Basic Science and Pathogenesis.

Background: Autosomal dominant progranulin (GRN) mutations are a common genetic cause of frontotemporal lobar degeneration. Though clinical trials for GRN-related therapies are underway, there is an unmet need for biomarkers that can predict symptom onset and track disease progression. We previously showed that presymptomatic GRN carriers exhibit thalamocortical hyperconnectivity that increases with age when they are presumably closer to symptom onset.

Basic Science and Pathogenesis.

Background: Alzheimer's (AD) and Parkinson's disease (PD) feature progressive neurodegeneration in a remarkably regionally selective manner. Post mortem studies have posited a role for cell autonomous mechanisms driving this, so we aimed to examine a live human induced pluripotent stem cell (iPSC) model to see whether it can replicate the phenomenon of selective neuronal vulnerability, so to better determine disease mechanisms and therapeutic targets.

Method: iPSC-derived neurons offer a rare opportunity to examine cell autonomous vulnerability in live human cells.

Basic Science and Pathogenesis.

Background: Despite being the most common cause of dementia worldwide, the mechanisms underlying the progression of Alzheimer's disease (AD) are not clear and effective treatments are still needed. Hence, further investigation regarding the pathogenesis of AD is required, which might allow for a better understanding of the disease, as well as for an early diagnosis of AD, thus improving the clinical management of AD patients. Here, to identify key proteins in AD pathogenesis, we performed two proteomics strategies, TMT (Tandem Mass Tags) 10-plex quantitative proteomics and LFQ (Label Free Quantification).

Basic Science and Pathogenesis.

Background: Alzheimer's disease (AD) is a complex disorder and multiple cellular and molecular mechanisms are involved in AD onset and progression. Recent evidences have suggested that metabolic alterations are an important pathological feature in disease progression in AD. Likewise, diabetes and obesity, two mayor metabolic illnesses, are risk factors for AD.

Basic Science and Pathogenesis.

Background: We recently developed a novel tau-PET summary measure THETA, capturing regional heterogeneity and identifying tau status, using ground truth visual assessments from a large single-center cross-sectional dataset and validated on independent cohorts [1, 2]. In this study, we aimed to evaluate the performance of THETA on longitudinal and histopathology data.

Method: We included longitudinal tau-PET ([F]flortaucipir) data from 696 Mayo Clinic Study of Aging (MCSA) and ADRC participants, with histopathology in n = 90.

Basic Science and Pathogenesis.

Background: Transcriptomic and pathological studies indicate that microglia play a key role in the progression of Alzheimer's disease (AD). Throughout the stages of the AD continuum, there may be varying microglia phenotypes, such as the disease-associated microglia (DAM). Microglia proteins have been detected in cerebrospinal-fluid (CSF), providing a quantifiable avenue for potential stage-detection.

Basic Science and Pathogenesis.

Background: Synaptic degeneration is a primary neuropathological factor associated with cognitive decline in Alzheimer's disease (AD). In 2021, we generated a synaptic Polygenic Risk Score (PRS) that comprised only 8 variants within 6 synaptic genes (APOE, PICALM, BIN1, PTK2B, DLG2 and MINK1) that predicted AD with 72% accuracy in two neuropathological cohorts. This supports the hypothesis that genetic variants that regulate an individual's vulnerability to AD-related synapse degeneration could be used to identify individuals at-risk for AD prior to the appearance of clinical symptoms.

Basic Science and Pathogenesis.

Background: Synapse degeneration is one of the earliest changes in Alzheimer's disease (AD) and is the major neuropathologic correlate of cognitive impairment. The aim of this study was to characterize microRNA (miRNA) dysregulation at AD synapses post-mortem brain tissue and explore the specificity for AD.

Method: We prepared synaptosomes (SYN) by serial ultracentrifugation of 10 AD (mean age = 77.

Basic Science and Pathogenesis.

Background: Clear sex differences exist in AD and PD. Several studies examined genetic regulations for AD phenotypes and gene expression data in a sex-specific manner, identifying some differences between males and females. In contrasts, although proteins are final effectors of most physiological pathways and important drug targets, sex-specific regulations for proteins remain vastly understudied.

Clustering patients with COVID-19 according to respiratory support requirements, and its impact on short- and long-term outcome (RECOVID study).

Introduction: The Spanish Society of Pulmonology and Thoracic Surgery created a registry for hospitalised patients with COVID-19 and the different types of respiratory support used (RECOVID). Objectives. To describe the profile of hospitalised patients with COVID-19, comorbidities, respiratory support treatments and setting.

Clinical Manifestations.

Background: Subjective Cognitive Decline (SCD) may represent the initial symptom of Alzheimer's disease (AD), but SCD may be absent and/or unrelated to actual cognitive decline. Objective Subtle Cognitive Decline (obj-SCD) can be identified through longitudinal standardized neuropsychological tests in individuals not yet meeting criteria for Mild Cognitive Impairment (MCI). We argue that the relationship between SCD and obj-SCD might help to inform clinical and research criteria in pre-MCI stages.

Clinical Manifestations.

Background: The importance of coincidence of cognitive complaints between participants without objective impairment and their informants in predicting progression remains unclear (Nosheny et al, 2022). Our objective was to determine whether agreement in dyadic reporting at baseline can predict survival time to progression to MCI or dementia.

Method: A sample of 145 participants from the CompAS Study was included in a survival analysis.

Clinical Manifestations.

Background: Changes in speech and language functions have shown to be early symptoms of AD pathology. Recent developments in automatic speech and language processing have opened avenues for objective assessments of these changes. The primary objective of this study is to explore whether speech and language markers extracted from cognitive testing conducted during an automated phone call differ according to underlying AD pathology as measured in cerebrospinal fluid (CSF) in preclinical or early stage individuals.

Clinical Manifestations.

Background: Practice effects are a well-known cognitive phenomenon that is reduced in patients with Alzheimer's disease (AD). We aimed to investigate whether cognitively unimpaired (CU) individuals within the Alzheimer's continuum (i.e.

Clinical Manifestations.

Background: Neuromodulatory subcortical systems (NSS) are affected from the early stages of Alzheimer's Disease (AD) by the accumulation of tau pathology. Increased tau burden within the subcortical nucleus that are in control of sleep and wake regulation may contribute to the breakdown of sleep-wake patterns in AD. A recent postmortem study showed that subcortical wake-promoting neurons were related to sleep phenotypes in AD and PSP, being that greater neuronal count in locus coeruleus (LC), tuberomammillary nucleus (TMN), and lateral hypothalamic area (LHA) associated with a decreased sleep drive (Oh et al.

Clinical Manifestations.

Background: In cognitively unimpaired (CU) older adults, the presence of a subjective cognitive decline (SCD) combined with evidence of abnormal b-amyloid (Ab) is proposed as stage 2 of Alzheimer's disease (AD) by the NIA-AA framework (Jack et al., 2018). However, the associations found between SCD and preclinical AD are inconsistent across studies, highlighting the importance of better understanding which specific SCD features are associated with either Ab or tau burden.

Clinical Manifestations.

Background: Alzheimer's disease and related dementias (ADRD) disproportionately affect Latinos compared to non-Latino whites. Leveraging the non-monolithic structure of Latin America, which represents a large variability in social determinants of health (SDoH) and high levels of genetic admixture, we aimed to determine contributors to ADRD disparities within Latinos, focusing on genetic ancestry and SDoH.

Method: Community-dwelling participants aged 65 and older (n = 4000) from Cuba, Dominican Republic, Mexico, and Peru completed the 10/66 protocol assessments, including sociodemographic and risk factors questionnaire, neurological exam, cognitive assessment, and blood draw.

Clinical Manifestations.

Background: In the present study we aimed to assess the cognition of post-COVID condition (PCC) participants regarding their sleep quality, and to analyse different possible moderators of this effect, such as quality of life (European Quality of Life-5 Dimensions, EQ-5D), fatigue (Chadler Fatigue Questionnaire, CFQ), cognitive reserve (Cognitive Reserve Questionnaire, CRC), and subjective cognitive complaints (Memory Failures of Everyday Questionnaire, MFE-30).

Method: We included 373 individuals with PCC and 126 healthy controls (HCs) from the NAUTILUS Project (NCT05307549 and NCT05307575) that were assessed with a comprehensive neuropsychological battery and different questionnaires.

Result: We included 373 individuals with PCC and 126 healthy controls (HCs) from the NAUTILUS Project (NCT05307549 and NCT05307575) that were assessed with a comprehensive neuropsychological battery and different questionnaires.

Clinical Manifestations.

Background: Objective Subtle Cognitive Decline (obj-SCD) can be identified through standardized neuropsychological tests and may precede the development of Mild Cognitive Impairment (MCI). Nevertheless, current clinical and research criteria lack a standardized protocol for identifying obj-SCD. This study introduces cutting-edge sensitive methods to characterize obj-SCD, defined through Alzheimer's disease (AD) biomarker-based longitudinal cognitive performance in episodic memory.

Omega 6 fatty acids: helpful, harmless or harmful?

Purpose Of Review: This paper reviews the most recent literature from January 2023 to August 2024 on the physiological effects of n-6 polyunsaturated fatty acids (PUFAs), with a focus on linoleic acid (LA).

Recent Findings: Contrary to previous concerns that high LA intake may increase inflammation, most recent evidence supports the benefits of LA for cardiometabolic health. Several large studies report that higher blood LA levels correlate with reduced risks of coronary heart disease, stroke, and type 2 diabetes.

Clinical Manifestations.

Background: The role of neuropsychiatric symptoms (NPS) as early markers of cognitive impairment progression along the cognitive impairment continuum needs further research. Our objective was to estimate to which extent NPS, measured with the Mild Behavioral Impairment Checklist (MBI-C), predict time-to-cognitive-worsening during follow-up in a sample of older adults recruited from primary care centers while controlling for other related variables (i.e.

Clinical Manifestations.

Background: Neuropsychological performance guides diagnostic and therapeutic decision-making on Alzheimer's disease (AD) and related disorders. Despite broad recognition that amyloid-beta (Aβ) impacts cognition during preclinical AD, the added value of Aβ-negative norms remains uncertain. Furthermore, normative modeling is constrained by limitations inherent to traditional methods.

Clinical Manifestations.

Background: This study focused on comparing clinical and neuropsychological aspects in individuals with subjective cognitive decline (SCD) versus healthy controls (HCs) in a memory clinic, aiming to identify factors linked to the progression towards mild cognitive impairment (MCI) or dementia.

Method: We retrospectively analysed data from 945 SCD patients and 68 HCs at Clínica Universidad de Navarra memory clinic between 2001 and 2017, with 450 followed up until January 2020, the study involved various assessments including medical interviews, lab tests, neuropsychological evaluations (during the first interview and follow-ups), and brain imaging. All the neuropsychological variables were adjusted for age, sex and education.

Absolute Dimensionality of Quantum Ensembles.

The dimension of a quantum state is traditionally seen as the number of superposed distinguishable states in a given basis. We propose an absolute, i.e.