LAM Test: A New Cognitive Marker for Early Detection in Preclinical Alzheimer's Disease.

Background: With the arrival of disease-modifying treatments, it is mandatory to find new cognitive markers that are sensitive to Alzheimer's disease (AD) pathology in preclinical stages. Objective: To determine the utility of a newly developed Learning and Associative Memory face test: LAM test. This study examined the relationship between AD cerebrospinal fluid (CSF) biomarkers and performance on LAM test, and assessed its potential clinical applicability to detect subtle changes in cognitively healthy subjects at risk for AD. Methods: We studied eighty cognitively healthy volunteers from the Valdecilla cohort. 61% were women and the mean age was 67.34 years (±6.416). All participants underwent a lumbar puncture for determination of CSF biomarkers and an extensive neuropsychological assessment, including performance on learning and associative memory indices of the LAM-test after 30 min and after 1 week, and two classic word lists to assess verbal episodic memory: the Rey Auditory Verbal Learning Test (RAVLT) and the Free and Cued Selective Reminding Test (FCSRT). We analyzed cognitive performance according to amyloid status (A+ versus A-) and to ATN model (A-T-N-; A+T-N-; A+T+N-/A+T+N+). Results: Performance on the LAM-test was significantly correlated with CSF Aß ratio. A+ participants performed worse on both learning (mean difference = 2.19, p = 0.002) and memory LAM measures than A- (mean difference = 2.19, p = 0.004). A decline in performance was observed along the Alzheimer's continuum, with significant differences between ATN groups. Conclusions: Our findings suggest that LAM test could be a useful tool for the early detection of subjects within the AD continuum, outperforming classical memory tests.

Plasma Phosphorylated Tau 231 Increases at One-Year Intervals in Cognitively Unimpaired Subjects.

Background: Plasma biomarkers of Alzheimer's disease (AD) constitute a non-invasive tool for diagnosing and classifying subjects. They change even in preclinical stages, but it is necessary to understand their properties so they can be helpful in a clinical context. Objective: With this work we want to study the evolution of p-tau231 plasma levels in the preclinical stages of AD and its relationship with both cognitive and imaging parameters. Methods: We evaluated plasma phosphorylated (p)-tau231 levels in 146 cognitively unimpaired subjects in sequential visits. We performed a Linear Mixed-effects Model to analyze their rate of change. We also correlated their baseline levels with cognitive tests and structural and functional image values. ATN status was defined based on cerebrospinal fluid biomarkers. Results: Plasma p-tau231 showed a significant rate of change over time. It correlated negatively with memory tests only in amyloid-positive subjects. No significant correlations were found with any imaging measures. Conclusions: Increases in plasma p-tau231 can be detected at one-year intervals in cognitively healthy subjects. It could constitute a sensitive marker for detecting early signs of neuronal network impairment by amyloid.

Influence of Physiological Variables and Comorbidities on Plasma Aß40, Aß42, and p-tau181 Levels in Cognitively Unimpaired Individuals.

Plasma biomarkers for Alzheimer's disease (AD) are a promising tool that may help in early diagnosis. However, their levels may be influenced by physiological parameters and comorbidities that should be considered before they can be used at the population level. For this purpose, we assessed the influences of different comorbidities on AD plasma markers in 208 cognitively unimpaired subjects. We analyzed both plasma and cerebrospinal fluid levels of Aß40, Aß42, and p-tau181 using the fully automated Lumipulse platform. The relationships between the different plasma markers and physiological variables were studied using linear regression models. The mean differences in plasma markers according to comorbidity groups were also studied. The glomerular filtration rate showed an influence on plasma Aß40 and Aß42 levels but not on the Aß42/Aß40 ratio. The amyloid ratio was significantly lower in diabetic and hypertensive subjects, and the mean p-tau181 levels were higher in hypertensive subjects. The glomerular filtration rate may have an inverse relationship on plasma Aß40 and Aß42 levels but not on the amyloid ratio, suggesting that the latter is a more stable marker to use in the general population. Cardiovascular risk factors might have a long-term effect on the amyloid ratio and plasma levels of p-tau181.

Age-related hearing loss is not linked to cerebrospinal fluid levels of ß-amyloid or p-tau181.

INTRODUCTION: As Hearing loss and dementia affect people with the same profile, several epidemiological studies have evaluated their relationship. However, the link between age-related hearing loss and Alzheimer's disease is still unclear. METHODS: We selected subjects with no history of exposure to loud noises, blasts, head trauma with hearing loss, or sudden sensorineural hearing loss from a cohort intended to study preclinical phases of Alzheimer's disease. Participants are volunteers over 55 years without cognitive impairment. We correlated the results of an objective auditory evaluation with brain amyloid and p-tau181 levels and with the outcomes of a comprehensive neuropsychological assessment. RESULTS: Fifty-five subjects at different stages of the Alzheimer's disease continuum were evaluated. There were no statistically significant correlations between amyloid-ß and p-tau levels and any of the objective auditory measures. A weak but significant correlation was found between amyloid-ß values and the Hearing Handicap Inventory for the Elderly. The neuropsychological domains more correlated to hearing loss were executive function and processing speed. DISCUSSION: Age-related hearing loss is not linked to any pathological markers of Alzheimer's disease nor to neuropsychological domains typically affected in this disease. The Hearing Handicap Inventory for the Elderly has an important component of subjectivity and further studies are needed to explore its relationship with amyloid-ß levels.

Accuracy of plasma Aß40, Aß42, and p-tau181 to detect CSF Alzheimer's pathological changes in cognitively unimpaired subjects using the Lumipulse automated platform.

BACKGROUND: The arrival of new disease-modifying treatments for Alzheimer's disease (AD) requires the identification of subjects at risk in a simple, inexpensive, and non-invasive way. With tools allowing an adequate screening, it would be possible to optimize the use of these treatments. Plasma markers of AD are very promising, but it is necessary to prove that alterations in their levels are related to alterations in gold standard markers such as cerebrospinal fluid or PET imaging. With this research, we want to evaluate the performance of plasma Aß40, Aß42, and p-tau181 to detect the pathological changes in CSF using the automated Lumipulse platform. METHODS: Both plasma and CSF Aß40, Aß42, and p-tau181 have been evaluated in a group of 208 cognitively unimpaired subjects with a 30.3% of ApoE4 carriers. We have correlated plasma and CSF values of each biomarker. Then, we have also assessed the differences in plasma marker values according to amyloid status (A - / +), AD status (considering AD + subjects to those A + plus Tau +), and ATN group defined by CSF. Finally, ROC curves have been performed, and the area under the curve has been measured using amyloid status and AD status as an outcome and different combinations of plasma markers as predictors. RESULTS: Aß42, amyloid ratio, p-tau181, and p-tau181/Aß42 ratio correlated significantly between plasma and CSF. For these markers, the levels were significantly different in the A + / - , AD + / - , and ATN groups. Amyloid ratio predicts amyloid and AD pathology in CSF with an AUC of 0.89. CONCLUSIONS: Plasma biomarkers of AD using the automated Lumipulse platform show good diagnostic performance in detecting Alzheimer's pathology in cognitively unimpaired subjects.

Alteraciones cognitivas asociadas al patrón de bebedor de fin de semana en estudiantes universitarios: resultados preliminares / Cognitive impairment associated to binge drinking in university students: A preliminary analysis

Objetivo: evaluar el efecto del consumo de alcohol con patrón de bebedor de fin de semana (BD, del inglés binge drinkers) sobre la memoria y la función ejecutiva en estudiantes universitarios. Material y métodos: se realizó un estudio transversal en universitarios de las Escuelas Universitarias Gimbernat-Cantabria. Se recogieron datos sociodemográficos y hábitos de vida de 102 alumnos (media de edad 19,6 ± 0,25 años; 69,6 % mujeres). Se evaluó la memoria y la función ejecutiva utilizando una batería de test cognitivos validados y normalizados para la población española. Los participantes fueron clasificados en bebedores BD (consumidores de seis o más unidades de bebidas alcohólicas en 2 h) y no BD mediante el cuestionario de hábitos de vida. Se empleó la prueba de la t de Student para evaluar la asociación entre test cognitivos y patrón de consumo. Se realizaron análisis multivariantes mediante regresión lineal para ajustar por covariables sociodemográficas. Resultados: todos los estudiantes refirieron haber consumido alcohol en alguna ocasión. La media de edad de inicio del consumo fue de 15 ± 0,12 años. El 49 % de los estudiantes presentaba un patrón BD. Los bebedores BD difirieron significativamente en los resultados del Trail Making Test B (TMTB), que evalúa la función ejecutiva (42,7 ± 2,0 BD frente a 36,3 ± 1,2 no BD promedio segundos; p = 0,007). Ajustando por edad, sexo y expediente académico, la asociación entre TMTB y patrón BD fue también estadísticamente significativa (p = 0,020). La edad de inicio del consumo de alcohol se correlacionó de forma inversa con los resultados en el TMTB (r2 = -0,22; p = 0,027). Conclusión: el patrón de consumo de alcohol BD en estudiantes universitarios se asoció a un menor rendimiento en el test de función ejecutiva TMTB. Los inicios tempranos en el consumo de alcohol se correlacionaron con peores puntuaciones en TMTB, lo que sugiere un efecto acumulativo (AU)

Objective: To evaluate the effects of the alcohol consumption on memory and on executive function in university students who are consistent with the pattern of binge drinkers (BD). Materials and methods: A transversal study was conducted on university students at the University School of Gimbernat-Cantabria. Sociodemographic data and life habits were collected from 102 students (average age 19.6 ± 0.25 years; 69.6% women). Memory and executive functions were evaluated through a range of validated cognitive tests. Participants were classified as BD (consumers of six or more units of alcoholic drinks in 2 hours) and non BD. Besides, it was also studied the association between cognitive tests and the pattern of consumption through the student’s t-test. A multivaried analysis was carried out to adjust the sociodemographic cofactors. Results: All students admitted having consumed alcohol on occasion. The average age of the onset of consumption was 15 ± 0.12. 49% of the students had a pattern of BD. These binge drinkers differed significantly in their results of the Trail Making Test B (TMTB), an executive function test (42,7 ± 2,0 vs. 36,3 ± 1,2 second average; p = 0,007). Adjusting by age, sex and academic records, the association between TMTB and the pattern of BD was significant (p = 0,020). The age of onset of alcohol use was correlated inversely with the results in the TMTB (r2 = -0.22, p = 0.027). Discussion/Con - clusion: BD alcohol consumption pattern was associated in college students with a lower performance during the executive function test TMTB. Earlier alcohol consumption was associated to worse performances in TMTB, suggesting an accumulative effect (AU)