Amyloid PET disclosure in subjective cognitive decline: Patient experiences over time.

Introduction: We disclosed amyloid positron emission tomography (PET) results in individuals with subjective cognitive decline (SCD) and studied patient experiences and outcomes over a 6-month period.

Methods: Fifty-seven participants from the Subjective Cognitive Impairment Cohort (SCIENCe) (66 ± 8 years, 21 [37%] F, Mini-Mental State Examination 29 ± 1, 15 [26%] amyloid positive [A+]) completed questionnaires 1 week prior (T0), 1 day after (T1), and 6 months after amyloid PET disclosure (T2). Questionnaires addressed patient-reported experiences and outcomes.

Neuropsychological functioning after COVID-19: minor differences between individuals with and without persistent complaints after SARS-CoV-2 infection.

It is unclear how self-reported severe fatigue and difficulty concentrating after SARS-CoV-2 infection relate to objective neuropsychological functioning. The study aimed to compare neuropsychological functioning between individuals with and without these persistent subjective complaints. : Individuals with and without persistent severe fatigue (Checklist Individual Strength (CIS) fatigue ≥ 35) and difficulty concentrating (CIS concentration ≥ 18) at least 3 months after SARS-CoV-2 infection were included.

Validation of image-derived input function using a long axial field of view PET/CT scanner for two different tracers.

Background: Accurate image-derived input function (IDIF) from highly sensitive large axial field of view (LAFOV) PET/CT scanners could avoid the need of invasive blood sampling for kinetic modelling. The aim is to validate the use of IDIF for two kinds of tracers, 3 different IDIF locations and 9 different reconstruction settings.

Methods: Eight [F]FDG and 10 [F]DPA-714 scans were acquired respectively during 70 and 60 min on the Vision Quadra PET/CT system.

Head-to-head comparison of relative cerebral blood flow derived from dynamic [F]florbetapir and [F]flortaucipir PET in subjects with subjective cognitive decline.

Background: Dynamic PET imaging studies provide accurate estimates of specific binding, but also measure the relative tracer delivery (R), which is a proxy for relative cerebral blood flow (rCBF). Recently, studies suggested that R obtained from different tracers could be used interchangeably and is irrespective of target tissue. However, the similarities or differences of R obtained from different PET tracers still require validation.

Performance of a [F]Flortaucipir PET Visual Read Method Across the Alzheimer Disease Continuum and in Dementia With Lewy Bodies.

Background And Objectives: Recently, the US Food and Drug Administration approved the tau-binding radiotracer [F]flortaucipir and an accompanying visual read method to support the diagnostic process in cognitively impaired patients assessed for Alzheimer disease (AD). Studies evaluating this visual read method are limited. In this study, we evaluated the performance of the visual read method in participants along the AD continuum and dementia with Lewy bodies (DLB) by determining its reliability, accordance with semiquantitative analyses, and associations with clinically relevant variables.

Neurobiological basis and risk factors of persistent fatigue and concentration problems after COVID-19: study protocol for a prospective case-control study (VeCosCO).

Introduction: The risk factors for persistent fatigue and cognitive complaints after infection with SARS-CoV-2 and the underlying pathophysiology are largely unknown. Both clinical factors and cognitive-behavioural factors have been suggested to play a role in the perpetuation of complaints. A neurobiological aetiology, such as neuroinflammation, could be the underlying pathophysiological mechanism for persisting complaints.

Tau protein spreads through functionally connected neurons in Alzheimer's disease: a combined MEG/PET study.

Recent studies on Alzheimer's disease (AD) suggest that tau proteins spread through the brain following neuronal connections. Several mechanisms could be involved in this process: spreading between brain regions that interact strongly (functional connectivity); through the pattern of anatomical connections (structural connectivity); or simple diffusion. Using magnetoencephalography (MEG), we investigated which spreading pathways influence tau protein spreading by modelling the tau propagation process using an epidemic spreading model.

Tau pathology as determinant of changes in atrophy and cerebral blood flow: a multi-modal longitudinal imaging study.

Purpose: Tau pathology is associated with concurrent atrophy and decreased cerebral blood flow (CBF) in Alzheimer's disease (AD), but less is known about their temporal relationships. Our aim was therefore to investigate the association of concurrent and longitudinal tau PET with longitudinal changes in atrophy and relative CBF.

Methods: We included 61 individuals from the Amsterdam Dementia Cohort (mean age 65.

Amyloid and tau PET-positive cognitively unimpaired individuals are at high risk for future cognitive decline.

A major unanswered question in the dementia field is whether cognitively unimpaired individuals who harbor both Alzheimer's disease neuropathological hallmarks (that is, amyloid-β plaques and tau neurofibrillary tangles) can preserve their cognition over time or are destined to decline. In this large multicenter amyloid and tau positron emission tomography (PET) study (n = 1,325), we examined the risk for future progression to mild cognitive impairment and the rate of cognitive decline over time among cognitively unimpaired individuals who were amyloid PET-positive (A) and tau PET-positive (T) in the medial temporal lobe (AT) and/or in the temporal neocortex (AT) and compared them with AT and AT groups. Cox proportional-hazards models showed a substantially increased risk for progression to mild cognitive impairment in the AT (hazard ratio (HR) = 19.

Precision estimates of relative and absolute cerebral blood flow in Alzheimer's disease and cognitively normal individuals.

Alzheimer's disease is characterized by regional reductions in cerebral blood flow (CBF). Although the gold standard for measuring CBF is [O]HO PET, proxies of relative CBF, derived from the early distribution phase of amyloid and tau tracers, have gained attention. The present study assessed precision of [O]HO derived relative and absolute CBF, and compared precision of these measures with that of (relative) CBF proxies.

Longitudinal Tau PET Using F-Flortaucipir: The Effect of Relative Cerebral Blood Flow on Quantitative and Semiquantitative Parameters.

Semiquantitative PET measures such as SUV ratio (SUVr) have several advantages over quantitative measures, such as practical applicability and relative computational simplicity. However, SUVr may potentially be affected by changes in blood flow, whereas quantitative measures such as nondisplaceable binding potential (BP) are not. For F-flortaucipir PET, the sensitivity of SUVr for changes in blood flow is currently unknown.

A Head-to-Head Comparison Between Plasma pTau181 and Tau PET Along the Alzheimer's Disease Continuum.

Both plasma tau phosphorylated at threonine-181 (pTau181) and tau PET show potential for detecting Alzheimer's disease (AD) pathology and predicting clinical progression. In this study, we performed a head-to-head comparison between plasma pTau181 and tau PET along the AD continuum. We included participants from the Amsterdam Dementia Cohort who underwent F-flortaucipir (tau) PET and had a plasma sample biobanked within 12 mo from tau PET.

Cerebral blood flow, amyloid burden, and cognition in cognitively normal individuals.

Purpose: The role of cerebral blood flow (CBF) in the early stages of Alzheimer's disease is complex and largely unknown. We investigated cross-sectional and longitudinal associations between CBF, amyloid burden, and cognition, in cognitively normal individuals with subjective cognitive decline (SCD).

Methods: We included 187 cognitively normal individuals with SCD from the SCIENCe project (65 ± 8 years, 39% F, MMSE 29 ± 1).

Longitudinal change in ATN biomarkers in cognitively normal individuals.

Background: Biomarkers for amyloid, tau, and neurodegeneration (ATN) have predictive value for clinical progression, but it is not clear how individuals move through these stages. We examined changes in ATN profiles over time, and investigated determinants of change in A status, in a sample of cognitively normal individuals presenting with subjective cognitive decline (SCD).

Methods: We included 92 individuals with SCD from the SCIENCe project with [F]florbetapir PET (A) available at two time points (65 ± 8y, 42% female, MMSE 29 ± 1, follow-up 2.

Differential associations between neocortical tau pathology and blood flow with cognitive deficits in early-onset vs late-onset Alzheimer's disease.

Purpose: Early-onset Alzheimer's disease (EOAD) and late-onset Alzheimer's disease (LOAD) differ in neuropathological burden and type of cognitive deficits. Assessing tau pathology and relative cerebral blood flow (rCBF) measured with [F]flortaucipir PET in relation to cognition may help explain these differences between EOAD and LOAD.

Methods: Seventy-nine amyloid-positive individuals with a clinical diagnosis of AD (EOAD: n = 35, age-at-PET = 59 ± 5, MMSE = 23 ± 4; LOAD: n = 44, age-at-PET = 71 ± 5, MMSE = 23 ± 4) underwent a 130-min dynamic [F]flortaucipir PET scan and extensive neuropsychological assessment.

[F]Flortaucipir PET Across Various Mutations in Presymptomatic and Symptomatic Carriers.

Objective: To assess the [F]flortaucipir binding distribution across mutations in presymptomatic and symptomatic carriers.

Methods: We compared regional [F]flortaucipir binding potential (BP) derived from a 130-minute dynamic [F]flortaucipir PET scan in 9 (pre)symptomatic mutation carriers (4 with P301L [1 symptomatic], 2 with R406W [1 symptomatic], 1 presymptomatic L315R, 1 presymptomatic S320F, and 1 symptomatic G272V carrier) with 30 cognitively normal controls and 52 patients with Alzheimer disease.

Results: [F]Flortaucipir BP images showed overall highest binding in the symptomatic carriers.

Heterogeneous distribution of tau pathology in the behavioural variant of Alzheimer's disease.

Objective: The clinical phenotype of the rare behavioural variant of Alzheimer's disease (bvAD) is insufficiently understood. Given the strong clinico-anatomical correlations of tau pathology in AD, we investigated the distribution of tau deposits in bvAD, in-vivo and ex-vivo, using positron emission tomography (PET) and postmortem examination.

Methods: For the tau PET study, seven amyloid-β positive bvAD patients underwent [F]flortaucipir or [F]RO948 PET.

Effect of Shortening the Scan Duration on Quantitative Accuracy of [F]Flortaucipir Studies.

Purpose: Dynamic positron emission tomography (PET) protocols allow for accurate quantification of [F]flortaucipir-specific binding. However, dynamic acquisitions can be challenging given the long required scan duration of 130 min. The current study assessed the effect of shorter scan protocols for [F]flortaucipir on its quantitative accuracy.

Isocaloric low protein diet in a mouse model for vanishing white matter does not impact ISR deregulation in brain, but reveals ISR deregulation in liver.

Vanishing white matter (VWM) is a genetic brain white matter disorder caused by mutations in eIF2B. eIF2B is central in the integrated stress response (ISR), during which its activity is inhibited by various cellular stresses. VWM is a chronic progressive disease with episodes of rapid neurological deterioration provoked by stresses.

Tau pathology and relative cerebral blood flow are independently associated with cognition in Alzheimer's disease.

Purpose: We aimed to investigate associations between tau pathology and relative cerebral blood flow (rCBF), and their relationship with cognition in Alzheimer's disease (AD), by using a single dynamic [F]flortaucipir positron emission tomography (PET) scan.

Methods: Seventy-one subjects with AD (66 ± 8 years, mini-mental state examination (MMSE) 23 ± 4) underwent a dynamic 130-min [F]flortaucipir PET scan. Cognitive assessment consisted of composite scores of four cognitive domains.

Correction to: Regional [F]flortaucipir PET is more closely associated with disease severity than CSF p-tau in Alzheimer's disease.

The authors regret to inform readers that the following error was detected in the original article. The values for entorhinal, limbic and neortical SUVr were switched between SCD Aβ + and Aβ- in Table 1 and have now been corrected. Unnecessary symbols in Table 2 have been removed.

Regional [F]flortaucipir PET is more closely associated with disease severity than CSF p-tau in Alzheimer's disease.

Purpose: In vivo Alzheimer's disease (AD) biomarkers for tau pathology are cerebrospinal fluid (CSF) phosphorylated tau (p-tau) and [F]flortaucipir positron emission tomography (PET). Our aim was to assess associations between CSF p-tau with [F]flortaucipir PET and the associations of both tau biomarkers with cognition and atrophy.

Methods: We included 78 amyloid positive cognitively impaired patients (clinical diagnoses mild cognitive impairment (MCI, n = 8) and AD dementia (n = 45) and 25 cognitively normal subjects with subjective cognitive decline (SCD) (40% amyloid-positive)).

Hippocampal [F]flortaucipir BP corrected for possible spill-in of the choroid plexus retains strong clinico-pathological relationships.

Background: Off-target [F]flortaucipir (tau) PET binding in the choroid plexus causes spill-in into the nearby hippocampus, which may influence the correlation between [F]flortaucipir binding and measures of cognition. Previously, we showed that partial volume correction (combination of Van Cittert iterative deconvolution and HYPR denoising; PVC HDH) and manually eroding the hippocampus resulted in a significant decrease of the choroid plexus spill-in. In this study, we compared three different approaches for the quantification of hippocampal [F]flortaucipir signal using a semi-automated technique, and assessed correlations with cognitive performance across methods.

Test-retest repeatability of [F]Flortaucipir PET in Alzheimer's disease and cognitively normal individuals.

The aim of this study was to investigate the test-retest (TRT) repeatability of various parametric quantification methods for [F]Flortaucipir positron emission tomography (PET). We included eight subjects with dementia or mild cognitive impairment due to Alzheimer's disease and six cognitively normal subjects. All underwent two 130-min dynamic [F]Flortaucipir PET scans within 3 ± 1 weeks.

Associations between quantitative [F]flortaucipir tau PET and atrophy across the Alzheimer's disease spectrum.

Background: Neuropathological studies have linked tau aggregates to neuronal loss. To describe the spatial distribution of neurofibrillary tangle pathology in post-mortem tissue, Braak staging has been used. The aim of this study was to examine in vivo associations between tau pathology, quantified with [F]flortaucipir PET in regions corresponding to Braak stages, and atrophy across the Alzheimer's disease (AD) spectrum.