The core biomarker pattern is in line with the current pathophysiologic model of AD. Fully normal and fully abnormal pattern is associated with exceptional and universal development of dementia. Cases not in line might be due to atypical neurobiology or inaccurate thresholds for biomarker (ab)normality.
Objectives: The aim of this study was to investigate predictors of progressive cognitive deterioration in patients with suspected non-Alzheimer disease pathology (SNAP) and mild cognitive impairment (MCI). Methods:We measured markers of amyloid pathology (CSF b-amyloid 42) and neurodegeneration (hippocampal volume on MRI and cortical metabolism on [18 F]-fluorodeoxyglucose-PET) in 201 patients with MCI clinically followed for up to 6 years to detect progressive cognitive deterioration. We categorized patients with MCI as A1/A2 and N1/N2 based on presence/absence of amyloid pathology and neurodegeneration. SNAPs were A2N1 cases.Results: The proportion of progressors was 11% (8/41), 34% (14/41), 56% (19/34), and 71%(60/85) in A2N2, A1N2, SNAP, and A1N1, respectively; the proportion of APOE e4 carriers was 29%, 70%, 31%, and 71%, respectively, with the SNAP group featuring a significantly different proportion than both A1N2 and A1N1 groups (p # 0.005). Hypometabolism in SNAP patients was comparable to A1N1 patients (p 5 0.154), while hippocampal atrophy was more severe in SNAP patients (p 5 0.002). Compared with A2N2, SNAP and A1N1 patients had significant risk of progressive cognitive deterioration (hazard ratio 5 2.7 and 3.8, p 5 0.016 and p , 0.001), while A1N2 patients did not (hazard ratio 5 1.13, p 5 0.771). In A1N2 and A1N1 groups, none of the biomarkers predicted time to progression. In the SNAP group, lower time to progression was correlated with greater hypometabolism (r 5 0.42, p 5 0.073). The amyloid cascade hypothesis 1,2 has so far dominated the Alzheimer disease (AD) field. Jack et al. Conclusions:3,4 proposed a dynamic model that relates disease stage to the best established biomarkers of AD pathology. Based on this, a National Institute on Aging-Alzheimer's Association task force developed recommendations for the diagnosis of preclinical AD based on biomarkers of amyloidosis and neuronal injury.5 Soon afterward, these criteria were operationalized and a
Background/aimsAs a protrusion from the brain, the retina might reflect the status of the brain. Previous studies showed a decrease in vessel density and foveal avascular zone (FAZ) enlargement on optical coherence tomography angiography (OCTA) in individuals suffering from Alzheimer’s disease (AD). This study aims to assess whether such changes are already present in preclinical stages of AD, in a population of monozygotic (MZ) twins.Methods124 cognitively healthy individuals (MZ twins, ages 60–93 years) underwent [18F]flutemetamol amyloid positron emission tomography (PET) scanning and OCTA. PET scans were visually rated for cortical amyloid-beta (Aβ) positivity. Parametric global cortical non-displaceable binding potential (BPND) was used as a continuous measure for Aβ aggregation. FAZ size and vessel densities for the inner and outer ring of the macular ETDRS grid and in a 3–6 mm ring around the optic nerve head (ONH) were measured.OCTA measures were associated with visual Aβ score, BPND and amyloid load estimated by twin concordance on visual Aβ score. Twin correlations were estimated as a measure of maximum heritability of OCTA measures.Results13 of 124 participants were Aβ+. Aβ+ individuals had significantly higher vessel density than Aβ– individuals in all regions but did not differ in FAZ size. Twin analyses showed a positive association between and vessel densities in all regions. BPND tended to be associated with higher vessel density in the inner ring. Twin correlations were moderate/high for all OCTA parameters except vessel density around the ONH, which correlated weakly.ConclusionRetinal vessel density was higher in individuals with preclinical AD.
Concordance between CSF Aβ42 and [11C]PIB PET was good in all diagnostic groups. Discordance was mostly seen in MCI and AD patients close to the cut-point. These results provide convergent validity for the use of both types of biomarkers as measures of AD pathology.
The present procedural guidelines summarize the current views of the EANM Neuro-Imaging Committee (NIC). The purpose of these guidelines is to assist nuclear medicine practitioners in making recommendations, performing, interpreting, and reporting results of [18F]FDG-PET imaging of the brain. The aim is to help achieve a high-quality standard of [18F]FDG brain imaging and to further increase the diagnostic impact of this technique in neurological, neurosurgical, and psychiatric practice. The present document replaces a former version of the guidelines that have been published in 2009. These new guidelines include an update in the light of advances in PET technology such as the introduction of digital PET and hybrid PET/MR systems, advances in individual PET semiquantitative analysis, and current broadening clinical indications (e.g., for encephalitis and brain lymphoma). Further insight has also become available about hyperglycemia effects in patients who undergo brain [18F]FDG-PET. Accordingly, the patient preparation procedure has been updated. Finally, most typical brain patterns of metabolic changes are summarized for neurodegenerative diseases. The present guidelines are specifically intended to present information related to the European practice. The information provided should be taken in the context of local conditions and regulations.
The best criteria combined amyloidosis and neurodegeneration biomarkers, whereas the individual biomarker with the best performance was FDG-PET.
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Introduction: Reimbursement of amyloid-positron emission tomography (PET) is lagging due to the lack of definitive evidence on its clinical utility and cost-effectiveness. The Amyloid Imaging to Prevent Alzheimer's Disease-Diagnostic and Patient Management Study (AMYPAD-DPMS) is designed to fill this gap. Methods: AMYPAD-DPMS is a phase 4, multicenter, prospective, randomized controlled study. Nine hundred patients with subjective cognitive decline plus, mild cognitive impairment, and dementia possibly due to Alzheimer's disease will be randomized to ARM1, amyloid-PET performed early in the diagnostic workup; ARM2, amyloid-PET performed after 8 months; and ARM3, amyloid-PET performed whenever the physician chooses to do so. Endpoints: The primary endpoint is the difference between ARM1 and ARM2 in the proportion of patients receiving a very-high-confidence etiologic diagnosis after 3 months. Secondary endpoints address diagnosis and diagnostic confidence, diagnostic/therapeutic management, health economics and patient-related outcomes, and methods for image quantitation.
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