Use of Antipsychotics in Patients with Behavioral and Psychological Symptoms of Dementia: Results of a Spanish Delphi Consensus.

BACKGROUND: Behavioral and psychological symptoms of dementia (BPSD) are difficult to manage and associated with poor outcome. OBJECTIVES: The aim of this study was to reach consensus on the use of antipsychotics in patients with BPSD in Spain. METHODS: A qualitative, multicenter, two-round Delphi study was carried out, with the participation of specialists involved in the care of dementia patients throughout Spain. They completed a 76-item questionnaire related to the identification of BPSD, treatment with antipsychotics, follow-up of patients, barriers for the use of atypical antipsychotics, and effects of antipsychotics on quality of life. RESULTS: A total of 162 specialists in neurology, psychiatry, and geriatrics (61% men) with a mean (SD) age of 45.9 (10) years participated in the study. Almost all participants (96.9%) strongly agreed that atypical antipsychotics are safer and better tolerated than typical antipsychotics. There was agreement on the importance to review the indication and dose of the antipsychotic drug at least every 3 months. There was consistent high rate of agreement on the beneficial impact of atypical antipsychotics on the quality of life of patients with dementia and their caregivers. A consensus was also reached on the need of detecting BPSD in patients with dementia as it decreases the quality of life of both patients and caregivers, and the need to routinely screen for dementia in elderly patients with no previous psychiatric history in the presence of suggestive symptoms of BPSD. Finally, the participants in the study agreed that administrative barriers for the prescription of atypical antipsychotics in Spain hinder the access to this drug group and favor the prescription of typical antipsychotics. CONCLUSIONS: The participants in the study agreed that atypical antipsychotics should be preferred to typical antipsychotics in the management of BPSD. Wide consensus was reached about the importance of early identification of BPSD in persons with cognitive impairment, the use and management of atypical antipsychotic drugs and their favorable impact on patients and caregiver's quality of life.

Frecuente alteración de la vía amiloide en la demencia con cuerpos de Lewy prodrómica / Frequent involvement of the amyloid pathway in prodromal dementia with Lewy bodis

Introducción. La demencia con cuerpos de Lewy (DCLW) es la más frecuente de las degenerativas, después de la enfermedad de Alzheimer. Objetivo. Analizar los biomarcadores core de la enfermedad de Alzheimer en el líquido cefalorraquídeo de pacientes exclusivamente hispanos con DCLW prodrómica, para conocer si existe alteración de la vía amiloide o de la vía tau. Pacientes y métodos. Entre 2008-2017 incluimos a 430 pacientes con deterioro cognitivo leve según los criterios de Petersen, procedentes de tres hospitales de la provincia de Alicante. Se les realizaron revisiones clínicas cada 6-12 meses para evaluar su estabilidad clínica o la progresión a demencia utilizando los criterios clínicos vigentes. Entre otras pruebas complementarias se analizaron los biomarcadores de enfermedad de Alzheimer en el líquido cefalorraquídeo. Resultados. Entre todos los pacientes incluidos, 26 desarrollaron DCLW y 29 se mantuvieron estables durante al menos cinco años, por lo que los consideramos como referencia. En este grupo solamente cinco (17%) tenían valores de proteína Abeta(1-42) inferiores a la normalidad, mientras que 16 (55%) de los pacientes con DCLW tenían niveles alterados. No se encontraron diferencias en los niveles de las proteínas tau. Al comparar los grupos con DCLW con y sin amiloidosis solamente encontramos diferencias en los niveles de proteína Abeta(1-42). Conclusiones. Destacamos la frecuente presencia de patología amiloidea en la DCLW prodrómica en nuestra población y la probable alteración de diferentes vías metabólicas en una misma demencia clínicamente definida

Introduction. Lewy body dementia (LBD) is the most frequent of the degenerative dementias, after Alzheimer’s disease. Aim. To analyse the core biomarkers of Alzheimer’s disease in the cerebrospinal fluid of exclusively Hispanic patients with prodromal LBD, in order to determine whether there is involvement of the amyloid pathway or the tau pathway. Patients and methods. Between 2008 and 2017 we included 430 patients with mild cognitive impairment according to Petersen criteria, from three hospitals in the province of Alicante. They underwent clinical check-ups every 6-12 months to evaluate their clinical stability or their progression to dementia using current clinical criteria. Among other complementary tests, biomarkers for Alzheimer's disease in the cerebrospinal fluid were analysed. Results. Of all the patients included, 26 developed LBD and 29 remained stable for at least five years, and were thus considered as a reference. In this group only five (17%) had Aβ1-42 protein values below normal, whereas 16 (55%) of the patients with LBD had altered levels. No differences were found in the levels of tau protein. On comparing the LBD groups with and without amyloidosis, differences were only found in the levels of Aβ1-42 protein. Conclusions. We highlight the frequent presence of amyloid pathology in prodromal LBD in our population, and the probable involvement of different metabolic pathways in the same clinically defined dementia

Alzheimer's disease cerebrospinal fluid biomarker in cognitively normal subjects.

In a large multicentre sample of cognitively normal subjects, as a function of age, gender and APOE genotype, we studied the frequency of abnormal cerebrospinal fluid levels of Alzheimer's disease biomarkers including: total tau, phosphorylated tau and amyloid-ß1-42. Fifteen cohorts from 12 different centres with either enzyme-linked immunosorbent assays or Luminex® measurements were selected for this study. Each centre sent nine new cerebrospinal fluid aliquots that were used to measure total tau, phosphorylated tau and amyloid-ß1-42 in the Gothenburg laboratory. Seven centres showed a high correlation with the new Gothenburg measurements; therefore, 10 cohorts from these centres are included in the analyses here (1233 healthy control subjects, 40-84 years old). Amyloid-ß amyloid status (negative or positive) and neurodegeneration status (negative or positive) was established based on the pathological cerebrospinal fluid Alzheimer's disease cut-off values for cerebrospinal fluid amyloid-ß1-42 and total tau, respectively. While gender did not affect these biomarker values, APOE genotype modified the age-associated changes in cerebrospinal fluid biomarkers such that APOE ε4 carriers showed stronger age-related changes in cerebrospinal fluid phosphorylated tau, total tau and amyloid-ß1-42 values and APOE ε2 carriers showed the opposite effect. At 40 years of age, 76% of the subjects were classified as amyloid negative, neurodegeneration negative and their frequency decreased to 32% at 85 years. The amyloid-positive neurodegeneration-negative group remained stable. The amyloid-negative neurodegeneration-positive group frequency increased slowly from 1% at 44 years to 16% at 85 years, but its frequency was not affected by APOE genotype. The amyloid-positive neurodegeneration-positive frequency increased from 1% at 53 years to 28% at 85 years. Abnormally low cerebrospinal fluid amyloid-ß1-42 levels were already frequent in midlife and APOE genotype strongly affects the levels of cerebrospinal fluid amyloid-ß1-42, phosphorylated tau and total tau across the lifespan without influencing the frequency of subjects with suspected non-amyloid pathology.