La apatía en la demencia frontotemporal y la enfermedad de Alzheimer: estudio clínico y de neuroimagen funcional

La apatía es uno de los síndromes neuropsiquiátricos más frecuentes e invalidantes de las demencias, y puede presentarse en cualquier estadio de la enfermedad. La presencia de la apatía en enfermedades neurodegenerativas se ha relacionado con una mayor morbilidad y un peor pronóstico, y con una mayor carga de estrés para el cuidador. Recientemente, se han propuesto unos criterios clínicos para el diagnóstico de apatía en la enfermedad de Alzheimer (EA) y otros trastornos neuropsiquiátricos. De acuerdo con la clasificación original de Marin, estos criterios se organizan en torno a tres dominios y resaltan la necesidad de una evaluación multidimensional de la apatía. Actualmente, la literatura existente acepta que se pueden distinguir tres subtipos o dimensiones de la apatía, asociados a disfunción de diferentes circuitos neurales: apatía cognitiva, apatía emocional y apatía por disfunción en la autoactivación. En castellano, tan sólo existen dos escalas validadas en demencias que evalúen la apatía desde un punto de vista multidimensional: la Lillés Apathy Rating Scale (LARS) y la Apathy Scale for Institutionalized Patients with Dementia Nursing Home version (APADEM-NH). La escala APADEM-NH está diseñada para evaluar la apatía en pacientes institucionalizados con EA mediante la entrevista a un cuidador profesional, por lo que no es válida para pacientes ambulatorios. La LARS consta de nueve dominios o subescalas (“Productividad diaria”, “Aficiones”, “Tomar la iniciativa”, “Búsqueda de novedades”, “Motivación”, “Respuesta emocional”, “Preocupación”, “Vida social” y “Autoconsciencia”), que pueden combinarse para calcular cuatro dimensiones de la apatía: “Curiosidad intelectual”, “Emoción”, “Iniciativa de acción” y “Autoconsciencia”. La versión en castellano de la LARS ha sido recientemente validada por nuestro grupo en una cohorte de pacientes con demencia, mostrando excelentes propiedades psicométricas..

Lewy Body Dementias: A Coin with Two Sides?

Lewy body dementias (LBDs) consist of dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD), which are clinically similar syndromes that share neuropathological findings with widespread cortical Lewy body deposition, often with a variable degree of concomitant Alzheimer pathology. The objective of this article is to provide an overview of the neuropathological and clinical features, current diagnostic criteria, biomarkers, and management of LBD. Literature research was performed using the PubMed database, and the most pertinent articles were read and are discussed in this paper. The diagnostic criteria for DLB have recently been updated, with the addition of indicative and supportive biomarker information. The time interval of dementia onset relative to parkinsonism remains the major distinction between DLB and PDD, underpinning controversy about whether they are the same illness in a different spectrum of the disease or two separate neurodegenerative disorders. The treatment for LBD is only symptomatic, but the expected progression and prognosis differ between the two entities. Diagnosis in prodromal stages should be of the utmost importance, because implementing early treatment might change the course of the illness if disease-modifying therapies are developed in the future. Thus, the identification of novel biomarkers constitutes an area of active research, with a special focus on α-synuclein markers

Validation of the Spanish Version of the LASSI-L for Diagnosing Mild Cognitive Impairment and Alzheimer's Disease

The Loewenstein-Acevedo Scale for Semantic Interference and Learning (LASSI-L) is a novel cognitive test that measures recovery from proactive semantic interference, which may be an early cognitive marker of Alzheimer's disease (AD). To generate normative data for a Spaniard population and to validate the LASSI-L for the diagnosis of amnestic mild cognitive impairment (aMCI) and mild AD. We performed a cross-sectional study in which 97 healthy participants, 34 with aMCI, and 33 with mild AD were studied with LASSI-L and a comprehensive neuropsychological protocol. The overlapping strategy analysis was used to maximize the sample size and to provide age- and education-adjusted normative data using a logistic regression analysis. Internal consistency was 0.932. Convergent validity with the Free and Cued Selective Reminding Test was moderate. LASSI-L raw scores were correlated with age and years of education, but not gender. The area under the curve for discriminating between healthy controls and aMCI was 0.909, and between healthy controls and mild AD was 0.986. LASSI-L sub-scores representing maximum storage capacity, recovery from proactive interference, and delayed recall yielded the highest diagnostic accuracy. The LASSI-L is a reliable and valid test for the diagnosis of aMCI and mild AD. The age and education influences on the performance of the test and normative data are provided. LASSI-L merits further studies to evaluate its ability to detect preclinical AD and predict progression to aMCI and early dementia

Accuracy of plasma Abeta40, Abeta42, 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 identifca tion 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 neces sary to prove that alterations in their levels are related to alterations in gold standard markers such as cerebrospinal fuid or PET imaging. With this research, we want to evaluate the performance of plasma Aβ40, Aβ42, and p-tau181 to detect the pathological changes in CSF using the automated Lumipulse platform. Methods Both plasma and CSF Aβ40, Aβ42, and p-tau181 have been evaluated in a group of 208 cognitively unim paired subjects with a 30.3% of ApoE4 carriers. We have correlated plasma and CSF values of each biomarker. Then, we have also assessed the diferences in plasma marker values according to amyloid status (A−/+), AD status (consider ing AD+subjects to those A+plus Tau+), and ATN group defned 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 diferent combinations of plasma markers as predictors. Results Aβ42, amyloid ratio, p-tau181, and p-tau181/Aβ42 ratio correlated signifcantly between plasma and CSF. For these markers, the levels were signifcantly diferent in the A+/−, AD+/−, and ATN groups. Amyloid ratio pre dicts 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