Tirso Zúñiga-Santamaría

Background/Objectives: Several genetic factors are related to the risk of Alzheimer’s disease (AD) and the response to cholinesterase inhibitors (ChEIs) (donepezil, galantamine, and rivastigmine) or memantine. However, findings have been controversial, and, to the best of our knowledge, admixed populations have not been previously evaluated. We aimed to determine the impact of genetic and non-genetic factors on the risk of AD and the short-term response to ChEIs and memantine in patients with AD from Mexico. Methods: This study included 117 patients from two specialty hospitals in Mexico City, Mexico. We evaluated cognitive performance via clinical evaluations and neuropsychological tests. Nineteen variants in ABCB1, ACHE, APOE, BCHE, CHAT, CYP2D6, CYP3A5, CHRNA7, NR1I2, and POR were assessed through TaqMan assays or PCR. Results: Minor alleles of the ABCB1 rs1045642, ACHE rs17884589, and CHAT rs2177370 and rs3793790 variants were associated with the risk of AD; meanwhile, CHRNA7 rs6494223 and CYP3A5 rs776746 were identified as low-risk variants in AD. BCHE rs1803274 was associated with worse cognitive functioning. None of the genetic and non-genetic factors studied were associated with the response to pharmacological treatment. Conclusions: We identified potential genetic variants related to the risk of AD; meanwhile, no factor was observed to impact the response to pharmacological therapy in patients with AD from Mexico.

Comercialización de pruebas genéticas: un enfoque bioético

The number of older people is set to increase dramatically worldwide. Demographic changes are likely to result in the rise of age-related chronic diseases which largely contribute to years lived with a disability and future dependence. However dependence is much less studied although intrinsically linked to disability. We investigated the prevalence and correlates of dependence among older people from middle income countries. A one-phase cross-sectional survey was carried out at 11 sites in seven countries (urban sites in Cuba, Venezuela, and Dominican Republic, urban and rural sites in Peru, Mexico, China and India). All those aged 65 years and over living in geographically defined catchment areas were eligible. In all, 15,022 interviews were completed with an informant interview for each participant. The full 10/66 Dementia Research Group survey protocol was applied, including ascertainment of depression, dementia, physical impairments and self-reported diagnoses. Dependence was interviewer-rated based on a key informant's responses to a set of open-ended questions on the participant's needs for care. We estimated the prevalence of dependence and the independent contribution of underlying health conditions. Site-specific prevalence ratios were meta-analysed, and population attributable prevalence fractions (PAPF) calculated. The prevalence of dependence increased with age at all sites, with a tendency for the prevalence to be lower in men than in women. Age-standardised prevalence was lower in all sites than in the USA. Other than in rural China, dementia made the largest independent contribution to dependence, with a median PAPF of 34% (range 23%-59%). Other substantial contributors were limb impairment (9%, 1%-46%), stroke (8%, 2%-17%), and depression (8%, 1%-27%). The demographic and health transitions will lead to large and rapid increases in the numbers of dependent older people particularly in middle income countries (MIC). The prevention and control of chronic neurological and neuropsychiatric diseases and the development of long-term care policies and plans should be urgent priorities.

La relevancia del problema de salud pública que representan en el mundo las demencias, su asociación con la dependencia y el riesgo de maltrato en los ancianos con demencia por parte de sus cuidadores primarios o sus familiares, hacen necesario el análisis y la reflexión “de las implicaciones éticas, económicas, jurídicas, políticas y no sólo las consideraciones médicas”, de este problema, que reviste un interés particular dentro del campo de la Bioética. Se realizó una encuesta con el objetivo de determinar la dependencia física y detectar el maltrato, así como la asociación entre maltrato y respeto de sus preferencias en el anciano con demencia. Se evaluaron 61 ancianos con demencia de leve a moderada, de los cuales 73,8% fueron mujeres y 26,2% hombres. El porcentaje de pacientes que sufren maltrato fue de 29,2% en mujeres y 18,8% en hombres. No se encontró asociación estadísticamente signifi cativa entre maltrato y dependencia física. Sin embargo, se encontró un riesgo de maltrato de 47,30% en ancianos con demencia a quienes no se les respetan sus preferencias con respecto a quienes sí se le respetan, medida con signifi cancia estadística (IC 95%, 6,73-495,18).