.
[show abstract][hide abstract] ABSTRACT: 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.
[show abstract][hide abstract] ABSTRACT: 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.
Annals of Neurology 05/1996; 39(4):548-51. · 11.19 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.