Episodic and semantic autobiographical memory in temporal lobe epilepsy

Autobiographical memory (AM) is understood as the retrieval of personal experiences that occurred in specific time and space. To date, there is no consensus on the role of medial temporal lobe structures in AM. Therefore, we investigated AM in medial temporal lobe epilepsy (TLE) patients. Twenty TLE patients candidates for surgical treatment, 10 right (RTLE) and 10 left (LTLE), and 20 healthy controls were examined with a version of the Autobiographical Interview adapted to Spanish language. Episodic and semantic AM were analyzed during five life periods through two conditions: recall and specific probe. AM scores were compared with clinical and cognitive data. TLE patients showed lower performance in episodic AM than healthy controls, being significantly worst in RTLE group and after specific probe. In relation to semantic AM, LTLE retrieved higher amount of total semantic details compared to controls during recall, but not after specific probe. No significant differences were found between RTLE and LTLE, but a trend towards poorer performance in RTLE group was found. TLE patients obtained lower scores for adolescence period memories after specific probe. Our findings support the idea that the right hippocampus would play a more important role in episodic retrieval than the left, regardless of a temporal gradient.Fil: Múnera Martínez, Claudia Patricia. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Lomlomdjian, Ana Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Gori, María Belén. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Terpiluk, Veronica. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Medel, Nancy Ruth. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Solis, Patricia. Universidad Nacional Arturo Jauretche. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Kochen, Sara Silvia. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Universidad Nacional Arturo Jauretche. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; Argentin

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

A study of word finding difficulties in Spanish speakers with temporal lobe epilepsy

It is well established that naming deficits can be found in temporal lobe epilepsy (TLE). The aim of this study was to determine in Spanish speakers with pharmacoresistant TLE the characteristics of subjective naming difficulties and to examine performance in a definition task and a picture task in left TLE and right TLE. We observed that almost one-third of patients report frequent and severe word finding problems during spontaneous speech. In naming tests, our patients exhibited delayed times for finding words. Even if the target word was identified and semantically activated, there was difficulty with lexical access, which improved when a phonetic cue was given. Left TLE patients derived a lower benefit from phonetic cues in accessing words, even when the word is known and recognized semantically. These findings were not related to any demographic or clinical characteristics analyzed. The fact that the only weakly lateralized variable has been a lexical access facilitation measurement could support a lexical access hypothesis for naming deficits in TLE.Fil: Lomlomdjian, Ana Carolina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Solis, P.. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Medel, Nancy Ruth. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Kochen, Sara Silvia. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentin

Memory for emotional material in temporal lobe epilepsy

Several studies suggest that highly emotional information could facilitate long-term memory encoding and consolidation processes via an amygdala-hippocampal network. Our aim was to assess emotional perception and episodic memory for emotionally arousing material in patients with temporal lobe epilepsy (TLE) who are candidates for surgical treatment. We did this by using an audiovisual paradigm. Forty-six patients with medically resistant TLE (26 with left TLE and 20 with right TLE) and 19 healthy controls were assessed with a standard narrative test of emotional memory. The experimental task consisted of sequential picture slides with an accompanying narrative depicting a story that has an emotional central section. Subjects were asked to rate their emotional arousal reaction to each stimulus after the story was shown, while emotional memory (EM) was assessed a week later with a multiple choice questionnaire and a visual recognition task. Our results showed that ratings for emotional stimuli for the patients with TLE were significantly higher than for neutral stimuli (p = 0.000). It was also observed that patients with TLE recalled significantly less information from each slide compared with controls, with a trend to lower scores on the questionnaire task for the group with LTLE, as well as poorer performance on the visual recognition task for the group with RLTE. Emotional memory was preserved in patients with RTLE despite having generally poorer memory performance compared with controls, while it was found to be impaired in patients with LTLE.Fil: Múnera Martínez, Claudia Patricia. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Lomlomdjian, Ana Carolina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Terpiluk, Verónica. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Medel, Nancy Ruth. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Solis, Patricia. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Kochen, Sara Silvia. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; Argentin

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

New insights into the genetic etiology of Alzheimer’s disease and related dementias

Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele