Agreement of cerebrospinal fluid biomarkers and amyloid-PET in a multicenter study.

Core Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers have shown incomplete agreement with amyloid-positron emission tomography (PET). Our goal was to analyze the agreement between AD CSF biomarkers and amyloid-PET in a multicenter study. Retrospective multicenter study (5 centers). Participants who underwent both CSF biomarkers and amyloid-PET scan within 18 months were included. Clinical diagnoses were made according to latest diagnostic criteria by the attending clinicians. CSF Amyloid Beta1-42 (Aß1-42, A), phosphorliated tau 181 (pTau181, T) and total tau (tTau, N) biomarkers were considered normal (-) or abnormal ( +) according to cutoffs of each center. Amyloid-PET was visually classified as positive/negative. Agreement between CSF biomarkers and amyloid-PET was analyzed by overall percent agreement (OPA). 236 participants were included (mean age 67.9 years (SD 9.1), MMSE score 24.5 (SD 4.1)). Diagnoses were mild cognitive impairment or dementia due to AD (49%), Lewy body dementia (22%), frontotemporal dementia (10%) and others (19%). Mean time between tests was 5.1 months (SD 4.1). OPA between single CSF biomarkers and amyloid-PET was 74% for Aß1-42, 75% for pTau181, 73% for tTau. The use of biomarker ratios improved OPA: 87% for Aß1-42/Aß1-40 (n = 155), 88% for pTau181/Aß1-42 (n = 94) and 82% for tTau/Aß1-42 (n = 160). A + T + N + cases showed the highest agreement between CSF biomarkers and amyloid-PET (96%), followed by A-T-N- cases (89%). Aß1-42/Aß1-40 was a better marker of cerebral amyloid deposition, as identified by amyloid tracers, than Aß1-42 alone. Combined biomarkers in CSF predicted amyloid-PET result better than single biomarkers.

Clinical impact of microbleeds in patients with Alzheimer's disease.

INTRODUCTION: Cerebral microbleeds (CMBs) are more frequent in patients with Alzheimer's disease (AD) than in the general population. However, their clinical significance remains poorly understood. We carried out a multimodal approach to evaluate the impact of CMBs at a clinical, neuropsychological, and survival level, as well as on core AD biomarkers in the cerebrospinal fluid (CSF) in AD patients. METHODS: We prospectively recruited 98 patients with mild-moderate AD. At baseline, they underwent brain MRI, and AD CSF biomarkers and APOE genotypes were analysed. An extensive neuropsychological battery was performed at baseline and after 1 year of follow-up. We analysed the stroke incidence and mortality with survival analyses. RESULTS: Forty-eight (48.5%) patients had at least one CMBs. Eight (8.2%) patients had strictly nonlobar CMBs, 39 (40.2%) had any lobar CMB locations. The incidence of stroke was higher in AD patients with lobar CMBs than in those without CMBs (p < 0.05). Mortality did not differ among groups (p > 0.05). At the cognitive level, CMBs patients deteriorated more rapidly at 12 months according to MMSE scores, with no differences observed at 24 months. We did not observe differences in the other tests, except for an increase in caregiver burden in the CMBs group. The presence of cerebral amyloidosis and APOE ε4 were associated with a greater presence of CMBs. CONCLUSION: CMBs are associated with an increased risk of ischemic stroke in AD patients without differences in mortality. Patients with CMBs did not seem to have different consequences associated with cognitive decline except for an increase in caregiver overload.

Understanding the Episodic Memory and Executive Functioning Axis Impairment in MCI Patients: A Multicenter Study in Comparison with CSF Biomarkers.

BACKGROUND: This study aimed to explore the association between a verbal learning task that evaluates the potential mutual dependency between memory and executive functions (i.e., the Test of Memory Strategies, TMS) and cerebrospinal fluid (CSF) Alzheimer's Disease (AD) biomarkers. METHODS: A sample of 47 mild cognitive impairment (MCI) participants from Poland and Spain were classified according to the Erlangen Score Diagnostic Algorithm (ESA) into CSF- (n = 16) and CSF+ (n = 31) groups. Correlation analyses between TMS word-list conditions and CSF biomarkers were conducted. Additionally, an analysis of covariance was performed to define the effect on ESA classification in the sample, using as a covariable the country of origin of the participants. RESULTS: Significant associations between the TMS-3 condition and Aß42, t-tau, and p-tau were observed for the whole sample. In addition, the CSF- participants obtained higher cognitive performance in TMS-3 compared to the CSF+ group. This outcome persisted if the groups were based on Aß42 scores, but not t-tau or p-tau values. CONCLUSIONS: These findings could indicate that poor performance on verbal learning tests may be affected by executive dysfunctions. Therefore, future intervention plans focused on training executive functions would be of interest to improve the ability of MCI patients to encode and organize information.

Depression and Apathy After Transient Ischemic Attack or Minor Stroke: Prevalence, Evolution and Predictors.

Few previous studies have focused on affective impairment after transient ischemic attack (TIA) and/or minor stroke. The aim was to establish the prevalence, evolution and predictors of post-stroke depression (PSD) and post-stroke apathy (PSA) over a 12-month follow-up period. We prospectively included TIA and minor stroke patients (NIHSS ≤4) who had undergone magnetic resonance imaging <7 days. PSD was diagnosed according to DSM-5 criteria and PSA was defined based on an Apathy Evaluation Scale (AES-C) score of ≥37. Clinical and neuroimaging variables (presence and patterns of lesion, cerebral bleeds and white matter disease) were analysed in order to find potential predictors for PSD and PSA. Follow-up was performed at 10 days and after 2, 6, 9 and 12 months. 82 patients were included (mean 66.4 [standard deviation11.0] years) of whom 70 completed the follow-up. At 10 days, 36 (43.9%) and 28 (34.1%) patients respectively were diagnosed with PSD and PSA. At 12 months, 25 of 70 (35.7%) patients still had PSA, but only 6 of 70 (8.6%) had PSD. Beck Depression Inventory-II score, mini mental state examination (MMSE) and a previous history of depression or anxiety were predictors for PSD. While MMSE score, The Montgomery Asberg Depression Rating Scale and having previously suffered a stroke were also risk factors for PSA. Acute basal ganglia lesion and periventricular leukoaraiosis were associated with PSA while deep leukorariosis with PSD. Despite the presence of few or only transient symptoms, PSD and PSA frequent appear early after TIA and minor stroke. Unlike PSD, apathy tends to persist during follow-up.

[The role of the neuropsychologist in neurology services: a descriptive study of the users of the specialised neurological assessment unit of the Hospital Complex of Navarra during its first year in service]. / Papel del neuropsicologo en los servicios de neurologia: estudio descriptivo de los usuarios de la consulta especializada de evaluacion neuropsicologica del Complejo Hospitalario de Navarra en su primer año de funcionamiento.

INTRODUCTION. A large number of neurological diseases course with impairment of higher cognitive functions, their evaluation being important for diagnostic, prognostic and therapeutic purposes. The main purpose of neuropsychological assessment is to identify behavioral, emotional and cognitive consequences of brain dysfunction. The neuropsychologist's figure was included in Navarra's Hospital Neurology Service in February 2013 through a specialized practice in neuropsychological assessment. AIM. To describe the sociodemographic and clinical profile of all patients referred to the same from March 2013 to March 2014. PATIENTS AND METHODS. A total of 511 people have been treated in this practice. RESULTS. 73.2% are more than 55 years old and the most frequent reason of referral is to characterize the neuropsychological profile to detect and discriminate mild cognitive impairment and dementia, as well as the type of dementia. In younger adults (< 55 years old) the most prevalent cognitive deficit is memory impairment. CONCLUSIONS. The expert neuropsychologist performs thorough neuropsychological evaluations from an interpretative approach. The results of this study suggest the importance of this figures role in neurology services and point out future aims.

TITLE: Papel del neuropsicologo en los servicios de neurologia: estudio descriptivo de los usuarios de la consulta especializada de evaluacion neuropsicologica del Complejo Hospitalario de Navarra en su primer año de funcionamiento.Introduccion. Un gran numero de patologias neurologicas cursa con afectacion de las funciones cognitivas superiores, y su valoracion es importante con fines diagnosticos, pronosticos y terapeuticos. El principal objetivo de la evaluacion neuropsicologica es identificar las consecuencias conductuales, emocionales y cognitivas de la disfuncion cerebral. La figura del neuropsicologo se incluyo en el servicio de neurologia del Complejo Hospitalario de Navarra en febrero de 2013 a traves de una consulta especializada de evaluacion neuropsicologica. Objetivo. Describir el perfil sociodemografico y clinico del total de pacientes derivados a consulta de marzo de 2013 a mar­zo de 2014. Pacientes y metodos. Se ha atendido a un total de 511 personas en esta consulta. Resultados. El 73,2% tiene mas de 55 años y el motivo de derivacion mas frecuente es la caracterizacion del perfil neuropsicologico para detectar y discriminar deterioro cognitivo leve y demencia, asi como el tipo de demencia. En los adultos jovenes (< 55 años), el deficit cognitivo mas prevalente es la afectacion de la memoria. Conclusiones. El neuropsicologo experto realiza evaluaciones neuropsicologicas exhaustivas desde un enfoque interpretativo. Los resultados de este estudio apuntan la relevancia de su funcion en los servicios de neurologia y descubre objetivos futuros.