Is early-phase amyloid PET ready for use as neurodegeneration marker?

Alzheimer's disease is marked by accumulation of amyloid-β (Aβ) and abnormal tau, associated with subsequent neurodegeneration. Validated markers of neurodegeneration include brain glucose metabolism, perfusion and atrophy. Dual-phase amyloid PET imaging allows to assess both Aβ buildup and perfusion changes through a single tracer injection.

Comparison of two preprocessing methods for F-Flortaucipir PET quantification in Alzheimer's disease.

Background: Tau-Positron Emission Tomography (PET) has become central in Alzheimer's disease (AD) research and clinical settings. Multiple preprocessing pipelines for tau-PET quantification have been described, with satisfactory performance but direct comparisons remain scarse. Our study evaluates the comparability of two commonly used PET preprocessing methods, respectively in native and standard spaces, in quantifying tau deposition and in their ability to discriminate AD patients.

Validating the Amyloid Cascade Through the Revised Criteria of Alzheimer's Association Workgroup 2024 for Alzheimer Disease.

Background And Objectives: The amyloid cascade hypothesis posits that Alzheimer disease (AD) progresses from amyloid deposition to tau deposition, neurodegeneration, and eventually cognitive impairment and is the foundation of the revised criteria of Alzheimer's Association Workgroup 2024 (AA-2024). To account for copathologies and cognitive resilience that affect the penetrance of the AD cascade, AA-2024 introduced a 2-dimensional biological-clinical staging framework. We aimed to estimate the proportion of persons along the AD continuum whose biological and clinical trajectories align with the amyloid cascade.

Memory network and cognitive reserve are associated with preserved and stimulated cholinergic neurotransmission.

The cholinergic system plays a central role in cognition and neural function, and, in Alzheimer disease (AD) and Lewy body disease (LBD), it has profound implications for cognitive impairment and dementia. The cholinergic forebrain pathway, innervating the neocortex and limbic system, is crucial for learning, memory, and other essential aspects of cognition and plays a wider role in promoting neuronal plasticity. Given the neuroplasticity processes characterizing the cholinergic regions, this system may be sensitive to modulatory phenomena such as cognitive reserve (CR).

Sex differences in the association of Alzheimer's disease biomarkers and cognition in a multicenter memory clinic study.

Background: This study investigated sex differences in the associations between Alzheimer's disease (AD) biomarkers, cognitive performance, and decline in memory clinic settings.

Methods: 249 participants (females/males:123/126), who underwent tau-PET, amyloid-PET, structural MRI, and plasma glial fibrillary acidic protein (GFAP) measurement were included from Geneva and Lausanne Memory Clinics. Mann-Whitney U tests investigated sex differences in clinical and biomarker data.

Early-phase F-Flortaucipir tau-PET as a proxy of brain metabolism in Alzheimer's disease: a comparison with F-FDG-PET and early-phase amyloid-PET.

Purpose: As dual-phase amyloid-PET can evaluate amyloid (A) and neurodegeneration (N) with a single tracer injection, dual-phase tau-PET might be able to provide both tau (T) and N. Our study aims to assess the association of early-phase tau-PET scans and F-fluorodeoxyglucose (FDG) PET and their comparability in discriminating Alzheimer's disease (AD) patients and differentiating neurodegenerative patterns.

Methods: 58 subjects evaluated at the Geneva Memory Center underwent dual-phase F-Flortaucipir-PET with early-phase acquisition (eTAU) and F-FDG-PET within 1 year.

In Vivo Tau and Neurodegeneration Imaging in a Family With the Presenilin 1 Met146Leu Pathogenic Variant.

Objectives: We investigated tau and neurodegeneration patterns and clinical phenotypes in carriers of a specific pathogenic variant in the PSEN1 gene and 1 nonaffected relative.

Methods: We included 3 symptomatic carriers of the c.436 A>C, p.

Association of glial fibrillary acid protein, Alzheimer's disease pathology and cognitive decline.

Increasing evidence shows that neuroinflammation is a possible modulator of tau spread effects on cognitive impairment in Alzheimer's disease. In this context, plasma levels of the glial fibrillary acidic protein (GFAP) have been suggested to have a robust association with Alzheimer's disease pathophysiology. This study aims to assess the correlation between plasma GFAP and Alzheimer's disease pathology, and their synergistic effect on cognitive performance and decline.

Neuroimaging-guided diagnosis of possible FTLD-FUS pathology: a case report.

Background: This case report presents a patient with progressive memory loss and choreiform movements.

Case Presentation: Neuropsychological tests indicated multi-domain amnestic mild cognitive impairment (aMCI), and neurological examination revealed asymmetrical involuntary hyperkinetic movements. Imaging studies showed severe left-sided atrophy and hypometabolism in the left frontal and temporoparietal cortex.

The diagnostic and prognostic value of tau-PET in amnestic MCI with different FDG-PET subtypes.

Objectives: Mild cognitive impairment presenting with an amnestic syndrome (aMCI) and amyloid positivity is considered due to AD. Many subjects, however, can show an overall very slow progression relevant for differential diagnosis, prognosis, and treatment. This study assessed PET biomarkers, including brain glucose metabolism, tau, and amyloid load, in a series of comparable aMCI at baseline, clinically evaluated at follow-up.

Distinctive clinical and imaging trajectories in SWEDD and Parkinson's disease patients.

A proportion of patients clinically diagnosed with Parkinson's disease (PD) can have a I-FP-CIT-SPECT scan without evidence of dopaminergic deficit (SWEDD), generating a debate about the underlying biological mechanisms. This study investigated differences in clinical features, I-FP-CIT binding, molecular connectivity, as well as clinical and imaging progression between SWEDD and PD patients. We included 36 SWEDD, 49 de novo idiopathic PD, and 49 healthy controls with I-FP-CIT-SPECT from the Parkinson's Progression Markers Initiative.

Heterogeneity and overlap in the continuum of linguistic profile of logopenic and semantic variants of primary progressive aphasia: a Profile Analysis based on Multidimensional Scaling study.

Background: Primary progressive aphasia (PPA) diagnostic criteria underestimate the complex presentation of semantic (sv) and logopenic (lv) variants, in which symptoms partially overlap, and mixed clinical presentation (mixed-PPA) and heterogenous profile (lvPPA +) are frequent. Conceptualization of similarities and differences of these clinical conditions is still scarce.

Methods: Lexical, semantic, phonological, and working memory errors from nine language tasks of sixty-seven PPA were analyzed using Profile Analysis based on Multidimensional Scaling, which allowed us to create a distributed representation of patients' linguistic performance in a shared space.

Mapping brain metabolism, connectivity and neurotransmitters topography in early and late onset dementia with lewy bodies.

Introduction: Early-onset dementia with Lewy bodies (EO-DLB) is associated with rapid cognitive decline and severe neuropsychiatric symptoms at onset.

Methods: Using FDG-PET imaging for 62 patients (21 EO-DLB, 41 LO (late-onset)-DLB), we explored brain hypometabolism, and metabolic connectivity in the whole-brain network and resting-state networks (RSNs). We also evaluated the spatial association between brain hypometabolism and neurotransmitter pathways topography.

A comparison of visual assessment and semi-quantification for the diagnostic and prognostic use of [F]flortaucipir PET in a memory clinic cohort.

Purpose: [F]Flortaucipir PET is a powerful diagnostic and prognostic tool for Alzheimer's disease (AD). Tau status definition is mainly based in the literature on semi-quantitative measures while in clinical settings visual assessment is usually preferred. We compared visual assessment with established semi-quantitative measures to classify subjects and predict the risk of cognitive decline in a memory clinic population.

The impact of tau deposition and hypometabolism on cognitive impairment and longitudinal cognitive decline.

Introduction: Tau and neurodegeneration strongly correlate with cognitive impairment, as compared to amyloid. However, their contribution in explaining cognition and predicting cognitive decline in memory clinics remains unclarified.

Methods: We included 94 participants with Mini-Mental State Examination (MMSE), tau positron emission tomography (PET), amyloid PET, fluorodeoxyglucose (FDG) PET, and MRI scans from Geneva Memory Center.

Comparing two picture naming tasks in primary progressive aphasia: Insights from behavioural and neural results.

Picture naming tests are widely used to evaluate language impairments in neurodegenerative diseases, especially in Primary Progressive Aphasia (PPA). The available tests differ for many factors affecting the performance, e.g.

Sex differences in brain metabolic connectivity architecture in probable dementia with Lewy bodies.

We investigated how sex modulates metabolic connectivity alterations in probable dementia with Lewy bodies (pDLB). We included 131 pDLB patients (males/females: 58/73) and similarly aged healthy controls (HC) (male/female: 59/75) with available (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) scans. We assessed (1) sex differences in the whole-brain connectivity, identifying pathological hubs, (2) connectivity alterations in functional pathways of the neurotransmitter systems, (3) Resting State Networks (RSNs) integrity.

Sex differences in dementia with Lewy bodies: an imaging study of neurotransmission pathways.

Purpose: Dementia with Lewy bodies (DLB) is characterized by a wide clinical and biological heterogeneity, with sex differences reported in both clinical and pathologically confirmed DLB cohorts. No research evidence is available on sex differences regarding molecular neurotransmission. This study aimed to assess whether sex can influence neurotransmitter systems in patients with probable DLB (pDLB).

Manual and semi-automated approaches to MIBG myocardial scintigraphy in patients with Parkinson's disease.

Objective: This study investigates the effects of manual and semi-automatic methods for assessing MIBG semi-quantitative indices in a clinical setting.

Materials And Methods: We included I-MIBG scans obtained in 35 patients with idiopathic Parkinson's Disease. Early and late heart-to-mediastinum (H/M) ratios were calculated from I-MIBG images using regions of interest (ROIs) placed over the heart and the mediastinum.

Comprehensive qualitative characterization of linguistic performance profiles in primary progressive aphasia: a multivariate study with FDG-PET.

Primary progressive aphasia (PPA) classification relies on profile characterization of quantitatively impaired/spared performance in language tasks. In this study, we coextracted 8 qualitative types of errors in 67 PPA patients submitted to a comprehensive language assessment. Canonical correlation analysis was applied to simultaneously correlate qualitative errors and brain metabolism, collected with FDG-PET.

Metabolic connectivity of resting-state networks in alpha synucleinopathies, from prodromal to dementia phase.

Previous evidence suggests that the derangement of large-scale brain networks reflects structural, molecular, and functional mechanisms underlying neurodegenerative diseases. Although the alterations of multiple large-scale brain networks in Parkinson's disease (PD) and Dementia with Lewy Bodies (DLB) are reported, a comprehensive study on connectivity reconfiguration starting from the preclinical phase is still lacking. We aimed to investigate shared and disease-specific changes in the large-scale networks across the Lewy Bodies (LB) disorders spectrum using a brain metabolic connectivity approach.