Association of Physical Exercise With Structural Brain Changes and Cognitive Decline in Patients With Early Parkinson Disease.

Background And Objectives: Accumulating evidence suggests that physical activity is associated with a better clinical and cognitive course in Parkinson disease (PD), yet whether these effects are subserved by structural brain alterations are largely unexplored. The aim of this study was to investigate whether regular physical activity associates with a reduced longitudinal rate of neurodegeneration and slower cognitive decline in PD.

Methods: In this longitudinal, observational cohort study, we used data from the Parkinson's Progression Markers Initiative.

Frequency and Clinical Outcomes Associated With Tau Positron Emission Tomography Positivity.

Importance: Tau positron emission tomography (PET) allows in vivo detection of neurofibrillary tangles, a core neuropathologic feature of Alzheimer disease (AD).

Objective: To provide estimates of the frequency of tau PET positivity and its associated risk of clinical outcomes.

Design, Setting, And Participants: Longitudinal study using data pooled from 21 cohorts, comprising a convenience sample of 6514 participants from 13 countries, collected between January 2013 and June 2024.

Data-driven characterization of distinct cognitive subtypes in Parkinson's disease dementia.

Individual cognitive profiles of patients with Parkinson's disease dementia (PDD) are highly heterogeneous, suggesting possible biological subtypes. We studied 75 PD patients who developed dementia in the course of the Parkinson's Progression Markers Initiative study to investigate data-driven evidence for the existence of distinct cognitive subtypes of PDD. Using Ward's hierarchical clustering on neuropsychological test data, we identified two distinct cognitive subtypes.

Hypometabolism and atrophy patterns associated with Niemann-Pick type C.

Background: Niemann-Pick disease type C (NP-C) is a rare genetic lysosomal lipid storage disorder characterized by progressive neurological impairment. Early diagnosis is critical for initiating treatment with miglustat, which can decelerate disease progression. In this study, we evaluated a cohort of 22 NP-C patients who underwent MRI, [F]FDG PET, and clinical assessment at baseline.

The effect of Lewy body (co-)pathology on the clinical and imaging phenotype of amnestic patients.

Lewy body (LB) pathology is present as a co-pathology in ∼50% of patients with Alzheimer's disease (AD) and may even represent the main neuropathologic substrate in a subset of patients with amnestic impairments. However, the degree to which LB pathology affects regional neurodegeneration patterns and clinical trajectories among amnestic patients is not well understood. We studied 865 patients from the Alzheimer's Disease Neuroimaging Initiative cohort with clinical diagnoses of amnestic mild cognitive impairment (n = 661) or AD dementia (n = 211), who had CSF and FDG-PET data available.

Imaging biomarkers of cortical neurodegeneration underlying cognitive impairment in Parkinson's disease.

Purpose: Imaging biomarkers bear great promise for improving the diagnosis and prognosis of cognitive impairment in Parkinson's disease (PD). We compared the ability of three commonly used neuroimaging modalities to detect cortical changes in PD patients with mild cognitive impairment (PD-MCI) and dementia (PDD).

Methods: 53 cognitively normal PD patients (PD-CN), 32 PD-MCI, and 35 PDD underwent concurrent structural MRI (sMRI), diffusion-weighted MRI (dMRI), and [F]FDG PET.

Cortical hypometabolism in Parkinson's disease is linked to cholinergic basal forebrain atrophy.

Cortical hypometabolism on FDG-PET is a well-established neuroimaging biomarker of cognitive impairment in Parkinson's disease (PD), but its pathophysiologic origins are incompletely understood. Cholinergic basal forebrain (cBF) degeneration is a prominent pathological feature of PD-related cognitive impairment and may contribute to cortical hypometabolism through cholinergic denervation of cortical projection areas. Here, we investigated in-vivo associations between subregional cBF volumes on 3T-MRI, cortical hypometabolism on [F]FDG-PET, and cognitive deficits in a cohort of 95 PD participants with varying degrees of cognitive impairment.

Quantitative brain [F]FDG PET beyond normal blood glucose levels.

Introduction SUV measurements from static brain [F]FDG PET acquisitions are a commonly used tool in preclinical research, providing a simple alternative for kinetic modelling, which requires complex and time-consuming dynamic acquisitions. However, SUV can be severely affected by the animal handling and preconditioning protocols, primarily by those that may induce changes in blood glucose levels (BGL). Here, we aimed at developing and investigating the feasibility of SUV-based approaches for a wide range of BGL far beyond normal values, and consequently, to develop and validate a new model to generate standardized and reproducible SUV measurements for any BGL.

Partial volume correction in longitudinal tau PET studies: is it really needed?

Background: [F]flortaucipir (FTP) tau PET quantification is known to be affected by non-specific binding in off-target regions. Although partial volume correction (PVC) techniques partially account for this effect, their inclusion may also introduce noise and variability into the quantification process. While the impact of these effects has been studied in cross-sectional designs, the benefits and drawbacks of PVC on longitudinal FTP studies is still under scrutiny.

Increased Medial Temporal Tau Positron Emission Tomography Uptake in the Absence of Amyloid-β Positivity.

Importance: An increased tau positron emission tomography (PET) signal in the medial temporal lobe (MTL) has been observed in older individuals in the absence of amyloid-β (Aβ) pathology. Little is known about the longitudinal course of this condition, and its association with Alzheimer disease (AD) remains unclear.

Objective: To study the pathologic and clinical course of older individuals with PET-evidenced MTL tau deposition (TMTL+) in the absence of Aβ pathology (A-), and the association of this condition with the AD continuum.

Basal Forebrain Atrophy, Cortical Thinning, and Amyloid-β Status in Parkinson's disease-Related Cognitive Decline.

Background: Degeneration of the cortically-projecting cholinergic basal forebrain (cBF) is a well-established pathologic correlate of cognitive decline in Parkinson's disease (PD). In Alzheimer's disease (AD) the effect of cBF degeneration on cognitive decline was found to be mediated by parallel atrophy of denervated cortical areas.

Objectives: To examine whether the association between cBF degeneration and cognitive decline in PD is mediated by parallel atrophy of cortical areas and whether these associations depend on the presence of comorbid AD pathology.

Characteristics of amnestic patients with hypometabolism patterns suggestive of Lewy body pathology.

A clinical diagnosis of Alzheimer's disease dementia (ADD) encompasses considerable pathological and clinical heterogeneity. While Alzheimer's disease patients typically show a characteristic temporo-parietal pattern of glucose hypometabolism on 18F-fluorodeoxyglucose (FDG)-PET imaging, previous studies have identified a subset of patients showing a distinct posterior-occipital hypometabolism pattern associated with Lewy body pathology. Here, we aimed to improve the understanding of the clinical relevance of these posterior-occipital FDG-PET patterns in patients with Alzheimer's disease-like amnestic presentations.

Peripheral Inflammation Is Associated with Dopaminergic Degeneration in Parkinson's Disease.

Background: Peripheral inflammatory immune responses are suggested to play a major role in dopaminergic degeneration in Parkinson's disease (PD). The neutrophil-to-lymphocyte ratio (NLR) is a well-established biomarker of systemic inflammation in PD. Degeneration of the nigrostriatal dopaminergic system can be assessed in vivo using [ I]FP-CIT single photon emission computed tomography imaging of striatal dopamine transporter (DAT) density.

Differential Effects of Tau Stage, Lewy Body Pathology, and Substantia Nigra Degeneration on F-FDG PET Patterns in Clinical Alzheimer Disease.

Comorbid Lewy body (LB) pathology is common in Alzheimer disease (AD). The effect of LB copathology on F-FDG PET patterns in AD is yet to be studied. We analyzed associations of neuropathologically assessed tau pathology, LB pathology, and substantia nigra neuronal loss (SNnl) with antemortem F-FDG PET hypometabolism in patients with a clinical AD presentation.

Differential diagnosis of amnestic dementia patients based on an FDG-PET signature of autopsy-confirmed LATE-NC.

Introduction: Limbic age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) is common in advanced age and can underlie a clinical presentation mimicking Alzheimer's disease (AD). We studied whether an autopsy-derived fluorodeoxyglucose positron emission tomography (FDG-PET) signature of LATE-NC provides clinical utility for differential diagnosis of amnestic dementia patients.

Methods: Ante mortem FDG-PET patterns from autopsy-confirmed LATE-NC (N = 7) and AD (N = 23) patients were used to stratify an independent cohort of clinically diagnosed AD dementia patients (N = 242) based on individual FDG-PET profiles.

Impact of spill-in counts from off-target regions on [F]Flortaucipir PET quantification.

Background: [F]Flortaucipir (FTP) PET quantification is usually hindered by spill-in counts from off-target binding (OFF) regions. The present work aims to provide an in-depth analysis of the impact of OFF in FTP PET quantification, as well as to identify optimal partial volume correction (PVC) strategies to minimize this problem.

Methods: 309 amyloid-beta (Aβ) negative cognitively normal subjects were included in the study.

F-florbetapir PET as a marker of myelin integrity across the Alzheimer's disease spectrum.

Purpose: Recent evidence suggests that PET imaging with amyloid-β (Aβ) tracers can be used to assess myelin integrity in cerebral white matter (WM). Alzheimer's disease (AD) is characterized by myelin changes that are believed to occur early in the disease course. Nevertheless, the extent to which demyelination, as measured with Aβ PET, contributes to AD progression remains unexplored.

SimPET-An open online platform for the Monte Carlo simulation of realistic brain PET data. Validation for F-FDG scans.

Purpose: SimPET (www.sim-pet.org) is a free cloud-based platform for the generation of realistic brain positron emission tomography (PET) data.

A Systematic Review of PET Textural Analysis and Radiomics in Cancer.

Background: Although many works have supported the utility of PET radiomics, several authors have raised concerns over the robustness and replicability of the results. This study aimed to perform a systematic review on the topic of PET radiomics and the used methodologies.

Methods: PubMed was searched up to 15 October 2020.

Is FDG-PET texture analysis related to intratumor biological heterogeneity in lung cancer?

Objectives: We aimed at investigating the origin of the correlations between tumor volume and F-FDG-PET texture indices in lung cancer.

Methods: Eighty-five consecutive patients with newly diagnosed non-small cell lung cancer (NSCLC) underwent a F-FDG-PET/CT scan before treatment. Seven phantom spheres uniformly filled with F-FDG, and covering a range of activities and volumes similar to that found in lung tumors, were also scanned.

Feasibility of Longitudinal Brain PET with Real-Time Arterial Input Function in Rats.

Purpose: Preclinical dynamic brain PET studies remain hampered by the limitations related to the measurement of the arterial input function (AIF). In this regard, the use of an arterial-venous shunt is a promising method for the generation of real-time AIFs, but its application in longitudinal studies is still impeded by the cumbersome surgeries and high failure rates. We studied the feasibility and reproducibility of double arterial-venous shunt strategies for conducting longitudinal PET studies with real-time AIFs in rats.

Intensity normalization methods in brain FDG-PET quantification.

Background: The lack of standardization of intensity normalization methods and its unknown effect on the quantification output is recognized as a major drawback for the harmonization of brain FDG-PET quantification protocols. The aim of this work is the ground truth-based evaluation of different intensity normalization methods on brain FDG-PET quantification output.

Methods: Realistic FDG-PET images were generated using Monte Carlo simulation from activity and attenuation maps directly derived from 25 healthy subjects (adding theoretical relative hypometabolisms on 6 regions of interest and for 5 hypometabolism levels).

White matter hyperintensities are associated with subthreshold amyloid accumulation.

The association between white matter hyperintensities (WMH) and amyloid accumulation over time in cognitively normal, amyloid-negative elderly people remains largely unexplored. In order to study whether baseline WMH were associated with longitudinal subthreshold amyloid accumulation, 159 cognitively normal participants from the Alzheimer's Disease Neuroimaging Initiative who were amyloid-negative at baseline were examined. All the participants underwent a T1 and a Fluid-Attenuated Inversion Recovery MRI scan at baseline.