Biomarkers.

Background: The Centiloid method (CL) was introduced as a tracer-independent measure for cortical amyloid load and is now commonly used in Alzheimer's disease (AD) clinical trials. To facilitate its implementation into clinical settings, the AMYPAD consortium set out to integrate existing literature and recent work from the consortium to provide clinical context-of-use recommendations of the Centiloid scale, which has been submitted to the European Medicine Agency for endorsement as a Biomarker Qualification Opinion.

Method: Screening of the literature was performed on the 7/11/23 on PubMed to identify articles mentioning "Centiloid".

Biomarkers.

Background: Different patterns of atrophy exist in the dementia stage of AD. However, little is known about the heterogeneity of atrophy patterns and the mechanisms that drive subsequent propagation of the disease in the preclinical stages.

Method: From the AMYPAD-PNHS cohort, we included a total of 1323 non-demented individuals, including 1094 amyloid-negative, and 229 amyloid-positive participants (Table 1).

Biomarkers.

Background: With the development of disease modifying therapies targeting specific pathologies, accurate in vivo biomarkers have become increasingly important for disease classification. Recently, tests for neuronal α-synuclein (Lewy body) pathology have become available, complementing pre-existing tests for Alzheimer's disease (AD) pathology (Aβ and tau fluid and PET biomarkers) and vascular disease (MRI). Here, we aimed to identify and characterize data-driven pathology-based subtypes using these biomarkers.

Biomarkers.

Background: With the emergence of Alzheimer's disease (AD) disease-modifying therapies, identifying patients who could benefit from these treatments becomes critical. We evaluated whether a precise blood test could perform as well as established cerebrospinal fluid (CSF) tests in detecting amyloid-β (Aβ) plaques and tau tangles.

Method: Plasma %p-tau217 (ratio of phosporylated-tau217 to non-phosphorylated mid-region tau) was analyzed by mass spectrometry in the Swedish BioFINDER-2 cohort (n=1,422) and the US Knight ADRC cohort (n=337, Table 1).

Biomarkers.

Background: Accumulation of amyloid beta in the brain is one of the first events in Alzheimer's disease (AD) and starts decades before symptoms arise. It has been hypothesized that brain areas with higher levels of neuronal activation ('hubs') are more prone to amyloid deposition. In this study, we examined the regional relationship between cortical hubs and longitudinal changes in amyloid pathology in a sample of cognitively healthy older subjects.

Biomarkers.

Background: The Amyloid Imaging to Prevent Alzheimer's Disease (AMYPAD) Prognostic & Natural History Study (PNHS) is a prospective longitudinal PET cohort of over 1,500 non-demented individuals from 10 parent cohorts across Europe. We provide an overview of ongoing efforts to curate and integrate magnetic resonance imaging (MRI) multimodal images across sites and to extract biologically meaningful information (i.e.

Biomarkers.

Background: Identification of concomitant Lewy Body (LB) pathology might be important for the diagnostic and prognostic work-up of Alzheimer's disease (AD) in clinical practice and trials. Here, we aimed to determine whether the presence of LB pathology exacerbates AD-related disease progression.

Methods: Cognitively impaired (Mild Cognitive Impairment [MCI] and dementia, n=795) individuals from the ADNI cohort with available CSF α-synuclein amplification assay (SAA) and CSF p-tau/Aβ measures were included.

Biomarkers.

Background: Plasma levels of amyloid-β, and glial fibrillary acidic protein (GFAP) have demonstrated predictive potential for amyloid pathology in the early stages of Alzheimer's disease (AD) development. Utilizing baseline and up to 6-year follow-up plasma, positron emission tomography (PET) and cognitive data from cognitively unimpaired individuals, we here aim to test whether early changes in plasma biomarker levels associate with change in amyloid status and cognitive decline.

Methods: From the EMIF-AD PreclinAD study we selected individuals with normal cognition and longitudinal plasma, PET and cognitive data available (n=200, table 1).

Biomarkers.

Background: The emergence of disease-modifying drug therapies is expected to revolutionize the field of Alzheimer's disease (AD). Recent results from anti-amyloid clinical trials highlight the importance of early identification and accurate risk-stratification of individuals in early stages of the disease. In this context, the Amyloid Imaging to Prevent Alzheimer's Disease (AMYPAD) Prognostic and Natural History Study (PNHS) was established, leveraging existing cohorts to alleviate the burden of recruiting de novo participants.

Alzheimer's Imaging Consortium.

Background: The Amyloid Imaging to Prevent Alzheimer's Disease (AMYPAD) Prognostic & Natural History Study (PNHS) is a prospective longitudinal PET cohort of over 1,500 non-demented individuals from 10 parent cohorts across Europe. We provide an overview of ongoing efforts to curate and integrate magnetic resonance imaging (MRI) multimodal images across sites and to extract biologically meaningful information (i.e.

Alzheimer's Imaging Consortium.

Background: With the development of disease modifying therapies targeting specific pathologies, accurate in vivo biomarkers have become increasingly important for disease classification. Recently, tests for neuronal a-synuclein (Lewy body) pathology have become available, complementing pre-existing tests for Alzheimer's disease (AD) pathology (Aß and tau fluid and PET biomarkers) and vascular disease (MRI). Here, we aimed to identify and characterize data-driven pathology-based subtypes using these biomarkers.

Alzheimer's Imaging Consortium.

Background: Different patterns of atrophy exist in the dementia stage of AD. However, little is known about the heterogeneity of atrophy patterns and the mechanisms that drive subsequent propagation of the disease in the preclinical stages.

Method: From the AMYPAD-PNHS cohort, we included a total of 1323 non-demented individuals, including 1094 amyloid-negative, and 229 amyloid-positive participants (Table 1).

Centiloid recommendations for clinical context-of-use from the AMYPAD consortium.

Amyloid-PET quantification through the tracer-independent Centiloid (CL) scale has emerged as an essential tool for the accurate measurement of amyloid-β (Aβ) pathology in Alzheimer's disease (AD) patients. The AMYPAD consortium set out to integrate existing literature and recent work from the consortium to provide clinical context-of-use recommendations for the CL scale. Compared to histopathology, visual reads, and cerebrospinal fluid, CL quantification accurately reflects the amount of AD pathology.

Associations of life-course cardiovascular risk factors with late-life cerebral haemodynamics.

While the associations of mid-life cardiovascular risk factors with late-life white matter lesions (WMH) and cognitive decline have been established, the role of cerebral haemodynamics is unclear. We investigated the relation of late-life (69-71 years) arterial spin labelling (ASL) MRI-derived cerebral blood flow (CBF) with life-course cardiovascular risk factors (36-71 years) and late-life white matter hyperintensity (WMH) load in 282 cognitively healthy participants (52.8% female).

Quantification Supports Amyloid PET Visual Assessment of Challenging Cases: Results from the AMYPAD Diagnostic and Patient Management Study.

Several studies have demonstrated strong agreement between routine clinical visual assessment and quantification, suggesting that quantification approaches could support assessment by less experienced readers or in challenging cases. However, all studies to date have implemented a retrospective case collection, and challenging cases were generally underrepresented. We included all participants ( = 741) from the AMYPAD diagnostic and patient management study with available baseline amyloid PET quantification.

Association of Vascular Risk Factors and Cerebrovascular Pathology With Alzheimer Disease Pathologic Changes in Individuals Without Dementia.

Background And Objectives: Vascular risk factors (VRFs) and cerebral small vessel disease (cSVD) are common in patients with Alzheimer disease (AD). It remains unclear whether this coexistence reflects shared risk factors or a mechanistic relationship and whether vascular and amyloid pathologies have independent or synergistic influence on subsequent AD pathophysiology in preclinical stages. We investigated links between VRFs, cSVD, and amyloid levels (Aβ) and their combined effect on downstream AD biomarkers, that is, CSF hyperphosphorylated tau (P-tau), atrophy, and cognition.

Lewy body pathology exacerbates brain hypometabolism and cognitive decline in Alzheimer's disease.

Identifying concomitant Lewy body (LB) pathology through seed amplification assays (SAA) might enhance the diagnostic and prognostic work-up of Alzheimer's disease (AD) in clinical practice and trials. This study examined whether LB pathology exacerbates AD-related disease progression in 795 cognitively impaired individuals (Mild Cognitive Impairment and dementia) from the longitudinal multi-center observational ADNI cohort. Participants were on average 75 years of age (SD = 7.

The Early Perfusion Image Is Useful to Support the Visual Interpretation of Brain Amyloid-PET With 18F-Flutemetamol in Borderline Cases.

Purpose: Visual interpretation of brain amyloid-β (Aβ) PET can be difficult in individuals with borderline Aβ burden. Coregistration with individual MRI is recommended in these cases, which, however, is not always available. This study evaluated coregistration with the early perfusion frames acquired immediately after tracer injection to support the visual interpretation of the late Aβ-frames in PET with 18F-flutemetamol (FMM).

Digital remote assessment of speech acoustics in cognitively unimpaired adults: feasibility, reliability and associations with amyloid pathology.

Background: Digital speech assessment has potential relevance in the earliest, preclinical stages of Alzheimer's disease (AD). We evaluated the feasibility, test-retest reliability, and association with AD-related amyloid-beta (Aβ) pathology of speech acoustics measured over multiple assessments in a remote setting.

Methods: Fifty cognitively unimpaired adults (Age 68 ± 6.

Stress testing the Centiloid: Precision and variability of PET quantification of amyloid pathology.

Introduction: Assessing the potential sources of bias and variability of the Centiloid (CL) scale is fundamental for its appropriate clinical application.

Methods: We included 533 participants from AMYloid imaging to Prevent Alzheimer's Disease (AMYPAD DPMS) and Alzheimer's Disease Neuroimaging Initiative (ADNI) cohorts. Thirty-two CL pipelines were created using different combinations of reference region (RR), RR and target types, and quantification spaces.

Amyloid-PET imaging predicts functional decline in clinically normal individuals.

Background: There is good evidence that elevated amyloid-β (Aβ) positron emission tomography (PET) signal is associated with cognitive decline in clinically normal (CN) individuals. However, it is less well established whether there is an association between the Aβ burden and decline in daily living activities in this population. Moreover, Aβ-PET Centiloids (CL) thresholds that can optimally predict functional decline have not yet been established.

Continuous β-Amyloid CSF/PET Imbalance Model to Capture Alzheimer Disease Heterogeneity.

Background And Objectives: Discordance between CSF and PET biomarkers of β-amyloid (Aβ) might reflect an imbalance between soluble and aggregated species, possibly reflecting disease heterogeneity. Previous studies generally used binary cutoffs to assess discrepancies in CSF/PET biomarkers, resulting in a loss of information on the extent of discordance. In this study, we (1) jointly modeled Aβ-CSF/PET data to derive a continuous measure of the imbalance between soluble and fibrillar pools of Aβ, (2) investigated factors contributing to this imbalance, and (3) examined associations with cognitive trajectories.