Uso de antipsicóticos en los pacientes con demencia en España: comparación con la prescripción de los inhibidores de la acetilcolinesterasa y de la memantina, y análisis de las asociaciones / Use of antipsychotics in patients with dementia in Spain: Comparison with prescription of acetylcholinesterase inhibitors and memantine and analysis of associations

Objetivo: Se ha analizado la prevalencia de antipsicóticos, inhibidores de la acetilcolinesterasa (IACE) y memantina en pacientes con demencia en España y la influencia de estas asociaciones en su prescripción. Método: Estudio descriptivo, retrospectivo y transversal de la base BIFAP de 2017 en los mayores de 65 años con demencia. Se recogieron las prescripciones de antipsicóticos, los IACE y la memantina. Para los antipsicóticos también se recogieron, la duración del tratamiento y el tiempo desde el diagnóstico de demencia, al de prescripción. Resultados: Se recuperaron 1.327.792 sujetos, 89.464 (6,73%) con demencia. El 31,76% tuvieron prescritos antipsicóticos; los más frecuentes: quetiapina (58,47%), risperidona (21%) y haloperidol (19,34%). Las prescripciones de IACE y memantina fueron más frecuentes en los menores de 84 años y las de antipsicóticos en los mayores de 85 años (p<0,001). Los antipsicóticos se mantuvieron una media de 1.174,5 días. En el 26,4% de los casos se prescribieron aislados, OR: 0,61 (IC 95%: 0,59-0,62), en el 35,85% asociados a IACE, OR: 1,26 (IC 95%: 1,22-1,30) y en el 42,4% a memantina, OR: 1,69 (IC 95%: 1,62-1,78); p<0,000). Desde el diagnóstico de demencia transcurrieron de 461 días (±1.576,5) cuando se prescribieron aislados; 651 días (±1.574,25) asociados a IACE y 1.224 (±1.779) a memantina. Conclusiones: Una tercera parte de los pacientes con demencia tuvieron prescritos antipsicóticos, mayoritariamente atípicos, más frecuentemente en los mayores de 85 años y durante periodos prolongados. La prescripción de IACE y memantina se asoció al incremento del riesgo de uso de antipsicóticos, pero paradójicamente, a la prolongación del tiempo hasta su prescripción.(AU)

ObjectiveWe have analyzed the prevalence of antipsychotics in patients with dementia in Spain, their age distribution and the influence of treatment with IACEs and memantine on their prescription. Method: Descriptive, retrospective and cross-sectional study of the 2017 BIFAP database in over 65 years of age with dementia. Prescriptions of antipsychotics, IACEs and memantine were collected. For antipsychotics were also collected, the duration of treatment and time from dementia diagnosis to prescription. Results: A total of 1,327,792 subjects were retrieved, 89,464 (6.73%) with dementia. Antipsychotics were prescribed in 31.76%; by frequency: quetiapine (58.47%), risperidone (21%) and haloperidol (19.34%). Prescriptions of IACEs and memantine were clustered in those younger than 84 years and antipsychotics in those older than 85 (P<.001). Antipsychotics were maintained for a mean of 1174.5 days. In 26.4% of cases they were prescribed alone, OR 0.61 (95% CI: 0.59-0.62), in 35.85% associated with IACEs, OR 1.26 (95% CI: 1.22-1.30) and in 42.4% with memantine, OR 1.69 (95% CI: 1.62-1.78) (P<.000). From the diagnosis of dementia, 461 days (±1576.5) elapsed when isolated drugs were prescribed; 651 days (±1574.25) associated with IACEs and 1224 (±1779) with memantine. Conclusions: One third of patients with dementia were prescribed antipsychotics, mostly atypical, more frequently in those older than 85 years and for prolonged periods. IACEs and memantine were associated with the risk of antipsychotic prescription, but paradoxically, with prolonged time to onset.(AU)

Biomarkers in Alzheimer's Disease: Are Olfactory Neuronal Precursors Useful for Antemortem Biomarker Research?

Alzheimer's disease (AD), as the main cause of dementia, affects millions of people around the world, whose diagnosis is based mainly on clinical criteria. Unfortunately, the diagnosis is obtained very late, when the neurodegenerative damage is significant for most patients. Therefore, the exhaustive study of biomarkers is indispensable for diagnostic, prognostic, and even follow-up support. AD is a multifactorial disease, and knowing its underlying pathological mechanisms is crucial to propose new and valuable biomarkers. In this review, we summarize some of the main biomarkers described in AD, which have been evaluated mainly by imaging studies in cerebrospinal fluid and blood samples. Furthermore, we describe and propose neuronal precursors derived from the olfactory neuroepithelium as a potential resource to evaluate some of the widely known biomarkers of AD and to gear toward searching for new biomarkers. These neuronal lineage cells, which can be obtained directly from patients through a non-invasive and outpatient procedure, display several characteristics that validate them as a surrogate model to study the central nervous system, allowing the analysis of AD pathophysiological processes. Moreover, the ease of obtaining and harvesting endows them as an accessible and powerful resource to evaluate biomarkers in clinical practice.

[Use of antipsychotics in patients with dementia in Spain: Comparison with prescription of acetylcholinesterase inhibitors and memantine and analysis of associations]. / Uso de antipsicóticos en los pacientes con demencia en España: comparación con la prescripción de los inhibidores de la acetilcolinesterasa y de la memantina, y análisis de las asociaciones.

OBJECTIVE: We have analyzed the prevalence of antipsychotics in patients with dementia in Spain, their age distribution and the influence of treatment with IACEs and memantine on their prescription. METHOD: Descriptive, retrospective and cross-sectional study of the 2017 BIFAP database in over 65 years of age with dementia. Prescriptions of antipsychotics, IACEs and memantine were collected. For antipsychotics were also collected, the duration of treatment and time from dementia diagnosis to prescription. RESULTS: A total of 1,327,792 subjects were retrieved, 89,464 (6.73%) with dementia. Antipsychotics were prescribed in 31.76%; by frequency: quetiapine (58.47%), risperidone (21%) and haloperidol (19.34%). Prescriptions of IACEs and memantine were clustered in those younger than 84 years and antipsychotics in those older than 85 (P<.001). Antipsychotics were maintained for a mean of 1174.5 days. In 26.4% of cases they were prescribed alone, OR 0.61 (95% CI: 0.59-0.62), in 35.85% associated with IACEs, OR 1.26 (95% CI: 1.22-1.30) and in 42.4% with memantine, OR 1.69 (95% CI: 1.62-1.78) (P<.000). From the diagnosis of dementia, 461 days (±1576.5) elapsed when isolated drugs were prescribed; 651 days (±1574.25) associated with IACEs and 1224 (±1779) with memantine. CONCLUSIONS: One third of patients with dementia were prescribed antipsychotics, mostly atypical, more frequently in those older than 85 years and for prolonged periods. IACEs and memantine were associated with the risk of antipsychotic prescription, but paradoxically, with prolonged time to onset.

Adherence to the Mediterranean diet and waist-to-hip ratio in middle-aged postmenopausal women are the main factors associated with semantic verbal fluency 12 years later.

Few studies have analized the effect of vascular risk factors and lifestyle habits affecting the middle age of postmenopausal women on later cognitive performance in old age. We have carried out an observational study to identify those factors and whether they differ from those acting in men. Postmenopausal women and males, both aged 40-60 years old at recruitment, from a community dwelling cohort were included. Data for this study were collected from the first visit at recruitment (2001 to 2005). Participants were interviewed with a questionnaire on their health-related antecedents and underwent a physical exam. The cohort was contacted again for a new presential visit between 2014 and 2015. A semantic verbal fluency test was included in this new visit protocol as a brief measure of cognition. Besides educational attainment, Mediterranean diet adherence 20th percentile (OR = 1.93; 95%CI = 1.07-3.47) and waist to hip ratio 80th percentile (OR = 1.81; 95%CI = 1.10-2,98) were the main factors associated to low semantic fluency performance in postmenopausal women, while declared diabetes mellitus (OR = 2.24; 95%CI = 1.16-4,33), HOMA 2 insulin resistance index (OR = 1.77; 95%CI =1.04-3,02), light physical activity in leisure time (OR = 0.41; 95%CI = 0.19-0,93) and recommended moderate to vigorous physical activity (OR = 2.09; 95%CI = 1.23-3.56) did in men. Factors in middle age that explain semantic verbal fluency in old age are different between postmenopausal women and men. Menopause related fat redistribution may be a precondition for other vascular risk factors. The effect of Mediterranean diet on cognition deserves new specific studies centered on postmenopausal women as group.

[Prescription of acetylcholinesterase inhibitors and memantine in the Canary Islands, comparison with the Spanish population.] / Prescripción de inhibidores de acetilcolinesterasa y memantina en Canarias: comparación con la población española.

OBJECTIVE: In the Canary Islands the prescriptions billed to the National Health System are registered in a database (FarmaCanarias). The main objective was to estimate the consumption of Acetylcholinesterase inhibitors (IACE) and Memantine in Canary Islands and to compare with a Spanish sample from Pharmacoepidemiological Research Base in Primary Care (PRBPC) which is national in scope. As secondary we determined the percentage in treatment in the Spanish sample. METHODS: The prescriptions of IACE and / or memantine in 2017 were calculated as Defined Daily Doses per 100 habitants (DHD) in FarmaCanarias and PRBPC. The prescriptions in FarmaCanarias were disclosed by island and age groups were also compared. The percentage of cases in treatment was calculated in PRBPC from records with diagnosis of "dementia". All the comparations were made by Pearson's χ2. RESULTS: The prescription of IACE and Memantine was: 3.042% (95% CI; 3.039-3.045) and 1.584% (95% CI; 1.582-1.587) in The Canary islands, respectively and 2.545% (95% CI; 2.518-2.572) and 0.922% (95% CI; 0.906-0.938), in PRBPC (p<0.001). DHDs between islands were different, except in two (p<0.001) The distribution by age group between FarmaCanarias and PRBPC was hetereogeneous (p<0.001). The percentage of dementia cases in treatment in PRBPC was 45.51% (95% CI; 45.186-45.838). CONCLUSIONS: The prescription of IACE and Memantine was higher in the Canary Islands, which added to the difference by age group, suggests epidemiological differences in dementia compared to the mainland. There is heterogeneity between islands that could be due to epidemiological factors, provider or the Public Health Service.

OBJETIVO: En Canarias las recetas facturadas al Sistema Nacional de Salud están registradas en una base de datos (FarmaCanarias). El objetivo principal de este estudio fue calcular el consumo de inhibidores de la acetilcolinesterasa (IACE) y memantina en Canarias y compararlo con una muestra representativa de la población española procedente de la Base de Investigación Farmacoepidemiológica en Atención Primaria (BIFAP). Como objetivo secundario determinamos el porcentaje de casos tratados en la muestra española. METODOS: Las prescripciones de IACE y/o memantina se calcularon como Dosis Diarias Definidas por 100 habitantes (DHD) en FarmaCanarias y en BIFAP. Se calcularon los resultados por isla y también se compararon por grupos de edad. Los casos tratados se calcularon como porcentaje sobre los casos con demencia totales en BIFAP. Todas las comparaciones fueron efectuadas con la χ2 de Pearson. RESULTADOS: El consumo de IACE y Memantina fue de 3,042% (IC 95%; 3,039-3,045) y 1,584% (IC 95%; 1,582-1,587) en Canarias, respectivamente y de 2,545% (IC 95%; 2,518-2,572) y 0,922% (IC 95%; 0,906-0,938), en BIFAP (p<0,001). Las DHD entre islas fueron diferentes, salvo en dos (p<0,001). La distribución por grupos de edad entre FarmaCanarias y BIFAP fue heterogénea (p<0,001). El porcentaje de casos tratados en BIFAP fue: 45,51% (IC 95%; 45,186-45,838). CONCLUSIONES: La prescripción de IACE y Memantina fue mayor en Canarias lo que, añadido a la diferencia por grupos de edad, sugiere diferencias epidemiológicas en demencia frente al resto de España. Existe heterogeneidad entre islas que podría deberse a factores epidemiológicos, de proveedor o del Servicio Público de Salud.

A Real-Time Clinical Decision Support System, for Mild Cognitive Impairment Detection, Based on a Hybrid Neural Architecture.

Clinical procedure for mild cognitive impairment (MCI) is mainly based on clinical records and short cognitive tests. However, low suspicion and difficulties in understanding test cut-offs make diagnostic accuracy being low, particularly in primary care. Artificial neural networks (ANNs) are suitable to design computed aided diagnostic systems because of their features of generating relationships between variables and their learning capability. The main aim pursued in that work is to explore the ability of a hybrid ANN-based system in order to provide a tool to assist in the clinical decision-making that facilitates a reliable MCI estimate. The model is designed to work with variables usually available in primary care, including Minimental Status Examination (MMSE), Functional Assessment Questionnaire (FAQ), Geriatric Depression Scale (GDS), age, and years of education. It will be useful in any clinical setting. Other important goal of our study is to compare the diagnostic rendering of ANN-based system and clinical physicians. A sample of 128 MCI subjects and 203 controls was selected from the Alzheimer's Disease Neuroimaging Initiative (ADNI). The ANN-based system found the optimal variable combination, being AUC, sensitivity, specificity, and clinical utility index (CUI) calculated. The ANN results were compared with those from medical experts which include two family physicians, a neurologist, and a geriatrician. The optimal ANN model reached an AUC of 95.2%, with a sensitivity of 90.0% and a specificity of 84.78% and was based on MMSE, FAQ, and age inputs. As a whole, physician performance achieved a sensitivity of 46.66% and a specificity of 91.3%. CUIs were also better for the ANN model. The proposed ANN system reaches excellent diagnostic accuracy although it is based only on common clinical tests. These results suggest that the system is especially suitable for primary care implementation, aiding physicians work with cognitive impairment suspicions.

Expanding the phenotypic and molecular spectrum of RNA polymerase III-related leukodystrophy.

OBJECTIVE: To expand the phenotypic spectrum of severity of POLR3-related leukodystrophy and identify genotype-phenotype correlations through study of patients with extremely severe phenotypes. METHODS: We performed an international cross-sectional study on patients with genetically proven POLR3-related leukodystrophy and atypical phenotypes to identify 6 children, 3 males and 3 females, with an extremely severe phenotype compared with that typically reported. Clinical, radiologic, and molecular features were evaluated for all patients, and functional and neuropathologic studies were performed on 1 patient. RESULTS: Each patient presented between 1 and 3 months of age with failure to thrive, severe dysphagia, and developmental delay. Four of the 6 children died before age 3 years. MRI of all patients revealed a novel pattern with atypical characteristics, including progressive basal ganglia and thalami abnormalities. Neuropathologic studies revealed patchy areas of decreased myelin in the cerebral hemispheres, cerebellum, brainstem, and spinal cord, with astrocytic gliosis in the white matter and microglial activation. Cellular vacuolization was observed in the thalamus and basal ganglia, and neuronal loss was evident in the putamen and caudate. Genotypic similarities were also present between all 6 patients, with one allele containing a POLR3A variant causing a premature stop codon and the other containing a specific intronic splicing variant (c.1771-7C>G), which produces 2 aberrant transcripts along with some wild-type transcript. CONCLUSIONS: We describe genotype-phenotype correlations at the extreme end of severity of the POLR3-related leukodystrophy spectrum and shed light on the complex disease pathophysiology.