Basic Science and Pathogenesis.

Background: Current evidence suggests that hippocampal subfields have partially different genetic architecture and may improve the sensitivity of the detection of Alzheimer's disease (AD). In this study, we investigated whether genetic predisposition to AD contributes to the accelerated rate of hippocampal volume atrophy across sex and AD stages and how this contribution is specifically driven by functional variants located in the APOE gene.

Methods: The study comprised 1,051 participants from ADNI cohort (75.

Basic Science and Pathogenesis.

Background: The hippocampus is highly vulnerable to amyloid-b (Aβ) and phosphorylated tau (p-tau), and shows synaptic loss in Alzheimer's disease (AD). Moreover, the loss of synapses correlates strongly with cognitive decline and leads to neuronal network dysfunction. Here, we aim to map the selective synaptic loss in hippocampal and parahippocampal subregions in AD and its association to the severity of neuropathology, axonal damage and cognitive decline.

Basic Science and Pathogenesis.

Background: Genome-Wide Association Studies (GWAS) have identified 86 SNPs associated with Alzheimer's disease (AD). GWAS-SNPs are markers of genetic variation in linkage disequilibrium (LD), which may drive the association with AD. One major class of genetic variation are Structural Variants (SVs), which can regulate transcription and translation of nearby genes.

Basic Science and Pathogenesis.

Background: Murine studies have identified blood proteins that influence brain aging, but translating these findings to humans remains challenging. We used an innovative approach to investigate whether genetically predicted blood levels of proteins linked to brain aging in animal models are associated with cognitive performance in individuals at risk of Alzheimer's disease (AD) [Figure 1].

Method: Through systematic review, we identified 13 circulating proteins with an aging/rejuvenating effect on the mouse brain.

Basic Science and Pathogenesis.

Background: SORL1 encodes the retromer-associated receptor SORLA that functions in endosomal recycling. Rare variants in SORL1 have been associated with Alzheimer's disease (AD) and rare pathogenic variants are estimated to occur in up to 2.75% of early onset AD patients and in 1.

Basic Science and Pathogenesis.

Background: The sortilin-related receptor 1 protein, SORL1, interacts with retromer to regulate trafficking of cargo out of the early endosome. Genetic variants in SORL1 that lead to a premature protein truncation (PTVs) are observed almost exclusively in Alzheimer's disease (AD) patients, suggesting SORL1's haploinsufficiency may be causal for AD. However, the large majority of SORL1 variants are rare missense variants which affect diverse structural domains, some of which may be causative for disease or (strongly) risk-increasing, while others are (likely) benign.

Basic Science and Pathogenesis.

Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare, hereditary cerebrovascular disease which causes stroke, complex migraine, and cognitive impairment. Given its monogenic nature, CADASIL is considered a 'pure' model of small vessel disease and vascular dementia. CADASIL is caused by NOTCH3 pathogenic variants with a broad resulting phenotypic spectrum.

Basic Science and Pathogenesis.

Background: The accumulation of misfolded tau proteins, an Alzheimer's disease (AD) hallmark, starts decades before the emergence of cognitive decline and clinical diagnosis. Autopsy studies support a predictable progression of tau pathology through large-scale systems. However, less is known about the specific progression patterns.

Basic Science and Pathogenesis.

Background: Amyotrophic lateral sclerosis (ALS) with only motor impairment (ALS-pure motor) and the behavioral variant of frontotemporal dementia (bvFTD) are hypothesized to be the extreme ends of the ALS-bvFTD spectrum. This spectrum also encompasses ALS patients with mild to severe cognitive impairment (ALSci) and/or behavioral impairment (ALSbi), including ALS with concomitant bvFTD. In a previous study, using magnetoencephalography (MEG), in early symptomatic ALS patients we showed resting-state functional connectivity changes in frontal, limbic and subcortical regions that overlap considerably with bvFTD.

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: Structural and functional changes of the choroid plexus (ChP) have been reported in Alzheimer's disease (AD). Nonetheless, the role of the ChP in the pathogenesis of AD remains largely unknown. We aim to unravel the relationship between ChP functioning and core AD pathogenesis using a unique proteomic approach in mice and humans.

Clinical Manifestations.

Background: With the increasing number of potential interventions for Alzheimer's Disease (AD), there is a growing need to detect meaningful cognitive changes early in the disease. Frequent passive monitoring of smartphone behaviour, such as typing speed and precision, can give insight into the cognitive changes in AD. In the 'A personalized Medicine Approach for AD' (ABOARD)-project we investigated the reliability and validity of typing behaviour to monitor cognition in people with and without AD.

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: The brainstem locus coeruleus (LC) is among the first sites of Alzheimer's disease (AD) pathology, accruing hyperphosphorylated tau as early as in young adulthood. Animal studies indicate that the LC is crucially involved in sleep-wake regulation, a recently established factor contributing to AD-related pathophysiological processes. However, the associations between LC integrity and sleep-wake phenotypes in the context of AD pathology remain poorly characterized in humans.

The impact of n-3 polyunsaturated fatty acids in patients with cancer: emerging themes.

Purpose Of Review: This review summarizes recent literature falling broadly under the topic of n-3 polyunsaturated fatty acids (PUFAs) in the oncology setting, highlighting emerging themes and emphasizing novel explorations.

Recent Findings: Meta-analyses continue to confirm safety and efficacy of n-3 PUFA supplementation on reducing inflammation and improving survival in people with cancer. Common themes in recent studies emphasize improving tumor-directed efficacy and reducing toxicities of common cancer therapies.

Clinical Manifestations.

Background: Surface dyslexia serves as a complementary feature in the classification of the semantic variant of Primary Progressive Aphasia (PPA), while reading deficits have also been reported in the other two PPA variants. In opaque languages, tasks involving regular and irregular words and non-words are useful tools for dyslexia diagnosis. However, in transparent languages like Spanish, where most words are regular for reading, different approaches are needed.

Clinical Manifestations.

Background: The Montreal Cognitive Assessment (MoCA) stands as a prominent cognitive impairment screening tool, finding widespread use globally and existing in official versions across 14 languages, including Spanish. Despite this, the challenges emerge due to the extensive variations within the Spanish language, which is not only the fourth most spoken language worldwide but also possesses significant geographic diversity, particularly evident in regions like Peru. Here, the intersection of regional nuances, low educational backgrounds, and culturally distinct tasks complicates the application of a standard MoCA version.

Clinical Manifestations.

Background: The Amsterdam Instrumental ADL Questionnaire (A-IADL-Q) has shown promising performance in detecting subtle impairment in IADL independency. Importantly, it has not been validated in older people in a primary care setting, i.e.

Clinical Manifestations.

Background: Alzheimer's disease (AD) causes increasing cognitive and functional impairments, and both are therefore important outcome measures for intervention studies. Cognition and everyday functioning are often used interchangeably, yet the extent of their relationship is still unclear. We therefore aim to assess the relationship between different cognitive domains and everyday functioning across the AD spectrum.

Clinical Manifestations.

Background: Automated analysis of natural speech is emerging as a promising digital biomarker of Alzheimer's disease (AD). As speech is a complex process, relying on multiple interacting cognitive functions, fine-grained analysis of speech may have the potential to capture subtle cognitive deficits in the very early stages of AD. Here, we examined the association between amyloid-beta (Aβ) pathology and acoustic speech characteristics in a group of cognitively normal Dutch adults.

Clinical Manifestations.

Background: Anosognosia, a hallmark of Alzheimer's disease (AD), manifests as a gradual decline in disease awareness, yet its neural correlates remain unclear. This study investigates how amyloid accumulation, glucose hypometabolism and cortical atrophy relate to cognitive awareness across the AD continuum. Both the pathological processes and the brain regions involved were studied.

Optical Excitation of Coherent THz Dynamics of the Rare-Earth Lattice through Resonant Pumping of f-f Electronic Transition in a Complex Perovskite DyFeO_{3}.

Resonant pumping of the electronic f-f transitions in the orbital multiplet of dysprosium ions (Dy^{3+}) in a complex perovskite DyFeO_{3} is shown to impulsively launch THz lattice dynamics corresponding to the B_{2g} phonon mode, which is dominanted by the motion of Dy^{3+} ions. The findings, supported by symmetry analysis and density-functional theory calculations, not only provide a novel route for highly selective excitation of the rare-earth crystal lattices but also establish important relationships between the symmetry of the electronic and lattice excitations in complex oxides.

R(3780) Resonance Interpreted as the 1^{3}D_{1}-Wave Dominant State of Charmonium from Precise Measurements of the Cross Section of e^{+}e^{-}→Hadrons.

We report the precise measurements of the cross section of e^{+}e^{-}→hadrons at center-of-mass energies from 3.645 to 3.871 GeV.

Effects of Patch Potentials in Electrostatic Double-Layer Forces.

We study the effects of patch potentials in the electrostatic double-layer force. In the limit of small potentials, we derive an analytic expression where the force is additive in terms of the Fourier components of the potential. Moreover, each term has a contribution of the same form as the standard double-layer force with an effective Debye length.

Clinical Manifestations.

Background: Verbal fluency, especially semantic fluency, may hold promise to predict clinical progression in the preclinical Alzheimer's disease (AD) stage, where patients show no objective cognitive impairment. We examined verbal fluency trajectories in amyloid-negative and amyloid-positive individuals with subjective cognitive decline (SCD), as well as whether baseline fluency characteristics (total scores and item-level) predicted progression to MCI or AD dementia.

Method: We retrospectively selected data of 471 Dutch individuals with SCD, with at least 1 follow-up fluency assessment, from the Amsterdam Dementia Cohort (Follow-up years = 4.