Appropriate reference region selection of 18F-florbetaben and 18F-flutemetamol beta-amyloid PET expressed in Centiloid

In Alzheimer’s disease, postmortem studies have shown that the first cortical site where neurofibrillary tangles appear is the transentorhinal region, a subregion within the medial temporal lobe that largely overlaps with area 35, and the entorhinal cortex. Here we used tau-PET imaging to investigate the sequence of tau pathology progression within the human medial temporal lobe and across regions in the posterior-medial system. Our objective was to study how medial temporal tau is related to functional connectivity, regional atrophy, and memory performance. We included 215 β-amyloid negative cognitively unimpaired, 81 β-amyloid positive cognitively unimpaired and 87 β-amyloid positive individuals with mild cognitive impairment, who each underwent [18]F-RO948 tau and [18]F-flutemetamol amyloid PET imaging, structural T1-MRI and memory assessments as part of the Swedish BioFINDER-2 study. First, event-based modelling revealed that the entorhinal cortex and area 35 show the earliest signs of tau accumulation followed by the anterior and posterior hippocampus, area 36 and the parahippocampal cortex. In later stages, tau accumulation became abnormal in neocortical temporal and finally parietal brain regions. Second, in cognitively unimpaired individuals, increased tau load was related to local atrophy in the entorhinal cortex, area 35 and the anterior hippocampus and tau load in several anterior medial temporal lobe subregions was associated with distant atrophy of the posterior hippocampus. Tau load, but not atrophy, in these regions was associated with lower memory performance. Further, tau-related reductions in functional connectivity in critical networks between the medial temporal lobe and regions in the posterior-medial system were associated with this early memory impairment. Finally, in patients with mild cognitive impairment, the association of tau load in the hippocampus with memory performance was partially mediated by posterior hippocampal atrophy. In summary, our findings highlight the progression of tau pathology across medial temporal lobe subregions and its disease-stage specific association with memory performance. While tau pathology might affect memory performance in cognitively unimpaired individuals via reduced functional connectivity in critical medial temporal lobe-cortical networks, memory impairment in mild cognitively impaired patients is associated with posterior hippocampal atrophy.

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“…Amyloid-β PET imaging was performed on the same platform 90–110 min after the injection of ∼185 MBq 18 F-flutemetamol. 20 …”

Section: Methodsmentioning

confidence: 99%

Early stages of tau pathology and its associations with functional connectivity, atrophy and memory

Berron

Vogel

Insel

et al. 2021

Brain

106

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“…Aβ burden was assessed using FBB PET. FBB PET data were expressed as SUVR scaled on a composite reference region including the whole cerebellum [ 35 , 36 ]. VOIs were individually defined in the bilateral frontal, temporal, parietal, and occipital cortices; bilateral posterior cingulate and precuneus; bilateral striatum and thalamus; and brainstem and cerebellar cortex.…”

Section: Methodsmentioning

confidence: 99%

The impact of subthreshold levels of amyloid deposition on conversion to dementia in patients with amyloid-negative amnestic mild cognitive impairment

Kim

Lim

et al. 2022

Alz Res Therapy

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Background About 40–50% of patients with amnestic mild cognitive impairment (MCI) are found to have no significant Alzheimer’s pathology based on amyloid PET positivity. Notably, conversion to dementia in this population is known to occur much less often than in amyloid-positive MCI. However, the relationship between MCI and brain amyloid deposition remains largely unknown. Therefore, we investigated the influence of subthreshold levels of amyloid deposition on conversion to dementia in amnestic MCI patients with negative amyloid PET scans. Methods This study was a retrospective cohort study of patients with amyloid-negative amnestic MCI who visited the memory clinic of Asan Medical Center. All participants underwent detailed neuropsychological testing, brain magnetic resonance imaging, and [18F]-florbetaben (FBB) positron emission tomography scan (PET). Conversion to dementia was determined by a neurologist based on a clinical interview with a detailed neuropsychological test or a decline in the Korean version of the Mini-Mental State Examination score of more than 4 points per year combined with impaired activities of daily living. Regional cortical amyloid levels were calculated, and a receiver operating characteristic (ROC) curve for conversion to dementia was obtained. To increase the reliability of the results of the study, we analyzed the Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset together. Results During the follow-up period, 36% (39/107) of patients converted to dementia from amnestic MCI. The dementia converter group displayed increased standardized uptake value ratio (SUVR) values of FBB on PET in the bilateral temporal, parietal, posterior cingulate, occipital, and left precuneus cortices as well as increased global SUVR. Among volume of interests, the left parietal SUVR predicted conversion to dementia with the highest accuracy in the ROC analysis (area under the curve [AUC] = 0.762, P < 0.001). The combination of precuneus, parietal cortex, and FBB composite SUVRs also showed a higher accuracy in predicting conversion to dementia than other models (AUC = 0.763). Of the results of ADNI data, the SUVR of the left precuneus SUVR showed the highest AUC (AUC = 0.596, P = 0.006). Conclusion Our findings suggest that subthreshold amyloid levels may contribute to conversion to dementia in patients with amyloid-negative amnestic MCI.

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“…Amyloid-b PET imaging was performed on the same platform 90-110 min after the injection of $185 MBq 18 F-flutemetamol. 20…”

Section: Tau and Amyloid-b Petmentioning

confidence: 99%

Early stages of tau pathology and its associations with functional connectivity, atrophy and memory

Berron

Vogel

Insel

et al. 2021

Alzheimer's & Dementia

View full text Add to dashboard Cite

Background: In Alzheimer's disease, postmortem studies have shown that the first cortical site where neurofibrillary tangles appear is the transentorhinal region, a subregion within the medial temporal lobe that largely overlaps with area 35, and the entorhinal cortex. Here we used tau-PET imaging to investigate the sequence of tau pathology progression within the human medial temporal lobe and across regions in the posterior-medial system. Our objective was to study how medial temporal tau is related to functional connectivity, regional atrophy, and memory performance.

show abstract

Appropriate reference region selection of 18F-florbetaben and 18F-flutemetamol beta-amyloid PET expressed in Centiloid

Cited by 34 publications

References 22 publications

Early stages of tau pathology and its associations with functional connectivity, atrophy and memory

Early stages of tau pathology and its associations with functional connectivity, atrophy and memory

The impact of subthreshold levels of amyloid deposition on conversion to dementia in patients with amyloid-negative amnestic mild cognitive impairment

Early stages of tau pathology and its associations with functional connectivity, atrophy and memory

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