Alberto Bergareche

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

BackgroundThis study describes the prevalence of dementia and major dementia subtypes in Spanish elderly.MethodsWe identified screening surveys, both published and unpublished, in Spanish populations, which fulfilled specific quality criteria and targeted prevalence of dementia in populations aged 70 years and above.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.ResultsThe 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 Alzheimers 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 Alzheimers 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.ConclusionPrevalence of dementia and Alzheimers 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 Alzheimers 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 Parkinson’s disease and other types of Parkinsonism

Abstract.Objectives:To assess the prevalence of Parkinson’s disease and parkinsonism in two Spanish populations (Irun and Hondarribia, Bidasoa Region) and to compare the results with those of similar surveys.Methods:The survey included 2000 participants aged 65 years or older in a door-to-door, three-phase design. In the screening phase we used the SNES (Sicilian Neuro-Epidemiologic Study) screening questionnaire, which has 100% sensitivity. In phases 2 and 3 we carried out a 3-year follow-up of all cases diagnosed with parkinsonism in phase 2. Progressively stricter diagnostic criteria were chosen in order to minimize the impact of false positives on the final results.Results:The prevalence of Parkinson’s disease (PD) was 1.5 % (95% confidence interval, 0.9 to 2.3) and the prevalence of other types of parkinsonism (OP) was 1.1 % (95% confidence interval 0.6 to 1.9). The overall prevalence by age group was 0.4 % (65–74 years), 4.7% (75–84 years), and 2.9% (≥ 85 years) for Parkinson’s disease and 0.7%, 2%, and 3.9 % for parkinsonism, respectively. The other parkinsonism prevalence was 1.3 % in men and 1.6 % in women.Conclusions:These prevalence rates are similar than those found in studies made in other European countries. The prevalence of both Parkinson’s disease and other types of parkinsonism increased with age, with no significant differences between men and women.

Mutations in Progranulin Gene: Clinical, Pathological, and Ribonucleic Acid Expression Findings

BACKGROUND There is an increasing interest in the clinico-pathological correlation of mutations in progranulin (PGRN) and frontotemporal lobar degeneration (FTLD) complex diseases. We aim to study the PGRN expression variability in patients with different clinical features for a better understanding of its roles in FTLD disease. METHODS We sequenced the PGRN gene in 72 patients suffering from FTLD (25 familial and 47 sporadic cases) and in 24 asymptomatic at-risk relatives. We also analyzed PGRN expression in blood by quantitative real-time polymerase chain reaction from 37 patients, 8 asymptomatic mutation carriers, and 10 control subjects as well as in brain tissue from 16 patients and 9 control subjects. RESULTS Four novel mutations were associated with familial and sporadic FTLD and familial dementia associated with amyotrophic lateral sclerosis. We identified a close association between the IVS6-1G>A mutation in PGRN and corticobasal syndrome. Brain tissue was available for carriers of two of the four mutations (IVS6-1 G>A and P357HfsX3). Immunohistochemical analysis revealed ubiquitin- and TDP-43positive and tau/alpha-synuclein negative immunoreactive neuronal intranuclear inclusions. The relative expression of PGRN in the clinical sample was significantly lower in carriers of the IVS6-1 G>A than in control subjects. CONCLUSIONS Progranulopathies are a major cause of the main phenotypes included in the FTLD complex. According to our results, the level of expression of PGRN in blood could be a useful marker both for diagnostics of part of the spectrum of FTLD conditions and for monitoring future treatments that might boost the level of PGRN in this disorder.

Olfactory deficits and cardiac 123I‐MIBG in Parkinson's disease related to the LRRK2 R1441G and G2019S mutations

It has been proposed that olfactory tests and metaiodobenzylguanidine cardiac scintigraphy may help diagnose idiopathic Parkinsons disease in the premotor phase. However, it is not clear what value these tests have in all patients with Parkinsons disease and, particularly, in those who carry mutations in LRRK2. The objective was to analyze olfactory dysfunction and the changes in cardiac I‐metaiodobenzylguanidine uptake in patients with Parkinsons disease carrying the R1441G and G2019S mutations in LRRK2, and in patients with Parkinsons disease with no known mutations. Patients with Parkinsons disease were screened for R1441G and G2019S LRRK2 gene mutations and classified as LRRK2 mutation carriers or noncarriers. A total of 190 patients with Parkinsons disease (44 LRRK2 mutation carriers) were tested for olfactory dysfunction using the Brief Smell Identification Test. Cardiac 123I‐metaiodobenzylguanidine scintigraphy was performed on 90 patients with Parkinsons disease (27 LRRK2 mutation carriers). Thirty‐six percent of patients with LRRK2 mutations have hyposmia, compared to 75% of noncarrier patients with Parkinsons disease (P < .001). Sixty‐six percent of LRRK2 mutation carriers have low early metaiodobenzylguanidine uptake, compared to 86% of noncarriers (P = .048). Similarly, the heart/mediastinum ratio in delayed metaiodobenzylguanidine images appeared to differ between these groups of patients with Parkinsons disease, although these results did not reach statistical significance. The data obtained indicate that olfactory and cardiac impairment is less prevalent when Parkinsons disease is associated with mutations in LRRK2, although the underlying mechanisms for this difference remain unclear. Thus, such screening would be less useful to detect the premotor phase in asymptomatic relatives who carry mutations in LRRK2 than in cases not associated with LRRK2.

The validity of Hodkinson's Abbreviated Mental Test for dementia screening in Guipuzcoa, Spain

The objective of this research was to evaluate the validity of Hodkinson’s Abbreviated Mental Test (AMT) in screening for dementia and to identify the optimum cut‐off point to use in a prevalence survey. The study included two groups of persons: (i) a random sample of 183 individuals selected from census data, 96 of whom completed the study and (ii) another 36 persons with dementia were selected from a hospital outpatients department by sampling consecutive cases. The DSM‐IV criteria were used as the ‘gold standard’ to establish a diagnosis of dementia. The AMT was administered to the 132 participants who subsequently underwent independent clinical evaluation. In the community sample, 11 persons were diagnosed with dementia and 85 without. In the total sample, a score of 7 maximizes the efficacy of the test. The sensitivity for this cut‐off point is 91.5% (78.7–97.2%) and the specificity is 82.4% (72.2–89.5%). A score of 9 gives 100% sensitivity, but the proportion of false positives rises to 66%. Our results are consistent with other studies and suggest that the AMT is a valid instrument for use in screening for dementia in populations similar to the one in this study.

Dementia, stroke and Parkinson's disease in spanish populations: A review of door-to-door prevalence surveys

We identified 14 door-to-door prevalence surveys on dementia, parkinsonism or stroke in Spanish populations fulfilling specific criteria and combined selected age- and sex-specific data using logistic regression and taking Pamplona as a reference. The prevalence of dementia and of Alzheimer’s disease varied significantly with space. However, the largest variation was seen for vascular dementia: odds ratio (OR) and 95% confidence interval (CI) for Gerona were 6.42 (3.23–12.3) in women and 2.30 (1.10–4.79) in men. Stroke was particularly frequent among Arevalo’s women, with OR 2.10 and 95% CI 1.26–3.49. The prevalence of Parkinson’s disease was twofold higher in Cantalejo. Although differences in methodology make the interpretation of results problematic, the prevalence of stroke and vascular dementia in Spain seems to vary spatially, indicating a space for prevention.

Stroke prevalence among the Spanish elderly: an analysis based on screening surveys

BackgroundThis study sought to describe stroke prevalence in Spanish elderly populations and compare it against that of other European countries.MethodsWe identified screening surveys -both published and unpublished- in Spanish populations, which fulfilled specific quality requirements and targeted prevalence of stroke in populations aged 70 years and over. Surveys covering seven geographically different populations with prevalence years in the period 1991–2002 were selected, and the respective authors were then asked to provide descriptions of the methodology and raw age-specific data by completing a questionnaire. In addition, five reported screening surveys in European populations furnished useful data for comparison purposes. Prevalence data were combined, using direct adjustment and logistic regression.ResultsThe overall study population, resident in central and north-eastern Spain, totalled 10,647 persons and yielded 715 cases. Age-adjusted prevalences, using the European standard population, were 7.3% for men, 5.6% for women, and 6.4% for both sexes. Prevalence was significantly lower in women, OR 0.79 95% CI 0.68–0.93, increased with age, particularly among women, and displayed a threefold spatial variation with statistically significant differences. Prevalences were highest, 8.7%, in suburban, and lowest, 3.8%, in rural populations. Compared to pooled Spanish populations, statistically significant differences were seen in eight Italian populations, OR 1.39 95%CI (1.18–1.64), and in Kungsholmen, Sweden, OR 0.40 95%CI (0.27–0.58).ConclusionPrevalence in central and north-eastern Spain is higher in males and in suburban areas, and displays a threefold geographic variation, with women constituting the majority of elderly stroke sufferers. Compared to reported European data, stroke prevalence in Spain can be said to be medium and presents similar age- and sex-specific traits.

Prevalence of disability in a composite ≥75 year-old population in Spain: A screening survey based on the International Classification of Functioning

BackgroundThe prevalence and predictors of functional status and disability of elderly people have been studied in several European countries including Spain. However, there has been no population-based study incorporating the International Classification of Functioning, Disability and Health (ICF) framework as the basis for assessing disability. The present study reports prevalence rates for mild, moderate, and severe/extreme disability by the domains of activities and participation of the ICF.MethodsNine populations surveyed in previous prevalence studies contributed probabilistic and geographically defined samples in June 2005. The study sample was composed of 503 subjects aged ≥75 years. We implemented a two-phase screening design using the MMSE and the World Health Organization-Disability Assessment Schedule 2nd edition (WHO-DAS II, 12 items) as cognitive and disability screening tools, respectively. Participants scoring within the positive range of the disability screening were administered the full WHO-DAS II (36 items; score range: 0-100) assessing the following areas: Understanding and communication, Getting along with people, Life activities, Getting around, Participation in society, and Self-care. Each disability area assessed by WHO-DAS II (36 items) was reported according to the ICF severity ranges (No problem, 0-4; Mild disability, 5-24; Moderate disability, 25-49; Severe/Extreme disability, 50-100).ResultsThe age-adjusted disability prevalence figures were: 39.17 ± 2.18%, 15.31 ± 1.61%, and 10.14 ± 1.35% for mild, moderate, and severe/extreme disability, respectively. Severe and extreme disability prevalence in mobility and life activities was three times higher than the average, and highest among women. Sex variations were minimal, although life activities for women of 85 years and over had more severe/extreme disability as compared to men (OR = 5.15 95% CI 3.19-8.32).ConclusionsDisability is highly prevalent among the Spanish elderly. Sex- and age-specific variations of disability are associated with particular disability domains.

Prevalence of Essential Tremor: A Door-to-Door Survey in Bidasoa, Spain

Objectives: To assess the prevalence of essential tremor (ET) in two Spanish populations (Irun and Hondarribia, Bidasoa region) and to compare the results with those of similar surveys. Methods: The survey included 2,000 participants aged 65 years or older in a door-to-door, two-phase design. ET was defined as postural or kinetic tremor of the head or limbs. Results: ET prevalence after age adjustment was 4.8% (95% confidence interval, 3.6–6.4). Prevalence increased significantly with age and there were no sex differences. Conclusions: The age-adjusted prevalence rate of ET in people 65 years old and older in Bidasoa, Spain, is close to those described in other studies using a similar design and suggest no geographical variation. ET prevalence increases with age and has a similar distribution in males and females.

Penetrance in Parkinson's disease related to the LRRK2 R1441G mutation in the Basque country (Spain)†

The LRRK2 R1441G mutation was first identified in Basque families and it is responsible for 46% of familial Parkinsons disease (PD) and for 2.5% of sporadic PD in the PD population of Basque ascent. The aim of this study was to determine LRRK2 R1441G penetrance in PD in the Basque Country (Spain) to help in a more accurate genetic counseling. A total of 59 sibships containing 244 individuals, with a total of 40 PD‐affected relatives, were studied. Genetic testing for the R1441G mutation in the LRRK2 gene was performed in 133 individuals and was positive in 51% of them. Lifetime penetrance of R1441G mutations turned out to be 12.5% at 65 years to 83.4% at 80 years. No gender differences were found in penetrance.