23 research outputs found
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Florbetapir F 18 amyloid PET and 36-month cognitive decline:a prospective multicenter study
This study was designed to evaluate whether subjects with amyloid beta (Aβ) pathology, detected using florbetapir positron emission tomorgraphy (PET), demonstrated greater cognitive decline than subjects without Aβ pathology. Sixty-nine cognitively normal (CN) controls, 52 with recently diagnosed mild cognitive impairment (MCI) and 31 with probable Alzheimer's disease (AD) dementia were included in the study. PET images obtained in these subjects were visually rated as positive (Aβ+) or negative (Aβ−), blind to diagnosis. Fourteen percent (10/69) of CN, 37% (19/52) of MCI and 68% (21/31) of AD were Aβ+. The primary outcome was change in ADAS-Cog score in MCI subjects after 36 months; however, additional outcomes included change on measures of cognition, function and diagnostic status. Aβ+ MCI subjects demonstrated greater worsening compared with Aβ− subjects on the ADAS-Cog over 36 months (5.66±1.47 vs −0.71±1.09, P=0.0014) as well as on the mini-mental state exam (MMSE), digit symbol substitution (DSS) test, and a verbal fluency test (P<0.05). Similar to MCI subjects, Aβ+ CN subjects showed greater decline on the ADAS-Cog, digit-symbol-substitution test and verbal fluency (P<0.05), whereas Aβ+ AD patients showed greater declines in verbal fluency and the MMSE (P<0.05). Aβ+ subjects in all diagnostic groups also showed greater decline on the CDR-SB (P<0.04), a global clinical assessment. Aβ+ subjects did not show significantly greater declines on the ADCS-ADL or Wechsler Memory Scale. Overall, these findings suggest that in CN, MCI and AD subjects, florbetapir PET Aβ+ subjects show greater cognitive and global deterioration over a 3-year follow-up than Aβ− subjects do
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Early role of vascular dysregulation on late-onset Alzheimer's disease based on multifactorial data-driven analysis
Multifactorial mechanisms underlying late-onset Alzheimer's disease (LOAD) are poorly characterized from an integrative perspective. Here spatiotemporal alterations in brain amyloid-β deposition, metabolism, vascular, functional activity at rest, structural properties, cognitive integrity and peripheral proteins levels are characterized in relation to LOAD progression. We analyse over 7,700 brain images and tens of plasma and cerebrospinal fluid biomarkers from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Through a multifactorial data-driven analysis, we obtain dynamic LOAD–abnormality indices for all biomarkers, and a tentative temporal ordering of disease progression. Imaging results suggest that intra-brain vascular dysregulation is an early pathological event during disease development. Cognitive decline is noticeable from initial LOAD stages, suggesting early memory deficit associated with the primary disease factors. High abnormality levels are also observed for specific proteins associated with the vascular system's integrity. Although still subjected to the sensitivity of the algorithms and biomarkers employed, our results might contribute to the development of preventive therapeutic interventions
Effectiveness of Florbetapir PET Imaging in Changing Patient Management
Aims: To evaluate the impact of amyloid PET imaging on diagnosis and patient management in a multicenter, randomized, controlled study. Methods: Physicians identified patients seeking a diagnosis for mild cognitive impairment or dementia, possibly due to Alzheimer disease (AD), and recorded a working diagnosis and a management plan. The patients underwent florbetapir PET scanning and were randomized to either immediate or delayed (1-year) feedback regarding amyloid status. At the 3-month visit, the physician updated the diagnosis and recorded a summary of the actual patient management since the post-scan visit. The study examined the impact of immediate versus delayed feedback on patient diagnosis/management at 3 and 12 months. Results: A total of 618 subjects were randomized (1:1) to immediate or delayed feedback arms, and 602 subjects completed the 3-month primary endpoint visit. A higher proportion of patients in the immediate feedback arm showed a change in diagnosis compared to the controls (32.6 vs. 6.4%; p = 0.0001). Similarly, a higher proportion of patients receiving immediate feedback had a change in management plan (68 vs. 55.5%; p < 0.002), mainly driven by changes in AD medication. Specifically, acetylcholinesterase inhibitors were prescribed to 67% of the amyloid-positive and 27% of the amyloid-negative subjects in the information group compared with 56 and 43%, respectively, in the control group (p < 0.0001). These between-group differences persisted until the 12-month visit. Conclusion: Knowledge of the amyloid status affects the diagnosis and alters patient management
Brain Blood Flow Related to Acoustic Laryngeal Reaction Time in Adult Developmental Stutterers
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18 F-flortaucipir tau positron emission tomography distinguishes established progressive supranuclear palsy from controls and Parkinson disease: A multicenter study.
Objective18 F-flortaucipir (formerly 18 F-AV1451 or 18 F-T807) binds to neurofibrillary tangles in Alzheimer disease, but tissue studies assessing binding to tau aggregates in progressive supranuclear palsy (PSP) have yielded mixed results. We compared in vivo 18 F-flortaucipir uptake in patients meeting clinical research criteria for PSP (n = 33) to normal controls (n = 46) and patients meeting criteria for Parkinson disease (PD; n = 26).MethodsParticipants underwent magnetic resonance imaging and positron emission tomography for amyloid-β (11 C-PiB or 18 F-florbetapir) and tau (18 F-flortaucipir). 18 F-flortaucipir standardized uptake value ratios were calculated (t = 80-100 minutes, cerebellum gray matter reference). Voxelwise and region-of-interest group comparisons were performed in template space, with receiver operating characteristic curve analyses to assess single-subject discrimination. Qualitative comparisons with postmortem tau are reported in 1 patient who died 9 months after 18 F-flortaucipir.ResultsClinical PSP patients showed bilaterally elevated 18 F-flortaucipir uptake in globus pallidus, putamen, subthalamic nucleus, midbrain, and dentate nucleus relative to controls and PD patients (voxelwise p < 0.05 family wise error corrected). Globus pallidus binding best distinguished PSP patients from controls and PD (area under the curve [AUC] = 0.872 vs controls, AUC = 0.893 vs PD). PSP clinical severity did not correlate with 18 F-flortaucipir in any region. A patient with clinical PSP and pathological diagnosis of corticobasal degeneration had severe tau pathology in PSP-related brain structures with good correspondence between in vivo 18 F-flortaucipir and postmortem tau neuropathology.Interpretation18 F-flortaucipir uptake was elevated in PSP versus controls and PD patients in a pattern consistent with the expected distribution of tau pathology. Ann Neurol 2017;82:622-634
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18 F-flortaucipir tau positron emission tomography distinguishes established progressive supranuclear palsy from controls and Parkinson disease: A multicenter study.
Objective18 F-flortaucipir (formerly 18 F-AV1451 or 18 F-T807) binds to neurofibrillary tangles in Alzheimer disease, but tissue studies assessing binding to tau aggregates in progressive supranuclear palsy (PSP) have yielded mixed results. We compared in vivo 18 F-flortaucipir uptake in patients meeting clinical research criteria for PSP (n = 33) to normal controls (n = 46) and patients meeting criteria for Parkinson disease (PD; n = 26).MethodsParticipants underwent magnetic resonance imaging and positron emission tomography for amyloid-β (11 C-PiB or 18 F-florbetapir) and tau (18 F-flortaucipir). 18 F-flortaucipir standardized uptake value ratios were calculated (t = 80-100 minutes, cerebellum gray matter reference). Voxelwise and region-of-interest group comparisons were performed in template space, with receiver operating characteristic curve analyses to assess single-subject discrimination. Qualitative comparisons with postmortem tau are reported in 1 patient who died 9 months after 18 F-flortaucipir.ResultsClinical PSP patients showed bilaterally elevated 18 F-flortaucipir uptake in globus pallidus, putamen, subthalamic nucleus, midbrain, and dentate nucleus relative to controls and PD patients (voxelwise p < 0.05 family wise error corrected). Globus pallidus binding best distinguished PSP patients from controls and PD (area under the curve [AUC] = 0.872 vs controls, AUC = 0.893 vs PD). PSP clinical severity did not correlate with 18 F-flortaucipir in any region. A patient with clinical PSP and pathological diagnosis of corticobasal degeneration had severe tau pathology in PSP-related brain structures with good correspondence between in vivo 18 F-flortaucipir and postmortem tau neuropathology.Interpretation18 F-flortaucipir uptake was elevated in PSP versus controls and PD patients in a pattern consistent with the expected distribution of tau pathology. Ann Neurol 2017;82:622-634