Basal forebrain global functional connectivity is preserved in asymptomatic presenilin-1 E280A mutation carriers: Results from the Colombia cohort.

Background: Imaging studies showed early atrophy of the cholinergic basal forebrain in prodromal sporadic Alzheimer's disease and reduced posterior basal forebrain functional connectivity in amyloid positive individuals with subjective cognitive decline. Similar investigations in familial cases of Alzheimer's disease are still lacking.

Objectives: To test whether presenilin-1 E280A mutation carriers have reduced basal forebrain functional connectivity and whether this is linked to amyloid pathology.

Timing of risk factors, prodromal features, and comorbidities of dementia from a large health claims case-control study.

Background: Many risk factors for dementia have been identified, but the timing of risk is less well understood. Here, we analyzed risk factors in a case-control study covering 10 years before an incident dementia diagnosis.

Methods: We designed a case-control study using insurance claims of outpatient consultations of patients with German statutory health insurance between January 1, 2012, and December 31, 2022.

Modifiable risk factors and symptom progression in dementia over up to 8 years-Results of the DelpHi-MV trial.

Introduction: This study investigated the association between modifiable factors and symptom progression in dementia over up to 8 years.

Methods: Multilevel growth curve models assessed the role of modifiable risk factors (low education, hearing impairment and its treatment, depression, physical inactivity, diabetes and its treatment, smoking, hypertension and its treatment, obesity, alcohol consumption, social isolation, and visual impairment) on cognitive and functional trajectories in 353 people with dementia.

Results: Higher education was associated with higher initial cognitive status but faster decline.

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.

Environmental enrichment is associated with favorable memory-related functional brain activity patterns in older adults.

Background: In humans, environmental enrichment (EE), as measured by the engagement in a variety of leisure activities, has been associated with larger hippocampal structure and better memory function. The present cross-sectional study assessed whether EE during early life (13-30 years) and midlife (30-65 years) is associated with better preserved memory-related brain activity patterns in older age.

Methods: In total, 372 cognitively unimpaired older adults (aged ≥60 years old) of the DZNE-Longitudinal Study on Cognitive Impairment and Dementia (DELCODE; DRKS00007966) were investigated.

Brain age in genetic and idiopathic Parkinson's disease.

The brain-age gap, i.e. the difference between the brain age estimated from structural MRI data and the chronological age of an individual, has been proposed as a summary measure of brain integrity in neurodegenerative diseases.

Artificial intelligence-based rapid brain volumetry substantially improves differential diagnosis in dementia.

Introduction: This study evaluates the clinical value of a deep learning-based artificial intelligence (AI) system that performs rapid brain volumetry with automatic lobe segmentation and age- and sex-adjusted percentile comparisons.

Methods: Fifty-five patients-17 with Alzheimer's disease (AD), 18 with frontotemporal dementia (FTD), and 20 healthy controls-underwent cranial magnetic resonance imaging scans. Two board-certified neuroradiologists (BCNR), two board-certified radiologists (BCR), and three radiology residents (RR) assessed the scans twice: first without AI support and then with AI assistance.

Blood-based quantification of Aβ oligomers indicates impaired clearance from brain in ApoE ε4 positive subjects.

Background: Quantification of Amyloid beta (Aβ) oligomers in plasma enables early diagnosis of Alzheimer's Disease (AD) and improves our understanding of underlying pathologies. However, quantification necessitates an extremely sensitive and selective technology because of very low Aβ oligomer concentrations and possible interference from matrix components.

Methods: In this report, we developed and validated a surface-based fluorescence distribution analysis (sFIDA) assay for quantification of Aβ oligomers in plasma.

Documentation of prodromal features and risk factors of dementia disease in primary care practice.

Background: Documented risk factors and prodromal features of dementia in primary care practices may support dementia prevention and early detection in routine care.

Objective: To identify documented prodromal features and risk factors of dementia before the incident dementia diagnosis in German primary care practices.

Methods: This case-control study used documented diagnoses (risk factors, prodromal features) and prescriptions of primary care practices for 73,717 patients with dementia disease and 73,717 matched controls (ratio 1:1).

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.

Perivascular space enlargement accelerates in ageing and Alzheimer's disease pathology: evidence from a three-year longitudinal multicentre study.

Background: Perivascular space (PVS) enlargement in ageing and Alzheimer's disease (AD) and the drivers of such a structural change in humans require longitudinal investigation. Elucidating the effects of demographic factors, hypertension, cerebrovascular dysfunction, and AD pathology on PVS dynamics could inform the role of PVS in brain health function as well as the complex pathophysiology of AD.

Methods: We studied PVS in centrum semiovale (CSO) and basal ganglia (BG) computationally over three to four annual visits in 503 participants (255 females; mean = 70.

Longitudinal evidence for a mutually reinforcing relationship between white matter hyperintensities and cortical thickness in cognitively unimpaired older adults.

Background: For over three decades, the concomitance of cortical neurodegeneration and white matter hyperintensities (WMH) has sparked discussions about their coupled temporal dynamics. Longitudinal studies supporting this hypothesis nonetheless remain scarce.

Methods: We applied global and regional bivariate latent growth curve modelling to determine the extent to which WMH and cortical thickness were interrelated over a four-year period.

Loss of the ipsilateral silent period in amyotrophic lateral sclerosis is associated with reduced white matter integrity in the motor section of the corpus callosum.

Objective: Interhemispheric neurons in the motor section of the corpus callosum have an inhibitory effect on neurons of the contralateral motor cortex. Three quarters of patients with amyotrophic laterals sclerosis (ALS) show impaired transcallosal inhibition. We aimed to investigate whether structural changes co-occur with this functional impairment and to explore its phenotypic correlates.

Fully Automated MRI-based Analysis of the Locus Coeruleus in Aging and Alzheimer's Disease Dementia using ELSI-Net.

Introduction: The Locus Coeruleus (LC) is linked to the development and pathophysiology of neurodegenerative diseases such as Alzheimer's Disease (AD). Magnetic Resonance Imaging based LC features have shown potential to assess LC integrity in vivo.

Methods: We present a Deep Learning based LC segmentation and feature extraction method: ELSI-Net and apply it to healthy aging and AD dementia datasets.

Facilitating the use of the target product profile in academic research: a systematic review.

Background: The Target Product Profile (TPP) is a tool used in industry to guide development strategies by addressing user needs and fostering effective communication among stakeholders. However, they are not frequently used in academic research, where they may be equally useful. This systematic review aims to extract the features of accessible TPPs, to identify commonalities and facilitate their integration in academic research methodology.

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.

Ethics, design, and implementation criteria of digital assistive technologies for people with dementia from a multiple stakeholder perspective: a qualitative study.

Background: Dementia impairs the ability of people with dementia to be autonomous and independent. They need support from third parties, who should ideally respect their autonomy and independence as much as possible. Supporting people with dementia can be very burdensome for caregivers and numbers of patients increase while numbers of potential caregivers decline.

Contrastive Self-supervised Learning for Neurodegenerative Disorder Classification.

Neurodegenerative diseases such as Alzheimer's disease (AD) or frontotemporal lobar degeneration (FTLD) involve specific loss of brain volume, detectable in vivo using T1-weighted MRI scans. Supervised machine learning approaches classifying neurodegenerative diseases require diagnostic-labels for each sample. However, it can be difficult to obtain expert labels for a large amount of data.

Clinical Outcomes and Cost-Effectiveness of Collaborative Dementia Care: A Secondary Analysis of a Cluster Randomized Clinical Trial.

Importance: Long-term evidence for the effectiveness and cost-effectiveness of collaborative dementia care management (CDCM) is lacking.

Objective: To evaluate whether 6 months of CDCM is associated with improved patient clinical outcomes and caregiver burden and is cost-effective compared with usual care over 36 months.

Design, Setting, And Participants: This was a prespecified secondary analysis of a general practitioner (GP)-based, cluster randomized, 2-arm clinical trial conducted in Germany from January 1, 2012, to December 31, 2014, with follow-up until March 31, 2018.