Basic Science and Pathogenesis.

Background: Systemic inflammation in patients with Alzheimer's disease (AD) has been associated with an exacerbation in cognitive decline, but the underlying mechanisms remain largely unknown. In AD, intraneuronal hyperphosphorylated tau spreads through the brain via trans-synaptic prion-like propagation. Evidence suggests that propagation of tau pathology is linked to neuroinflammation.

Basic Science and Pathogenesis.

Background: Alzheimer's Disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline and memory loss. Early and accurate diagnosis of AD is crucial for patient information, advance planning, and potentially effective intervention and treatment. The integration of machine learning techniques with brain connectome graphs, encompassing both structural and functional brain connectomes, can enhance the accuracy and efficiency of AD diagnosis.

Basic Science and Pathogenesis.

Background: Diabetes increases the risk of Alzheimer's disease (AD), and mitochondrial dysfunction is implicated in both diseases. We previously detected mitochondrial DNA copy number (MtDNA-CN) changes in human parietal cortex that differed between diabetic AD and non-diabetic AD. We hypothesize that MtDNA-CN changes may be indicative of different underlying mechanisms.

Clinical Manifestations.

Background: Dementia-related biomarkers can detect pathology years before clinical diagnostic criteria are met. Understanding the relationship between biomarkers and early cognitive changes is crucial as disease-modifying therapies may have maximum benefits when delivered early. We aimed to demonstrate the utility of remote computerised cognitive tests in a large cohort of cognitively normal older individuals, comparing these to standard in-person assessments and investigating their associations with biomarkers.

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: Primary Progressive Aphasia (PPA) is a neurodegenerative disorder primarily affecting language abilities, with clinical variants (nonfluent/agrammatic variant [nfvPPA], semantic variant [svPPA], logopenic variant [lvPPA], and mixed-PPA [mPPA]) categorized based on linguistic features. This study aims to compare PPA cohorts of native speakers of two different languages: English (an analytic language with deep orthography) and Italian (a synthetic language with shallow orthography).

Methods: We considered 166 English participants (70 nfvPPA, 45 svPPA, 42 lvPPA, 9 mPPA) and 106 Italian participants (14 nfvPPA, 20 svPPA, 42 lvPPA, 31 mPPA).

Clinical Manifestations.

Background: Prior longitudinal studies among older adults have documented associations between hearing loss and changes in brain morphology. Whether interventions involving hearing aids can reduce age-related atrophy is unknown. A substudy within the Aging and Cognitive Health Evaluation in Elders (ACHIEVE, Clinicaltrials.

Clinical Manifestations.

Background: In Alzheimer's disease research, subjective report of cognitive and functional decline from participant-study partner (SP) dyads is an efficient method of assessing cognitive impairment and risk of clinical progression. The extent to which discordance (disagreement) between self- and SP-report is associated with diagnosis of cognitive impairment is not known.

Method: We tested the hypothesis that discordance between baseline self- and SP-report Everyday Cognition Scale (ECog) scores was associated with greater probability of mild cognitive impairment (MCI) diagnosis.

Clinical Manifestations.

Background: The Everyday Cognition questionnaire is a sensitive tool for measuring decline in activities of daily living and can differentiate dementia from normal cognition. There is limited data on comparing the ECog-12 performance by raters (self vs. informant/study-partner) and scoring systems (continuous average score vs.

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: To investigate the associations between courses of depression, the application of depression treatment, and the risk of incident dementia.

Method: In this prospective cohort study, 354,313 participants aged 50 to 70 years were recruited from the UK Biobank between 2006 and 2010, and were followed-up until 2020, with a total of 4,212,929 person-years. We initially studied the effect of depression on dementia incidence across four subgroups characterized by courses of depressive symptoms.

Clinical Manifestations.

Background: 'Dependence' has been proposed as a measurable health outcome reflecting the overall impact of disease progression in Alzheimer's disease (AD). However, the meaning and relevance of 'dependence' in early symptomatic AD (MCI and mild AD dementia) have not been previously investigated. Aims of the current research were to (1) explore the concept of 'dependence' from the perspective of caregivers of patients with early symptomatic AD, (2) assess the content validity of the Dependence Scale (DS; Stern, 1994), a 13-item scale evaluating patient dependence based on a caregiver interview, and (3) explore the relevance of newly incorporated DS rater guidance clarifying potential ambiguities in item phrasing.

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.

Clinical Manifestations.

Background: Epidemiological evidence regarding the association between cataract onset age and risk of incident dementia remains unexplored. To examine whether age at cataract diagnosis is associated with risk of incident dementia and its subtypes.

Methods: This prospective, population-based cohort study utilized data from the UK Biobank that collected baseline information between 2006 and 2010.

Clinical Manifestations.

Background: Dementia is associated with a range of non-cognitive features that can occur during the prodromal phase. Improved recognition of non-cognitive presentations of dementia could reduce inequalities in dementia diagnosis, particularly if sociocultural factors influence rates of help-seeking for cognitive symptoms. We aimed to investigate presentations to primary care in the years before dementia diagnosis in a deprived and ethnically diverse population with universal access to health care.

Clinical Manifestations.

Background: Sensitive screening for early Alzheimer's disease (AD)-related cognitive decline are needed. Prior research links high beta-amyloid (Aβ) levels to reduced proper name (PN) retrieval in individuals without cognitive impairment. We examined whether language-related regional tau from PET associated with Logical Memory (LM) proper name recall, accounting for LM covariates.

Clinical Manifestations.

Background: Remote unsupervised cognitive assessments have the potential to complement and facilitate cognitive assessment in clinical and research settings.

Method: Here we evaluate the usability, validity and reliability of unsupervised remote memory assessments via mobile devices (see Figure 1) in individuals without dementia from the Swedish BioFINDER-2 study and explore their prognostic utility regarding future cognitive decline in combination with a plasma marker for p-tau217.

Result: Usability was rated positively.

Clinical Manifestations.

Background: Frontotemporal degeneration (FTD) is a complex, heterogeneous group of fatal adult-onset disorders which lead to progressive dysfunction in behavior, motor symptoms, language, and/or cognition. While advances in research are cause for optimism, trials are hindered by the availability of participants. As FTD clinical trials typically require co-participation of a study partner, care partner perspectives on research are critical to understanding how to support recruitment and retention.

Clinical Manifestations.

Background: Assessments for early-stage Alzheimer's disease (AD) aim to identify neuropsychological and functional impairments, which rarely correlate with early disease stages. We need to enhance our understanding of the cognitive aspects contributing to functional decline to improve sensitivity in functional assessment. The ability to bind information in memory declines in preclinical AD stages.

Clinical Manifestations.

Background: Alzheimer's disease (AD) is associated with a range of non-cognitive symptoms that can be early or even presenting features. Better recognition of pre-diagnostic symptoms of AD would support improved early detection and diagnosis.

Method: To identify possible prodromal symptoms of AD, we systematically searched three electronic databases for prospective longitudinal studies to March 2023, that reported the risk of AD diagnosis associated with non-cognitive symptoms.

Basic Science and Pathogenesis.

Background: The "Recruitment and Retention for Alzheimer's Disease Diversity Genetic Cohorts in the ADSP (READD-ADSP)" is developing a resource to expand ancestral diversity in Alzheimer disease (AD) studies to dissect the genetic architecture of AD across different populations. In addition to US sites, READD-ADSP includes four US sites and nine countries in sub-Saharan Africa through the Africa Dementia Consortium (AfDC). The overall goal of READD-ADSP is to identify genetically driven targets in diverse groups including African Americans and Hispanic/Latinos in US, and Africans.

Clinical Manifestations.

Background: Speech and language impairments are associated with cognitive decline in neurodegenerative dementias, particularly Alzheimer's Disease (AD), where subtle speech changes may precede clinical dementia onset. As clinical trials prioritize early identification for disease-modifying treatments, digital biomarkers for timely screening become imperative. Digital speech-based biomarkers can be employed for screening populations at the earliest AD stages.

Induction of Epithelial-Mesenchymal Transition in Periodontitis Rat Model.

Objectives:  Epithelial-mesenchymal transition (EMT) is a process that shifts cellular phenotype. It is linked to several different inflammatory diseases including periodontitis. This study was conducted to investigate the involvement of the EMT process in an experimental periodontitis (EP) model.

Basic Science and Pathogenesis.

Background: Pathological alterations in Alzheimer's disease (AD) begin several years before the onset of symptoms. Grey matter mean diffusivity (MD) may be used as a measure of early grey matter damage in AD as it reflects the breakdown of microstructural barriers, which precede volumetric changes and affect cognitive function. In this study, we investigated the changes in MD early on in the disease trajectory, and relate them to the amyloid and tau deposition.

Clinical Manifestations.

Background: Patients with behavioural variant frontotemporal dementia (bvFTD) and right temporal variant frontotemporal dementia (rtvFTD) commonly exhibit abnormal hedonic and other behavioural responses to sounds, however hearing dysfunction in this disorder is poorly characterised. Here we addressed this issue using the Queen Square Tests of Auditory Cognition (QSTAC) - a neuropsychological battery for the systematic assessment of central auditory functions (including pitch pattern perception, environmental sound recognition, sound localisation and emotion processing) in cognitively impaired people.

Method: The QSTAC was administered to 12 patients with bvFTD, 7 patients with rtvFTD and 24 patients with comparator dementia syndromes (primary progressive aphasia and typical Alzheimer's disease) and 15 healthy age-matched individuals.