Long-term retrieval performance is associated with CA1 hippocampal volume in older adults and individuals at risk for dementia.

Background: Long-term retrieval (LTR) and accelerated long-term forgetting (ALF) paradigms might help differentiating individuals at increased dementia risk from healthy controls (HC).

Objective: We investigated the utility of a LTR paradigm in discriminating subjective cognitive decline (SCD) from HC and its relationship to the CA1 body volume, a hippocampal structure pivotal to the memory circuitry.

Methods: LTR was assessed via recall rates of the ADAS-cog word list and the FCSRT-IR free recall in 59 DELCODE study participants, including individuals with SCD and mild cognitive impairment (MCI), as well as HC, all of them DELCODE study participants.

Polygenic Hazard Score for Predicting Age-associated Risk of Alzheimer's Disease in European Populations: Development and Validation.

Objectives: Polygenic hazard score (PHS) models can be used to predict the age-associated risk for complex diseases, including Alzheimer's disease (AD). In this study, we present an improved PHS model for AD that incorporates a large number of genetic variants and demonstrates enhanced predictive accuracy for age of onset in European populations compared to alternative models.

Methods: We used the genotyped European Alzheimer & Dementia Biobank (EADB) sample (n=42,120) to develop and evaluate the performance of the PHS model.

Disease stage-specific atrophy markers in Alzheimer's disease.

Introduction: Structural magnetic resonance imaging (MRI) often lacks diagnostic, prognostic, and monitoring value in Alzheimer's disease (AD), particularly in early disease stages. To improve its utility, we aimed to identify optimal atrophy markers for different intended uses.

Methods: We included 363 older adults; cognitively unimpaired individuals who were negative or positive for amyloid beta (Aβ) and Aβ-positive patients with subjective cognitive decline, mild cognitive impairment, or dementia of the Alzheimer type.

Associations between digital speech features of automated cognitive tasks and trajectories of brain atrophy and cognitive decline in early Alzheimer's disease.

BackgroundSpeech-based features extracted from telephone-based cognitive tasks show promise for detecting cognitive decline in prodromal and manifest dementia. Little is known about the cerebral underpinnings of these speech features.ObjectiveTo examine associations between speech features, brain atrophy, and longitudinal cognitive decline in individuals at risk for Alzheimer's disease (AD).

The effect of cognition and age on the efficacy of psychotherapy in late-life depression.

Background: Cognitive impairment is prevalent in older age and in patients with depression, which may limit the efficacy of psychotherapy for late-life depression (LLD). We analyzed the effect of age and baseline cognition on the efficacy of psychotherapy in LLD.

Methods: This secondary analysis of a randomized controlled multicenter study included 213 participants (60-92 years) with moderate to severe depression who had received either supportive psychotherapy (SUI) or an LLD-specific cognitive behavioral therapy (LLD-CBT), both of which led to a substantial reduction in depressive symptoms.

Depressive symptom factors and their differential association with psychotherapy outcomes in late-life depression: Results of the CBTlate study.

Objective: Depression is characterized by heterogeneous symptom patterns. We investigated different facets of depressive symptoms and their role in predicting the longitudinal outcome of psychotherapy in late-life depression (LLD).

Methods: This is a secondary analysis of a multicenter, randomized clinical trial in 229 LLD patients.

Mini social cognition and emotional assessment: Diagnostic performance and neural correlates in behavioural-variant frontotemporal dementia.

We aimed at validating the Mini Social Cognition and Emotional Assessment (Mini-SEA) in a German cohort of mildly impaired behavioural-variant frontotemporal dementia (bvFTD) patients and healthy controls. The Mini-SEA comprises the Facial Emotion Recognition Test (FERT) and the Faux Pas Test (FPT) measuring Theory of Mind (ToM) abilities in social norm-related real-life stories. We examined the diagnostic performance of the Mini-SEA alongside other neuropsychological assessments and investigated its structural neural correlates.

GWAS meta-analysis of CSF Alzheimer's disease biomarkers 18,948 individuals reveal novel loci and genes regulating lipid metabolism, brain volume and autophagy.

Cerebrospinal fluid (CSF) amyloid beta (Aβ42), total tau (t-tau), and phosphorylated tau (p-tau181) are well accepted markers of Alzheimer's disease. We performed a GWAS meta-analysis including 18,948 individuals of European and 416 non-European ancestry. We identified 12 genome-wide significant loci across all three biomarkers, eight of them novel.

Speech-based digital cognitive assessments for detection of mild cognitive impairment: Validation against paper-based neurocognitive assessment scores.

BackgroundCognitive decline in Alzheimer's disease (AD) often includes speech impairments, where subtle changes may precede clinical dementia onset. As clinical trials focus on early identification of patients for disease-modifying treatments, digital speech-based assessments for scalable screening have become crucial.ObjectiveThis study aimed to validate a remote, speech-based digital cognitive assessment for mild cognitive impairment (MCI) detection through the comparison with gold-standard paper-based neurocognitive assessments.

Blood biomarkers confirm subjective cognitive decline (SCD) as a distinct molecular and clinical stage within the NIA-AA framework of Alzheimer´s disease.

Subjective cognitive decline (SCD) is proposed as an indicator of transitional disease stage 2 in the Alzheimer's disease (AD) continuum. However, molecular and particularly longitudinal fluid biomarker data for this stage are still limited. This study aimed to determine whether blood-based biomarkers in amyloid-positive individuals with SCD (A + SCD) support the notion of stage 2 as a distinct stage between stages 1 and 3 of AD and to identify those at high risk for clinical progression.

Disease stage-specific atrophy markers in Alzheimer's disease.

Introduction: Structural MRI often lacks diagnostic, prognostic, and monitoring value in Alzheimer's disease (AD), particularly in early disease stages. To improve its utility, we aimed to identify optimal MRI readouts for different use cases.

Methods: We included 363 older adults; healthy controls (HC) who were negative or positive for amyloidbeta (Aβ) and Aβ-positive patients with subjective cognitive decline (SCD), mild cognitive impairment, or dementia of the Alzheimer type.

CSF biomarkers are differentially linked to brain areas high and low in noradrenaline, dopamine and serotonin across the Alzheimer's disease spectrum.

Neurotransmitter systems of noradrenaline, dopamine, serotonin and acetylcholine are implicated in cognitive functions such as memory, learning and attention and are known to be altered in neurodegenerative diseases like Alzheimer's disease. Specific brain structures involved in these systems, e.g.

Linking higher amyloid beta 1-38 (Aβ(1-38)) levels to reduced Alzheimer's disease progression risk.

Introduction: The beneficial effects of amyloid beta 1-38, or Aβ(1-38), on Alzheimer's disease (AD) progression in humans in vivo remain controversial. We investigated AD patients' cerebrospinal fluid (CSF) Aβ(1-38) and AD progression.

Methods: Cognitive function and diagnostic change were assessed annually for 3 years in 177 Aβ-positive participants with subjective cognitive decline (SCD), mild cognitive impairment (MCI), and dementia from the German Center for Neurodegenerative Diseases (DZNE) longitudinal cognitive impairment and dementia study (DELCODE) cohort using the Mini-Mental State Examination (MMSE), Preclinical Alzheimer's Cognitive Composite (PACC), Clinical Dementia Rating (CDR), and National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria.

Locus coeruleus signal intensity and emotion regulation in agitation in Alzheimer's disease.

Hyperphosphorylated tau accumulation is seen in the noradrenergic locus coeruleus from the earliest stages of Alzheimer's disease onwards and has been associated with symptoms of agitation. It is hypothesized that compensatory locus coeruleus-noradrenaline system overactivity and impaired emotion regulation could underlie agitation propensity, but to our knowledge this has not previously been investigated. A better understanding of the neurobiological underpinnings of agitation would help the development of targeted prevention and treatment strategies.

Cognitive reserve against Alzheimer's pathology is linked to brain activity during memory formation.

The cognitive reserve (CR) hypothesis posits that individuals can differ in how their brain function is disrupted by pathology associated with aging and neurodegeneration. Here, we test this hypothesis in the continuum from cognitively normal to at-risk stages for Alzheimer's Disease (AD) to AD dementia using longitudinal data from 490 participants of the DELCODE multicentric observational study. Brain function is measured using task fMRI of visual memory encoding.

Prognostic value of Alzheimer's disease plasma biomarkers in the oldest-old: a prospective primary care-based study.

Background: Blood-based biomarkers offer a promising, less invasive, and more cost-effective alternative for Alzheimer's disease screening compared to cerebrospinal fluid or imaging biomarkers. However, they have been extensively studied only in memory clinic-based cohorts. We aimed to validate them in a more heterogeneous, older patient population from primary care.

Amyloid and SCD jointly predict cognitive decline across Chinese and German cohorts.

Introduction: Subjective cognitive decline (SCD) in amyloid-positive (Aβ+) individuals was proposed as a clinical indicator of Stage 2 in the Alzheimer's disease (AD) continuum, but this requires further validation across cultures, measures, and recruitment strategies.

Methods: Eight hundred twenty-one participants from SILCODE and DELCODE cohorts, including normal controls (NC) and individuals with SCD recruited from the community or from memory clinics, underwent neuropsychological assessments over up to 6 years. Amyloid positivity was derived from positron emission tomography or plasma biomarkers.

Plasma amyloid beta X-42/X-40 ratio and cognitive decline in suspected early and preclinical Alzheimer's disease.

Introduction: Blood-based biomarkers are a cost-effective and minimally invasive method for diagnosing the early and preclinical stages of amyloid positivity (AP). Our study aims to investigate our novel immunoprecipitation-immunoassay (IP-IA) as a test for predicting cognitive decline.

Methods: We measured levels of amyloid beta (Aβ)X-40 and AβX-42 in immunoprecipitated eluates from the DELCODE cohort.

Age-specific risk factors of depression among the oldest-old - evidence from the multicenter AgeCoDe-AgeQualiDe study.

Purpose: The present study aimed to investigate age-group-specific incidence rates and risk factors for depressive symptoms in the highest age groups.

Methods: Data were derived from a prospective multicenter cohort study conducted in primary care - the AgeCoDe/AgeQualiDe study. In total, 2,436 patients 75 years and older were followed from baseline to ninth follow-up.

Plasma extracellular vesicle tau and TDP-43 as diagnostic biomarkers in FTD and ALS.

Minimally invasive biomarkers are urgently needed to detect molecular pathology in frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Here, we show that plasma extracellular vesicles (EVs) contain quantifiable amounts of TDP-43 and full-length tau, which allow the quantification of 3-repeat (3R) and 4-repeat (4R) tau isoforms. Plasma EV TDP-43 levels and EV 3R/4R tau ratios were determined in a cohort of 704 patients, including 37 genetically and 31 neuropathologically proven cases.

Symptomatic Clusters Related to Amyloid Positivity in Cognitively Unimpaired Individuals.

Background: The NIA-AA Research Framework on Alzheimer's disease (AD) proposes a transitional stage (stage 2) characterized by subtle cognitive decline, subjective cognitive decline (SCD) and mild neurobehavioral symptoms (NPS).

Objective: To identify participant clusters based on stage 2 features and assess their association with amyloid positivity in cognitively unimpaired individuals.

Methods: We included baseline data of N = 338 cognitively unimpaired participants from the DELCODE cohort with data on cerebrospinal fluid biomarkers for AD.