Genomic Characterization of Host Factors Related to SARS-CoV-2 Infection in People with Dementia and Control Populations: The GR@ACE/DEGESCO Study.

Emerging studies have suggested several chromosomal regions as potential host genetic factors involved in the susceptibility to SARS-CoV-2 infection and disease outcome. We nested a COVID-19 genome-wide association study using the GR@ACE/DEGESCO study, searching for susceptibility factors associated with COVID-19 disease. To this end, we compared 221 COVID-19 confirmed cases with 17,035 individuals in whom the COVID-19 disease status was unknown. Then, we performed a meta-analysis with the publicly available data from the COVID-19 Host Genetics Initiative. Because the APOE locus has been suggested as a potential modifier of COVID-19 disease, we added sensitivity analyses stratifying by dementia status or by disease severity. We confirmed the existence of the 3p21.31 region (LZTFL1, SLC6A20) implicated in the susceptibility to SARS-CoV-2 infection and TYK2 gene might be involved in COVID-19 severity. Nevertheless, no statistically significant association was observed in the COVID-19 fatal outcome or in the stratified analyses (dementia-only and non-dementia strata) for the APOE locus not supporting its involvement in SARS-CoV-2 pathobiology or COVID-19 prognosis.

Common variants in Alzheimer's disease and risk stratification by polygenic risk scores.

Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease.

Study of community-living Alzheimer's patients' adherence to the Mediterranean diet and risks of malnutrition at different disease stages.

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disease that is characterized by deficits in episodic memory. It is the most common form of dementia and affects 50-70% of patients with cognitive impairments over the age of 65. Elderly people are particularly susceptible to malnutrition and that risk is even higher in patients with AD. This study assessed the nutritional status of patients with AD at different stages of AD and explored how that status correlated with cognitive, functional and behavioural variables and caregiver overburden. The characteristics of the diet and the degree of adherence to the Mediterranean diet were also analysed. METHODS: This was a cross-sectional study that was representative of the general population and it was carried out in the Unit of Cognitive Disorders, Lleida, Spain. The participants were 111 subjects with AD who were aged 65 and over and still living at home. The subjects' nutritional status was assessed using the Mini Nutritional Assessment (MNA) and Controlling Nutritional Status system. The monthly food intake was estimated using the short Food Frequency Questionnaire and adherence to the Mediterranean diet was evaluated using the Mediterranean Diet Score. The Mini Mental State Examination (MMSE), Global Deterioration Scale, Neuropsychiatric Inventory (NPI) and Zarit Burden Interview (ZBI) were also used. RESULTS: We found that 68% of the subjects presented with a risk of malnutrition and 19% were malnourished according to the MNA scale. Patients ate a higher quantity of meat and dairy products than recommended and fewer products from the remaining healthier food groups. Of the 111 subjects, 73% showed low adherence to the Mediterranean diet and 27% showed moderate adherence. There was a partial correlation between nutritional status and the MMSE when the data were adjusted for age and sex (r = 0, 318; p = 0.001) and inverse correlations were found for functional status (r =  - 0.283; p = 0.004) and the NPI (r =  - 0.409; p = 0.000) and ZBI scales (r =  - 0.433; p = 0.000) when they were adjusted using the same variables. The ZBI scale (OR 1.08, 95% CI [1.01-1.15]) showed an increase in the risk of malnutrition in the multivariate analysis. DISCUSSION: Alterations in nutritional status were more common during the advanced stages of AD and were also associated with behavioural changes and caregiver overburden. Low adherence to traditional healthy diets in Mediterranean countries and food intake profiles should be considered when managing patients with AD. Other countries can use the results to examine diets in people with AD that are high in meat and dairy and low in healthy food groups like fruit and vegetables.

Utilidad de los nuevos criterios diagnósticos y la introducción de los biomarcadores en el continuum de la enfermedad de Alzheimer / Usefullness of new diagnosis criteria and introduction of biomarkers in Alzheimer’s disease continuum

Objetivos: los nuevos criterios diagnósticos de enfermedad de Alzheimer (EA) y deterioro cognitivo leve (DCL) apoyan la utilización de los biomarcadores. Valoramos la utilidad de añadir los biomarcadores en la práctica clínica habitual para confirmar y/o modificar el grado de certeza en el diagnóstico de EA y DCL. Pacientes y métodos: presentamos 40 pacientes en los que de forma consecutiva se realizó la determinación de biomarcadores en líquido cefalorraquídeo (LCR) (amilode, tau y p-tau) y evaluación neuropsicológica según los criterios establecidos en nuestra unidad. Resultados: presentamos las características demográficas de los pacientes. En el 52 % de los pacientes los biomarcadores permitieron modificar el grado de certeza del diagnóstico. La mayor aportación es poder reclasificar a los pacientes con DCL en pacientes con DCL y alto riesgo de EA (7), riesgo intermedio (6) o riesgo bajo (12). En dos casos de inicio rápidamente progresivo, los biomarcadores fueron compatibles con EA. Además, su determinación basal ayuda a predecir el riesgo de progresión a EA tras 2 años de seguimiento. Conclusiones: la utilización de los biomarcadores en la práctica clínica habitual ayuda a modificar el grado de certeza del diagnóstico clínico y, por tanto, el pronóstico de los pacientes, especialmente en fase prodrómica y en presentaciones atípicas (AU)

Background: The new diagnostic criteria for Alzheimer's disease (AD) and mild cognitive impairment (MCI) supports the use of biomarkers. We appreciate the value of adding biomarkers to routine clinical practice to confirm and/or modify the degree of certainty in the diagnosis of AD and MCI. Methods: We present 40 patients consecutively determining CSF biomarkers (amyloid, tau and p-tau) and neuropsychological evaluation was performed according to the criteria set out in our unit. Results: We present the demographic characteristics of the patients. In 52% of patients allowed biomarkers modify the degree of certainty of the diagnosis. The greatest contribution is to reclassify patients with MCI in MCI patients at high risk of AD (7), intermediate risk (7) or low risk of AD (12). In both cases of rapidly progressive onset biomarkers were consistent with AD. Besides, basal CSF biomarkers are useful to predict progression to AD after two years follow-up. Conclusion: The use of biomarkers in clinical practice helps to modify the degree of certainty of the clinical diagnosis, and therefore the prognosis of patients, especially in prodromal phase and atypical presentations (AU)