| 1. |
- Collij, Lyduine E., et al.
(författare)
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Quantification of [18F]florbetaben amyloid-PET imaging in a mixed memory clinic population : The ABIDE project
- 2023
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Ingår i: Alzheimer's and Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 19:6, s. 2397-2407
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: We investigated amyloid-burden quantification in a mixed memory clinic population. Methods: [18F]Florbetaben amyloid-PET (positron emission tomography) scans of 348 patients were visually read and quantified using the Centiloid (CL) method. General linear models were used to assess CL differences across syndromic and etiological diagnosis. Linear mixed models were fitted to assess the predictive value of visual read (VR) and CL on longitudinal Mini-Mental Status Examination (MMSE). Results: CL was associated with syndromic (F = 4.42, p = 0.014) and etiological diagnosis (F = -12.66, p < 0.001), with Alzheimer's disease (AD) patients showing the highest amyloid burden (62.9 ± 27.5), followed by dementia with Lewy bodies (DLB) (25.3 ± 35.5) and cardiovascular disease (CVD) (16.7 ± 24.5), and finally frontotemporal lobe degeneration (FTLD) (5.0 ± 17.22, t = –12.66, p < 0.001). CL remained predictive of etiological diagnosis (t = –2.41, p = 0.017) within the VR+ population (N = 157). VR was not a significant predictor of MMSE (t = –1.53, p = 0.13) for the SCD population (N = 90), whereas CL was (t = -3.30, p = 0.001). Discussion: The extent of amyloid pathology through quantification holds clinical value, potentially in the context of differential diagnosis as well as prognosis.
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| 2. |
- Leijenaar, Jolien F., et al.
(författare)
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Comorbid amyloid-β pathology affects clinical and imaging features in VCD
- 2020
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Ingår i: Alzheimer's and Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 16:2, s. 354-364
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: To date, the clinical relevance of comorbid amyloid-β (Aβ) pathology in patients with vascular cognitive disorders (VCD) is largely unknown. Methods: We included 218 VCD patients with available cerebrospinal fluid Aβ42 levels. Patients were divided into Aβ+ mild-VCD (n = 84), Aβ− mild-VCD (n = 68), Aβ+ major-VCD (n = 31), and Aβ− major-VCD (n = 35). We measured depression with the Geriatric Depression Scale, cognition with a neuropsychological test battery and derived white matter hyperintensities (WMH) and gray matter atrophy from MRI. Results: Aβ− patients showed more depressive symptoms than Aβ+. In the major-VCD group, Aβ− patients performed worse on attention (P =.02) and executive functioning (P =.008) than Aβ+. We found no cognitive differences in patients with mild VCD. In the mild-VCD group, Aβ− patients had more WMH than Aβ+ patients, whereas conversely, in the major-VCD group, Aβ+ patients had more WMH. Atrophy patterns did not differ between Aβ+ and Aβ− VCD group. Discussion: Comorbid Aβ pathology affects the manifestation of VCD, but effects differ by severity of VCD.
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| 3. |
- Salvadó, Gemma, et al.
(författare)
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The protective gene dose effect of the APOE ε2 allele on gray matter volume in cognitively unimpaired individuals
- 2022
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Ingår i: Alzheimer's and Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 18:7, s. 1383-1395
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Harboring two copies of the apolipoprotein E (APOE) ε2 allele strongly protects against Alzheimer's disease (AD). However, the effect of this genotype on gray matter (GM) volume in cognitively unimpaired individuals has not yet been described. Methods: Multicenter brain magnetic resonance images (MRIs) from cognitively unimpaired ε2 homozygotes were matched (1:1) against all other APOE genotypes for relevant confounders (n = 223). GM volumes of ε2 genotypic groups were compared to each other and to the reference group (APOE ε3/ε3). Results: Carrying at least one ε2 allele was associated with larger GM volumes in brain areas typically affected by AD and also in areas associated with cognitive resilience. APOE ε2 homozygotes, but not APOE ε2 heterozygotes, showed larger GM volumes in areas related to successful aging. Discussion: In addition to the known resistance against amyloid-β deposition, the larger GM volumes in key brain regions may confer APOE ε2 homozygotes additional protection against AD-related cognitive decline.
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| 4. |
- Wink, Alle Meije, et al.
(författare)
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Quantifying AD-related brain amyloid with linearised progression models : model-based vs. data-based.
- 2022
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Ingår i: Alzheimer's and Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 18:S1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Brain amyloid-β (Aβ) is the pathological hallmark of Alzheimer's disease (AD). In logistic disease models, Aβ accumulation is a sigmoid function of time-since-disease-onset (TSDO) (figure 1). Previous positron emission tomography (PET)-based models vary accumulation onset(t50) and duration(r) globally; capacity(K) and baseline(NS) regionally (Whittington2018). We confirm existing approaches and propose a more powerful ICA-based approach to quantify disease severity and estimate TSDO. Method: We used 1071 18F-florbetapir standard uptake value ratio (SUVR) images from the ADNI-2 study (adni.loni.usc.edu/data-samples/data-types/pet). Images were mapped into MNI space. Averages were extracted using the Harvard-Oxford brain-atlas. Whole-brain tracer-specific sigmoid parameters (Jack2013) obtained from the literature were used to estimate TSDO. Of 16 models of regional Aβ accumulation (each of the 4 regional sigmoid parameters varied either regionally or globally), the optimal Bayesian information criterion was found with global t50 and r, and regional NS and K (figure 1) with global values r=6.16y and t50=4.10y. Linearised maps of NS and K were obtained by regressing the SUVR maps onto the global sigmoid. We also estimated these maps as independent components, using a 2-component ICA on the SUVR maps. Both outcomes were used to quantify Aβ accumulation from SUVR images as weighting factors of the accumulation map. We compared the weights from the logistic model and the ICA model in ADNI, using effect size measured with Hedges' g between cognitively normal (CN), subjective memory complaints (SMC), mild cognitive impairment (EMCI/MCI/LMCI) and AD groups. We compared 3 longitudinal visits (N=112) in the OASIS-3 study (see www.oasis-brains.org) with both methods, global SUVR and Centiloid (Klunk2015) using 11C-PiB PET SUVR images. Result: Maps of accumulation capacity from both models had spatial correlation of 0.86 (figure 2); baseline maps had spatial correlation of 0.95. Hedges' g between ADNI groups was 2.25 for K, and 2.42 for ICA (1.46 for global SUVR). In OASIS-3, Hedges' g between visits was 1.24 for K, 1.46 for ICA (global SUVR 0.15, Centiloid 0.4). Conclusion: We demonstrate that linear accumulation models can be used to quantify brain Aβ with PET; maps obtained by ICA yield larger effect sizes than the logistic method for differentiating groups and measuring changes between visits.
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| 5. |
- Bollack, Ariane, et al.
(författare)
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Investigating reliable amyloid accumulation in Centiloids : Results from the AMYPAD Prognostic and Natural History Study
- 2024
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Ingår i: Alzheimer's and Dementia. - 1552-5260.
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: To support clinical trial designs focused on early interventions, our study determined reliable early amyloid-β (Aβ) accumulation based on Centiloids (CL) in pre-dementia populations. METHODS: A total of 1032 participants from the Amyloid Imaging to Prevent Alzheimer's Disease–Prognostic and Natural History Study (AMYPAD-PNHS) and Insight46 who underwent [18F]flutemetamol, [18F]florbetaben or [18F]florbetapir amyloid-PET were included. A normative strategy was used to define reliable accumulation by estimating the 95th percentile of longitudinal measurements in sub-populations (NPNHS = 101/750, NInsight46 = 35/382) expected to remain stable over time. The baseline CL threshold that optimally predicts future accumulation was investigated using precision-recall analyses. Accumulation rates were examined using linear mixed-effect models. RESULTS: Reliable accumulation in the PNHS was estimated to occur at >3.0 CL/year. Baseline CL of 16 [12,19] best predicted future Aβ-accumulators. Rates of amyloid accumulation were tracer-independent, lower for APOE ε4 non-carriers, and for subjects with higher levels of education. DISCUSSION: Our results support a 12–20 CL window for inclusion into early secondary prevention studies. Reliable accumulation definition warrants further investigations.
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| 6. |
- Bollack, Ariane, et al.
(författare)
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Longitudinal amyloid and tau PET imaging in Alzheimer's disease : A systematic review of methodologies and factors affecting quantification
- 2023
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Ingår i: Alzheimer's and Dementia. - 1552-5260. ; 19:11, s. 5232-5252
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Forskningsöversikt (refereegranskat)abstract
- Deposition of amyloid and tau pathology can be quantified in vivo using positron emission tomography (PET). Accurate longitudinal measurements of accumulation from these images are critical for characterizing the start and spread of the disease. However, these measurements are challenging; precision and accuracy can be affected substantially by various sources of errors and variability. This review, supported by a systematic search of the literature, summarizes the current design and methodologies of longitudinal PET studies. Intrinsic, biological causes of variability of the Alzheimer's disease (AD) protein load over time are then detailed. Technical factors contributing to longitudinal PET measurement uncertainty are highlighted, followed by suggestions for mitigating these factors, including possible techniques that leverage shared information between serial scans. Controlling for intrinsic variability and reducing measurement uncertainty in longitudinal PET pipelines will provide more accurate and precise markers of disease evolution, improve clinical trial design, and aid therapy response monitoring.
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| 7. |
- de Wilde, Arno, et al.
(författare)
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Assessment of the appropriate use criteria for amyloid PET in an unselected memory clinic cohort : The ABIDE project
- 2019
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Ingår i: Alzheimer's and Dementia. - : Wiley. - 1552-5260.
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The objective of this study was to assess the usefulness of the appropriate use criteria (AUC) for amyloid imaging in an unselected cohort. Methods: We calculated sensitivity and specificity of appropriate use (increased confidence and management change), as defined by Amyloid Imaging Taskforce in the AUC, and other clinical utility outcomes. Furthermore, we compared differences in post–positron emission tomography diagnosis and management change between “AUC-consistent” and “AUC-inconsistent” patients. Results: Almost half (250/507) of patients were AUC-consistent. In both AUC-consistent and AUC-inconsistent patients, post–positron emission tomography diagnosis (28%–21%) and management (32%–17%) change was substantial. The Amyloid Imaging Taskforce's definition of appropriate use occurred in 55/507 (13%) patients, detected by the AUC with a sensitivity of 93%, and a specificity of 56%. Diagnostic changes occurred independently of AUC status (sensitivity: 57%, specificity: 53%). Discussion: The current AUC are not sufficiently able to discriminate between patients who will benefit from amyloid positron emission tomography and those who will not.
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