Developing Topics.

Background: Alzheimer's Disease (AD), a progressively worsening neurodegenerative disorder, impacts millions globally. Understanding its progression is crucial for developing effective interventions and management strategies. However, high variability in disease progression amongst individuals and the complexity of neuroimaging data pose significant challenges.

Developing Topics.

Background: Non-pharmacological interventions that improve cognitive functioning in patients with Alzheimer's disease will play a crucial role in the coming years to support their independence in daily living. Here, we investigated the potential of a novel smartphone-assisted real-world wayfinding training, tailored for older adults, to improve their spatial memory as one of the first cognitive functions affected by the disease. Spatial memory performance was assessed using a VR-based navigation task and the Gardony map drawing analyzer.

Alzheimer's Imaging Consortium.

Background: Amyloid PET imaging is an established diagnostic tool for Alzheimer's disease, but its successful integration into clinical practice requires a comprehensive understanding of its impact on patients and the healthcare system. In 2022, the coverage with evidence development (CED) ENABLE study has been approved by the German Federal Joint Committee (trial registration: DRKS00030839). The study is scheduled to start in early 2024.

Alzheimer's Imaging Consortium.

Background: Memory clinic patients typically present with Alzheimer's disease (AD) and cerebral small vessel disease (SVD) to varying degrees. Therefore, it is crucial to determine the etiology of cognitive deficits for facilitating patient-centered treatment in memory clinics. Plasma biomarkers (ptau217, Glial Fibrillary Acidic Protein [GFAP], Neurofilament light chain [NfL]) and fixel-based advanced diffusion MRI markers (fiber density, fiber-bundle cross-section) show potential towards disentangling AD- and SVD-related brain changes (Dewenter et al.

Alzheimer's Imaging Consortium.

Background: Training studies report beneficial effects of physical (PP) on cognitive performance (COG) in older adults, but are often accompanied by potentially biased parameters, conclusions, and lack of directionality. To address these issues, we used a dynamic Bayesian approach to analyse the dynamic session-to-session change and coupling of PP and COG over time.

Methods: We used two studies (N = 17 each): Study 1 contained 24-weeks (72 sessions) of training of older adults with suspected Alzheimer's disease (AD).

Alzheimer's Imaging Consortium.

Background: With a global ageing population, there is an increasing demand for fast and reliable early diagnosis of individuals. Convolutional neural networks (CNNs) have an immense potential in assisting clinicians in diagnosing dementia. Regional atrophy patterns, which are visible in T1-weighted MRI scans, have been consistently identified by the CNNs with high accuracy.

Alzheimer's Imaging Consortium.

Background: Despite evidence that sex can modulate Alzheimer's disease (AD) risk, whether risk factors are similarly related to AD markers in women and men remains largely unexplored. We aimed to assess how a combination of potentially modifiable risk factors are associated with cognitive and pathological markers of AD in older women and men.

Method: We included 135 cognitively unimpaired older adults ( = 65 years old, 83 women; Table 1) from the Age-Well trial (NCT02977819; baseline data) with multidomain assessments of modifiable risk factors, including cardiovascular (body mass index, systolic blood pressure, LDL cholesterol), lifestyle (complex mental activity throughout life, physical activity, diet), and psychological (quality of life, depressive and anxiety symptoms, rumination, worry).

Alzheimer's Imaging Consortium.

Background: There is a strong link between tau and progression of Alzheimer's disease (AD), necessitating an understanding of tau spreading mechanisms. Prior research, predominantly in typical AD, suggested that tau propagates from epicenters (regions with earliest tau) to functionally connected regions. However, given the constrained spatial heterogeneity of tau in typical AD, validating this connectivity-based tau spreading model in AD variants with distinct tau deposition patterns is crucial.

Alzheimer's Imaging Consortium.

Background: The posterior-medial network is crucial for episodic memory. However, the medial temporal lobe (MTL) and posteromedial cortex (PMC) regions are vulnerable to aging and early Alzheimer's disease (AD). Both processes might elicit distinct early functional connectivity (FC) changes which could be detrimental or protective/ compensatory regarding cognition.

Alzheimer's Imaging Consortium.

Background: The myelin sheath around axons is of fundamental importance for signal transduction. Myelin is reduced in white matter hyperintensities (WMH), which occur in both small vessel disease (SVD) and Alzheimer's disease (AD), giving rise to the question to what extent myelin is reduced in these diseases. Here, we employed an advanced MRI based method to assess myelin independently from a major confounding factor, i.

Alzheimer's Imaging Consortium.

Background: Neuroimaging studies have revealed age and sex-specific differences in Alzheimer's disease (AD) trajectories. However, how age and sex modulate tau spreading remains unclear. Thus, we investigated how age and sex modulate the amyloid-beta (Aß)-induced accumulation and spreading of tau pathology from local epicenters across connected brain regions.

Alzheimer's Imaging Consortium.

Background: While some memory decline in old age is "normal", there are some older individuals with maintained high cognitive performance. Using a multimodal approach including neuroimaging, fitness, genetic and questionnaire data (Fig1A), we aimed to identify factors that are related to successful cognitive aging and whether these differ between sexes.

Method: We analyzed 165 cognitively normal older adults age = 60 years from an ongoing study (SFB1436) (age = 71±8years, 43% female).

Alzheimer's Imaging Consortium.

Background: Alzheimer's disease (AD) is associated with substantial synaptic loss potentially due to synaptotoxicity of fibrillar tau, but the association between tau deposition and synaptic loss remains unclear. Based on previous observations that pathology spreads preferentially between closely connected regions, we tested in the current multi-PET tracer study the hypothesis that synaptic loss propagates to regions closely connected to epicenters of high tau accumulation.

Method: We assessed 18F-SynVesT-1 PET as a measure of synaptic vesicle glycoprotein 2A (SV2A), and 18F-flortaucipir tau-PET in fourty-five 18F-florbetapir-PET-positive (Aß+) subjects with MCI or AD dementia, and 23 cognitivly normal (CN) Aß- controls.

Alzheimer's Imaging Consortium.

Background: Differences in task-fMRI activation have recently been found to be related to neuropathological hallmarks of AD. However, the evolution of fMRI-based activation throughout AD disease progression and its relationship with other biomarkers remains elusive. Applying a disease progression model (DPM) to a multicentric cohort with up to four annual task-fMRI visits, we hope to provide a deeper insight into these relationships.

Alzheimer's Imaging Consortium.

Background: Analysis of neuroimaging data based on convolutional neural networks (CNNs) can improve detection of clinically relevant characteristics of patients with Alzheimer's disease (AD). Previously, our group developed a CNN-based approach for detecting AD via magnetic resonance imaging (MRI) scans and for identifying features that are relevant to the decision of the network. In the current study, we aimed to evaluate the potential utility of applying this approach to MRI scans to assist in the identification of individuals at high risk for amyloid positivity to aid in the selection of study samples and case finding for treatment.

Alzheimer's Imaging Consortium.

Background: Understanding modulators of Alzheimer's disease's (AD) progression is crucial for determining optimal treatment windows and targets. Apolipoprotein E e4 (ApoE4), i.e.

Alzheimer's Imaging Consortium.

Background: Memory clinic patients are a heterogeneous population representing various aetiologies of pathological aging. It is unknown if divergent spatiotemporal progression patterns of brain atrophy, as previously described in Alzheimer's disease (AD) patients, are prevalent and clinically meaningful in this group of older adults.

Method: To uncover atrophy subtypes, we applied the Subtype and Stage Inference (SuStaIn) algorithm to structural MRI data from 813 participants (mean ± SD age = 70.

Alzheimer's Imaging Consortium.

Background: In Alzheimer's disease (AD), cortical tau aggregation is a strong predictor of cortical brain atrophy as shown by MRI and PET studies, particularly driving the degeneration of neuronal somata in the grey matter. However, tau's physiological role is to stabilize microtubules within axons in the brain's white matter (WM) pathways. Therefore, tau's white-to-grey-matter translocation and aggregation in neurofibrillary tangles close to neuronal somata may induce WM degeneration through destabilization of axonal microtubule integrity.

Alzheimer's Imaging Consortium.

Background: In Alzheimer's disease, Aß triggers tau spreading which drives neurodegeneration and cognitive decline. However, the mechanistic link between Aß and tau remains unclear, which hinders therapeutic efforts to attenuate Aß-related tau accumulation. Preclinical research could show that tau spreads across connected neurons in an activity-dependent manner, and Aß was shown to trigger neuronal hyperactivity and hyperconnectivity.

Drug Development.

Numerous drugs (including disease-modifying therapies, cognitive enhancers and neuropsychiatric treatments) are being developed for Alzheimer's and related dementias (ADRD). Emerging neuroimaging modalities, and genetic and other biomarkers potentially enhance diagnostic and prognostic accuracy. These advances need to be assessed in real-world studies (RWS).

Dementia Care Research and Psychosocial Factors.

Background: Using artificial intelligence approaches enable automated assessment and analysis of speech biomarkers for Alzheimer's disease, for example using chatbot technology. However, current chatbots often are unsuitable for people with cognitive impairment. Here, we implemented a user-centred-design approach to evaluate and improve usability of a chatbot system for automated speech assessments for people with preclinical, prodromal and early dementia.

Dementia Care Research and Psychosocial Factors.

Background: Due to further development of diagnostic methods of early-stage diagnosis of Alzheimer's disease (AD) and new disease-modifying treatment options that require early diagnosis, a new focus on predictive and preventive medicine arises. With progress in AD dementia risk estimation, guidelines for counseling, considering individual aspects of those affected, are becoming more important. As part of the trinational project PreTAD (The Predictive Turn in Alzheimer's Disease: Ethical, Clinical, Linguistic and Legal Aspects) anticipated effects of AD dementia risk estimation for first-degree relatives of people with AD dementia are evaluated.

Dementia Care Research and Psychosocial Factors.

Background: Participatory research or patient and public involvement refer to the process of actively involving people with lived experience into the research process to improve its relevance, quality, and impact. In the PART project we aim to establish a sustainable structure to include underrepresented patient groups with neurodegenerative diseases into a patient advisory board for research. As one of our milestones, we conducted a systematic literature review with the aim of examining the impact of participatory research on people involved, such as those with cognitive impairment, caregivers, and researchers.

Dementia Care Research and Psychosocial Factors.

Background: Driven by (bio-)medical and technical developments, advanced non-invasive methods for estimating the risk of Alzheimer's dementia (ADD) are increasingly emerging. In the future, such methods could eventually become available for individuals in asymptomatic and preclinical stages of Alzheimer's disease (e.g.

Dementia Care Research and Psychosocial Factors.

Background: Environmental factors account for a considerable percentage of dementia cases. Studies in animal models have shown that environmental enrichment (EE; i.e.