Correlation Between Amyloid PET Imaging and Discordant Cerebrospinal Fluid Biomarkers Results in Patients with Suspected Alzheimer's Disease.

BACKGROUND: Although the concordance between cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarkers and amyloid-PET findings is well known, there are no data regarding the concordance of amyloid-PET with inconclusive CSF values of amyloid-ß (Aß)1 - 42 and p-tau for the diagnosis of AD. OBJECTIVE: To investigate the relationship between the amyloid-PET results with discordant AD biomarkers values in CSF (Aß1 - 42+/p-tau-or Aß1 - 42-/p-tau+). METHODS: An observational retrospective study, including 62 patients with mild cognitive impairment (32/62) or dementia (30/62), suspicious of AD who had undergone a lumbar puncture to determine CSF AD biomarkers, and presented discordant values in CSF between Aß1 - 42 and p-tau (Aß1 - 42+/p-tau-or Aß1 - 42-/p-tau+). All of them, underwent an amyloid-PET with 18F-Florbetaben. An extensive neuropsychological testing as part of their diagnostic process (MMSE and TMA-93), was performed, and it was also obtained the Global Deterioration Scale. RESULTS: Comparing the discordant CSF results of each patient with the cerebral amyloid-PET results, we found that in the group with Aß1 - 42+ and p-tau-CSF values, the amyloid-PET was positive in 51.2% and negative in 48.8% of patients, while in the group with Aß1 - 42-and p-Tau+ CSF values, the amyloid-PET was positive in 52.6% of patients and negative in 47.4% of them. No significant association was found (p = 0.951) between the results of amyloid-PET and the two divergent groups in CSF. CONCLUSIONS: No significant relationship was observed between the results of discordant AD biomarkers in CSF and the result of amyloid-PET. No trend in amyloid-PET results was observed in relation to CSF biomarker values.

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.

TMA-93 Validation by Alzheimer's Disease Biomarkers: A Comparison with the Free and Cued Selective Reminding Test on a Biobank Sample.

BACKGROUND: The Memory Associative Test TMA-93 examines visual relational binding, characteristically affected in early-AD stages. OBJECTIVE: We aim to validate the TMA-93 by biomarkers determination and compare its diagnostic characteristics with the Free and Cued Selective Reminding Test (FCSRT). METHODS: Retrospective analysis of a Biobank database. Patients' records initially consulted for memory complaints, scored MMSE≥22, had TMA-93 and FCSRT tested, and AD biomarker determination (Amyloid-PET or CSF), either positive or negative, were selected. As cutoffs, we considered the 10-percentile for TMA-93 (P10/TMA-93), and "total free recall" (TFR) 21/22, total recall (TR) 43/44, and Cued Index < 0.77 for FCSRT from previous Spanish validation and normative studies. Diagnostic utilities were calculated using ROC curves and compared by the DeLong method. We studied if one test improved the other test's prediction, following a forward stepwise logistic regression model. RESULTS: We selected 105 records: 64 "positive" and 41 "negative" biomarkers. TMA-93 total score diagnostic utility (AUC = 0.72; 95%CI:0.62-0.82) was higher than those of the FCSRT: TFR (AUC = 0.70; 95%CI: 0.60-0.80), TR (AUC = 0.63; 95%CI:0.53-0.74), and Cued Index (AUC = 0.62; 95%CI:0.52-0.73). The P10/TMA-93 cutoff showed 86%sensitivity, similar to that of the most sensitive FCSRT cutoff (TFR21/22, 89%) and 29%specificity, lower than that of the most specific FCSRT cutoff (Cued Index < 0.77, 57%). 32.8%of the positive-biomarker group scored above CI/0.77 but below p10TMA-93. The addition of TMA-93 total score to FCSRT variables improved significantly the biomarkers results' prediction. CONCLUSION: TMA-93 demonstrated "reasonable" diagnostic utility, similar to FCSRT, for discriminating AD biomarker groups. TMA-93 total score improved the AD biomarker result prediction when added to FCSRT variables.

[Hemicrania continua and paroxysmal hemicrania: clinical and therapeutic characteristics in a series of 23 patients]. / Hemicránea continua y paroxística: características clínicas y terapéuticas en una serie de 23 pacientes.

INTRODUCTION: Hemicranias are an uncommon type of headache characterised by strictly unilateral pain, either as a continuous, although fluctuating, headache in hemicrania continua (HC) or in the form of recurring attacks in paroxysmal hemicrania (PH). In both types of headache, an absolute response to indomethacin is reported. AIMS. To analyse the fulfilment of current diagnostic criteria for HC and PH and the recent introduction of HC within the group of trigeminal-autonomic cephalgias. PATIENTS AND METHODS: The clinical and therapeutic characteristics of patients diagnosed with HC or PH were evaluated retrospectively. Demographic and symptomatological information as well as data regarding the analogical pain scale and response to indomethacin were included. RESULTS: A sample of 12 HC (four males and eight females) was evaluated from a total of 520 cases (2.3%). Mean age at onset: 47.1 ± 16.4 years. Baseline pain intensity: 3.3 ± 1,9. Exacerbations: 9.2 ± 1.1. Eight cases (66.7%) presented autonomic symptoms, four (33.3%) followed a time pattern, and two (16.7%) did not respond to indomethacin. We evaluated a sample of 11 PH (100% females) from 520 cases (2.1%). Mean age at onset: 37.0 ± 13.9 years. Pain intensity: 8.7 ± 2.7. Nine cases (81.8%) presented autonomic symptoms, three (27.3%) followed a time pattern and one (9.1%) did not respond to indomethacin. CONCLUSIONS: Hemicranias are not frequently diagnosed in day-to-day clinical practice. Their diagnosis requires the fulfilment of certain criteria that are sometimes not fully satisfied. We believe that the criteria need revising and we also support the recent inclusion of HC within the group of trigeminal-autonomic cephalgias.

TITLE: Hemicranea continua y paroxistica: caracteristicas clinicas y terapeuticas en una serie de 23 pacientes.Introduccion. Las hemicraneas son cefaleas raras caracterizadas por dolor estrictamente unilateral, bien como una cefalea continua, aunque fluctuante, en la hemicranea continua (HC), o en forma de ataques recurrentes en la hemicranea paroxistica (HP). En ambos tipos de cefalea se describe una respuesta absoluta a la indometacina. Objetivo. Analizar el cumplimiento de los criterios diagnosticos actuales para HC y HP, y la reciente introduccion de la HC en el grupo de las cefaleas trigeminoautonomicas. Pacientes y metodos. Evaluamos retrospectivamente las caracteristicas clinicas y terapeuticas de pacientes diagnosticados de HC o HP. Incluimos informacion demografica, sintomatologia, escala analogica de dolor y respuesta a la indometacina. Resultados. Evaluamos una muestra de 12 pacientes con HC (cuatro hombres y ocho mujeres) de un total de 520 casos (2,3%). Edad media de inicio: 47,1 ± 16,4 años. Intensidad de dolor basal: 3,3 ± 1,9. Exacerbaciones: 9,2 ± 1,1. Ocho casos (66,7%) presentaban sintomas autonomicos, cuatro (33,3%) tenian patron horario y dos (16,7%) no respondieron a la indometacina. Evaluamos una muestra de 11 pacientes con HP (100% mujeres) de 520 casos (2,1%). Edad media de inicio: 37,0 ± 13,9 años. Intensidad de dolor: 8,7 ± 2,7. Nueve casos (81,8%) presentaban sintomas autonomicos, tres (27,3%) tenian patron horario y uno (9,1%) no respondio a la indometacina. Conclusiones. Las hemicraneas son diagnosticos infrecuentes en consultas de cefalea. Su diagnostico requiere el cumplimiento de unos criterios que a veces no se cumplen en su totalidad. Pensamos que se precisa una revision de los criterios y apoyamos que la HC se haya introducido recientemente en el grupo de las cefaleas trigeminoautonomicas.