scholarly journals Evaluation of PiB visual interpretation with CSF Aβ and longitudinal SUVR in J-ADNI study

2019 ◽  
Vol 34 (2) ◽  
pp. 108-118 ◽  
Author(s):  
Yusuke Okada ◽  
◽  
Takashi Kato ◽  
Kaori Iwata ◽  
Yasuyuki Kimura ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Stage ◽  
Amyloid Pet ◽  
Negative Group ◽  
Visual Interpretation ◽  
Positive Group ◽  
Amyloid Accumulation ◽  
Over Time

Abstract Objective The objectives of the present study were to investigate (1) whether trinary visual interpretation of amyloid positron emission tomography (PET) imaging (negative/equivocal/positive) reflects quantitative amyloid measurements and the time course of 11C-Pittsburgh compound B (PiB) amyloid accumulation, and (2) whether visually equivocal scans represent an early stage of the Alzheimer’s disease (AD) continuum in terms of an intermediate state of quantitative amyloid measurements and the changes in amyloid accumulation over time. Methods From the National Bioscience Database Center Human Database of the Japanese Alzheimer’s Disease Neuroimaging Initiative, we selected 133 individuals for this study including 33 with Alzheimer’s disease dementia (ADD), 52 with late mild cognitive impairment (LMCI), and 48 cognitively normal (CN) subjects who underwent clinical assessment, PiB PET, and structural magnetic resonance imaging (MRI) with 2 or 3-years of follow-up. Sixty-eight of the 133 individuals underwent cerebrospinal fluid amyloid-β1-42 (CSF-Ab42) analysis at baseline. The standard uptake value ratio (SUVR) of PiB PET was calculated with a method using MRI at each visit. The cross-sectional values, longitudinal changes in SUVR, and baseline CSF-Ab42 were compared among groups, which were categorized based on trinary visual reads of amyloid PET (negative/equivocal/positive). Results From the trinary visual interpretation of the PiB PET images, 55 subjects were negative, 8 were equivocal, and 70 were positive. Negative interpretation was most frequent in the CN group (70.8/10.4/18.8%: negative/equivocal/positive), and positive was most frequent in the LMCI group (34.6/1.9/63.5%) and in the ADD group (9.1/6.1/84.8%). The baseline SUVRs were 1.08 ± 0.06 in the negative group, 1.23 ± 0.15 in the equivocal group, and 1.86 ± 0.31 in the positive group (F = 174.9, p < 0.001). The baseline CSF-Ab42 level was 463 ± 112 pg/mL in the negative group, 383 ± 125 pg/mL in the equivocal group, and 264 ± 69 pg/mL in the positive group (F = 37, p < 0.001). Over the 3-year follow-up, annual changes in SUVR were − 0.00 ± 0.02 in the negative group, 0.02 ± 0.02 in the equivocal group, and 0.04 ± 0.07 in the positive group (F = 8.4, p < 0.001). Conclusions Trinary visual interpretation (negative/equivocal/positive) of amyloid PET imaging reflects quantitative amyloid measurements evaluated with PET and the CSF amyloid test as well as the amyloid accumulation over time evaluated with PET over 3 years. Subjects in the early stage of the AD continuum could be identified with an equivocal scan, because they showed intermediate quantitative amyloid PET, CSF measurements, and the amyloid accumulation over time.

Elucidating the risk factors for progression from amyloid-negative amnestic mild cognitive impairment to dementia

2020 ◽  
Vol 17 ◽  
Author(s):  
Hyung-Ji Kim ◽  
Jae-Hong Lee ◽  
E-nae Cheong ◽  
Sung-Eun Chung ◽  
Sungyang Jo ◽  
...  
Keyword(s):  
Risk Factors ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Amnestic Mild Cognitive Impairment ◽  
Amyloid Pet ◽  
Clinical Progression ◽  
Amnestic Mci

Background: Amyloid PET allows for the assessment of amyloid β status in the brain, distinguishing true Alzheimer’s disease from Alzheimer’s disease-mimicking conditions. Around 15–20% of patients with clinically probable Alzheimer’s disease have been found to have no significant Alzheimer’s pathology on amyloid PET. However, a limited number of studies had been conducted this subpopulation in terms of clinical progression. Objective: We investigated the risk factors that could affect the progression to dementia in patients with amyloid-negative amnestic mild cognitive impairment (MCI). Methods: This study was a single-institutional, retrospective cohort study of patients over the age of 50 with amyloidnegative amnestic MCI who visited the memory clinic of Asan Medical Center with a follow-up period of more than 36 months. All participants underwent brain magnetic resonance imaging (MRI), detailed neuropsychological testing, and fluorine-18[F18]-florbetaben amyloid PET. Results: During the follow-up period, 39 of 107 patients progressed to dementia from amnestic MCI. In comparison with the stationary group, the progressed group had a more severe impairment in verbal and visual episodic memory function and hippocampal atrophy, which showed an Alzheimer’s disease-like pattern despite the lack of evidence for significant Alzheimer’s disease pathology. Voxel-based morphometric MRI analysis revealed that the progressed group had a reduced gray matter volume in the bilateral cerebellar cortices, right temporal cortex, and bilateral insular cortices. Conclusion: Considering the lack of evidence of amyloid pathology, clinical progression of these subpopulation may be caused by other neuropathologies such as TDP-43, abnormal tau or alpha synuclein that lead to neurodegeneration independent of amyloid-driven pathway. Further prospective studies incorporating biomarkers of Alzheimer’s diseasemimicking dementia are warranted.

The Trajectory of Cerebrospinal Fluid Growth-Associated Protein 43 in the Alzheimer’s Disease Continuum: A Longitudinal Study

2021 ◽  
pp. 1-12
Author(s):  
Heng Zhang ◽  
Diyang Lyu ◽  
Jianping Jia ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Amyloid Β ◽  
Dementia Patients ◽  
Positron Emission ◽  
Potential Biomarker ◽  
Synaptic Degeneration ◽  
Over Time

Background: Synaptic degeneration has been suggested as an early pathological event that strongly correlates with severity of dementia in Alzheimer’s disease (AD). However, changes in longitudinal cerebrospinal fluid (CSF) growth-associated protein 43 (GAP-43) as a synaptic biomarker in the AD continuum remain unclear. Objective: To assess the trajectory of CSF GAP-43 with AD progression and its association with other AD hallmarks. Methods: CSF GAP-43 was analyzed in 788 participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI), including 246 cognitively normal (CN) individuals, 415 individuals with mild cognitive impairment (MCI), and 127 with AD dementia based on cognitive assessments. The associations between a multimodal classification scheme with amyloid-β (Aβ), tau, and neurodegeneration, and changes in CSF GAP-43 over time were also analyzed. Results: CSF GAP-43 levels were increased at baseline in MCI and dementia patients, and increased significantly over time in the preclinical (Aβ-positive CN), prodromal (Aβ-positive MCI), and dementia (Aβ-positive dementia) stages of AD. Higher levels of CSF GAP-43 were also associated with higher CSF phosphorylated tau (p-tau) and total tau (t-tau), cerebral amyloid deposition and hypometabolism on positron emission tomography, the hippocampus and middle temporal atrophy, and cognitive performance deterioration at baseline and follow-up. Furthermore, CSF GAP-43 may assist in effectively predicting the probability of dementia onset at 2- or 4-year follow-up. Conclusion: CSF GAP-43 can be used as a potential biomarker associated with synaptic degeneration in subjects with AD; it may also be useful for tracking the disease progression and for monitoring the effects of clinical trials.

IC-P-156: Baseline amyloid PET imaging, longitudinal amyloid accumulation, and Tau PET imaging in preclinical Alzheimer's disease

2015 ◽  
Vol 11 (7S_Part_2) ◽  
pp. P105-P105
Author(s):  
Aaron P. Schultz ◽  
Elizabeth C. Mormino ◽  
Jasmeer P. Chhatwal ◽  
Molly LaPoint ◽  
Alex S. Dagley ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Pet Imaging ◽  
Amyloid Pet ◽  
Preclinical Alzheimer’S Disease ◽  
Amyloid Accumulation ◽  
Tau Pet ◽  
Tau Pet Imaging ◽  
Amyloid Pet Imaging

scholarly journals Multi-method investigation of factors influencing amyloid onset and impairment in three cohorts

2021 ◽  
Author(s):  
Tobey J. Betthauser ◽  
Murat Bilgel ◽  
Rebecca L. Koscik ◽  
Bruno M. Jedynak ◽  
Yang An ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Apolipoprotein E ◽  
Cox Regression ◽  
Amyloid Pet ◽  
Onset Age ◽  
Longitudinal Course ◽  
Modeling Methods ◽  
Amyloid Accumulation ◽  
Apolipoprotein E Genotype

AbstractAlzheimer’s disease biomarkers are becoming increasingly important for characterizing the longitudinal course of disease, predicting the timing of clinical and cognitive symptoms, and for recruitment and treatment monitoring in clinical trials. In this work, we develop and evaluate three methods for modeling the longitudinal course of amyloid accumulation in three cohorts using amyloid PET imaging. We then use these novel approaches to investigate factors that influence the timing of amyloid onset and the timing from amyloid onset to impairment onset in the Alzheimer’s disease continuum.Data were acquired from the Alzheimer’s Disease Neuroimaging Initiative (ADNI), the Baltimore Longitudinal Study of Aging (BLSA) and the Wisconsin Registry for Alzheimer’s Prevention (WRAP). Amyloid PET was used to assess global amyloid burden. Three methods were evaluated for modeling amyloid accumulation using 10-fold cross-validation and hold-out validation where applicable. Estimated amyloid onset age was compared across all three modeling methods and cohorts. Cox regression and accelerated failure time models were used to investigate whether sex, apolipoprotein E genotype and e4 carriage were associated with amyloid onset age in all cohorts. Cox regression was used to investigate whether apolipoprotein E (e4 carriage and e3e3, e3e4, e4e4 genotypes), sex or age of amyloid onset were associated with the time from amyloid onset to impairment onset (global Clinical Dementia Rating ≥1) in a subset of 595 ADNI participants that were not impaired prior to amyloid onset.Model prediction and estimated amyloid onset age were similar across all three amyloid modeling methods. Sex and apolipoprotein E-e4 carriage were not associated with PET-measured amyloid accumulation rates. Apolipoprotein E genotype and e4 carriage, but not sex, were associated with amyloid onset age such that e4 carriers became amyloid positive at an earlier age compared to non-carriers, and greater e4 dosage was associated with an earlier amyloid onset age. In the ADNI, e4 carriage, being female and a later amyloid onset age were all associated with a shorter time from amyloid onset to impairment onset. The risk of impairment onset due to age of amyloid onset was nonlinear and accelerated for amyloid onset age >65. These findings demonstrate the feasibility of modeling longitudinal amyloid accumulation to enable individualized estimates of amyloid onset age from amyloid PET imaging. These estimates provide a more direct way to investigate the role of amyloid and other factors that influence the timing of clinical impairment in Alzheimer’s disease.

Longitudinal changes in awareness over 36 months in patients with mild Alzheimer's disease

2014 ◽  
Vol 27 (1) ◽  
pp. 95-102 ◽  
Author(s):  
Asmus Vogel ◽  
Frans Boch Waldorff ◽  
Gunhild Waldemar
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Mmse Score ◽  
Neuropsychiatric Symptoms ◽  
Rapid Decline ◽  
Longitudinal Changes ◽  
Moderate Dementia ◽  
Over Time

ABSTRACTBackground:Longitudinal changes in awareness in dementia have been studied with short follow-up time and mostly in small patient groups (including patients with moderate dementia). We investigated awareness in patients with mild Alzheimer's disease (AD) over 36 months and studied if a decline in awareness was associated with decline in cognition and increase in neuropsychiatric symptoms.Methods:Awareness was measured on a categorical scale in 95 AD patients (age ≥50 years, Mini-Mental State Examination (MMSE) score ≥20). Awareness was rated at three time points (follow-up at 12 and 36 months) where MMSE, Neuropsychiatric Inventory (NPI-Q), and Cornell scale for Depression in Dementia also were applied.Results:At 12 months, 26% had lower awareness rating as compared to baseline and at 36 months lower awareness ratings were found in 39%. At both visits, 16% had higher awareness rating as compared to baseline. Patients with lower awareness at 36 months as compared to baseline had a more rapid increase in NPI-Q score (p = 0.002) over 36 months as compared to patients with stable or improved awareness over 36 months. A more rapid decline in MMSE score was observed for patients with lower awareness at 36 months (as compared to baseline) but only when compared to patients in whom awareness improved over time.Conclusions:The results show essentially no clear relationship between cognitive decline over three years and awareness. In some cases, awareness remained stable or even improved despite significant cognitive decline. In the subgroup where awareness declined over time, overall ratings of neuropsychiatric symptoms declined more rapidly than in the remaining patients.

scholarly journals Pilot Evaluation of the Unsupervised, At-Home Cogstate Brief Battery in ADNI-2

2021 ◽  
pp. 1-11
Author(s):  
Chris J. Edgar ◽  
Eric Siemers ◽  
Paul Maruff ◽  
Ronald C. Petersen ◽  
Paul S. Aisen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Bring Your Own Device ◽  
Cohen’S D ◽  
Small Effect Size ◽  
Cohen's D ◽  
Over Time ◽  
At Home

Background: There is a need for feasible, scalable assessments to detect cognitive impairment and decline. The Cogstate Brief Battery (CBB) is validated for Alzheimer’s disease (AD) and in unsupervised and bring your own device contexts. The CBB has shown usability for self-completion in the home but has not been employed in this way in a multisite clinical trial in AD. Objective: The objective of the pilot was to evaluate feasibility of at-home, self-completion of the CBB in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) over 24 months. Methods: The CBB was included as a pilot for cognitively normal (CN) and mild cognitive impairment (MCI) participants in ADNI-2, invited to take the assessment in-clinic, then at at-home over a period of 24 months follow-up. Data were analyzed to explore acceptability/usability, concordance of in-clinic and at-home assessment, and validity. Results: Data were collected for 104 participants (46 CN, 51 MCI, and 7 AD) who consented to provide CBB data. Subsequent analyses were performed for the CN and MCI groups only. Test completion rates were 100%for both the first in-clinic supervised and first at-home unsupervised assessments, with few repeat performances required. However, availability follow-up data declined sharply over time. Good concordance was seen between in-clinic and at-home assessments, with non-significant and small effect size differences (Cohen’s d between -0.04 and 0.28) and generally moderate correlations (r = 0.42 to 0.73). Known groups validity was also supported (11/16 comparisons with Cohen’s d≥0.3). Conclusion: These data demonstrate the feasibility of use for the CBB for unsupervised at-home, testing, including MCI groups. Optimal approaches to the application of assessments to support compliance over time remain to be determined.

Perceptions of change over time in early-stage Alzheimer's disease

Dementia ◽  
2005 ◽  
Vol 4 (4) ◽  
pp. 487-520 ◽  
Author(s):  
Linda Clare ◽  
Ilona Roth ◽  
Rebekah Pratt
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Stage ◽  
Change Over Time ◽  
Over Time

scholarly journals Falls Associate with Neurodegenerative Changes in ATN Framework of Alzheimer’s Disease

2020 ◽  
Vol 77 (2) ◽  
pp. 745-752
Author(s):  
Audrey Keleman ◽  
Julie K. Wisch ◽  
Rebecca M. Bollinger ◽  
Elizabeth A. Grant ◽  
Tammie L. Benzinger ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Brain Connectivity ◽  
Hippocampal Volume ◽  
Cross Sectional Study ◽  
Amyloid Pet ◽  
Resting State Functional Connectivity ◽  
Cross Sectional ◽  
Preclinical Ad ◽  
Amyloid Accumulation

Background: Behavioral markers for Alzheimer’s disease (AD) are not included within the widely used amyloid-tau-neurodegeneration framework. Objective: To determine when falls occur among cognitively normal (CN) individuals with and without preclinical AD. Methods: This cross-sectional study recorded falls among CN participants (n = 83) over a 1-year period. Tailored calendar journals recorded falls. Biomarkers including amyloid positron emission tomography (PET) and structural and functional magnetic resonance imaging were acquired within 2 years of fall evaluations. CN participants were dichotomized by amyloid PET (using standard cutoffs). Differences in amyloid accumulation, global resting state functional connectivity (rs-fc) intra-network signature, and hippocampal volume were compared between individuals who did and did not fall using Wilcoxon rank sum tests. Among preclinical AD participants (amyloid-positive), the partial correlation between amyloid accumulation and global rs-fc intra-network signature was compared for those who did and did not fall. Results: Participants who fell had smaller hippocampal volumes (p = 0.04). Among preclinical AD participants, those who fell had a negative correlation between amyloid uptake and global rs-fc intra-network signature (R = –0.75, p = 0.012). A trend level positive correlation was observed between amyloid uptake and global rs-fc intra-network signature (R = 0.70, p = 0.081) for preclinical AD participants who did not fall. Conclusion: Falls in CN older adults correlate with neurodegeneration biomarkers. Participants without falls had lower amyloid deposition and preserved global rs-fc intra-network signature. Falls most strongly correlated with presence of amyloid and loss of brain connectivity and occurred in later stages of preclinical AD.

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