scholarly journals No Influence of Age-Related Hearing Loss on Brain Amyloid-β

2021 ◽  
pp. 1-9
Author(s):  
Julia Z. Sarant ◽  
David C. Harris ◽  
Peter A. Busby ◽  
Christopher Fowler ◽  
Jurgen Fripp ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Pet Imaging ◽  
Clinical Sample ◽  
Amyloid Β ◽  
Carrier Status ◽  
Cognitive Assessments ◽  
Age Related ◽  
Positron Emission ◽  
Study Results ◽  
Study Participants

Background: Hearing loss is independently associated with a faster rate of cognitive decline in older adults and has been identified as a modifiable risk factor for dementia. The mechanism for this association is unknown, and there has been limited exploration of potential casual pathology. Objective: Our objective was to investigate whether there was an association between degree of audiometrically measured hearing loss (HL) and brain amyloid-β (Aβ) in a pre-clinical sample. Methods: Participants of the Australian Imaging and Biomarker Longitudinal Study (AIBL; n = 143) underwent positron emission tomography (PET) imaging and objective measurement of hearing thresholds within 5 years of imaging, as well as cognitive assessment within 2 years of imaging in this observational cohort study. Results: With one exception, study participants who had cognitive assessments within 2 years of their PET imaging (n = 113) were classified as having normal cognition. There was no association between cognitive scores and degree of hearing loss, or between cognitive scores and Aβ load. No association between HL and Aβ load was found once age was controlled for. As previously reported, positive Apolipoprotein E4 (APOE4) carrier status increased the risk of being Aβ positive (p = 0.002). Conclusion: Degree of HL was not associated with positive Aβ status.

The Transition of Mild Cognitive Impairment Over Time: An AV45- and FDG-PET Study of Reversion and Conversion Phenomena

2021 ◽  
Vol 18 ◽  
Author(s):  
Amir Ashraf-Ganjouei ◽  
Kamyar Moradi ◽  
Shahriar Faghani ◽  
AmirHussein Abdolalizadeh ◽  
Mohammadreza Khomeijani-Farahani ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Glucose Metabolism ◽  
Pet Imaging ◽  
Fdg Pet ◽  
Amyloid Β ◽  
Positron Emission ◽  
One Year ◽  
T Tau ◽  
Over Time

Background: Mild cognitive impairment (MCI) is a state between normal cognition and dementia. However, MCI diagnosis does not necessarily guarantee the progression to dementia. Since no previous study investigated brain positron emission tomography (PET) imaging of MCI-- to-normal reversion, we provided PET imaging of MCI-to-normal reversion using the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Methods: We applied comprehensive neuropsychological criteria (NP criteria), consisting of mem- ory, language, and attention/executive function domains, to include patients with a baseline diagno- sis of MCI (n=613). According to the criteria, the year 1 status of the patients was categorized into three groups (reversion: n=105, stable MCI: n=422, conversion: n=86). Demographic, neuropsycho- logical, genetic, CSF, and cognition biomarker variables were compared between the groups. Addi- tionally, after adjustment for confounding variables, the deposition pattern of amyloid-β and cere- bral glucose metabolism were compared between three groups via AV45- and FDG-PET modali- ties, respectively. Results: MCI reversion rate was 17.1% during one year of follow-up. The reversion group had the lowest frequency of APOE ε4+ subjects, the highest CSF level of amyloid-β, and the lowest CSF levels of t-tau and p-tau. Neuropsychological assessments were also suggestive of better cognitive performance in the reversion group. Patients with reversion to normal state had higher glucose metabolism in bilateral angular and left middle/inferior temporal gyri, when compared to those with stable MCI state. Meanwhile, lower amyloid-β deposition at baseline was observed in the fron- tal and parietal regions of the reverted subjects. On the other hand, the conversion group showed lower cerebral glucose metabolism in bilateral angular and bilateral middle/inferior temporal gyri compared to the stable MCI group, whereas the amyloid-β accumulation was similar between the groups. Conclusions: This longitudinal study provides novel insight regarding the application of PET imag- ing in predicting MCI transition over time.

scholarly journals A Longitudinal Analysis of the Association Between Subclinical Hearing Loss and Cognition

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 895-896
Author(s):  
Alexandria Irace ◽  
Nicole Armstrong ◽  
Jennifer Deal ◽  
Alexander Chern ◽  
Luigi Ferrucci ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Standardized Test ◽  
Verbal Learning ◽  
Covariance Structure ◽  
California Verbal Learning Test ◽  
Cognitive Assessments ◽  
Delayed Recall ◽  
Age Related ◽  
Learning Test ◽  
Age Related Hearing Loss

Abstract Several studies have demonstrated that age-related hearing loss (defined as >25 dB pure tone average [PTA]) is longitudinally associated with worse cognition. We aimed to investigate whether subclinical hearing loss (SCHL), or imperfect hearing traditionally categorized as normal (PTA ≤25 dB), may be similarly linked to cognitive decline. Subjects included cognitively normal adults ≥50 years old in the Baltimore Longitudinal Study of Aging with PTA ≤25 dB measured between January 1991 - September 1994 who had repeated cognitive assessments from January 1991 - November 2019 (n=263). The exposure was hearing based on the better ear PTA. The outcomes were standardized test scores in the following domains: learning/memory, mental status, executive function, visuospatial ability, and language. Multivariable linear-mixed effects models with random intercepts and slopes and unstructured variance-covariance structure were used to model the association between hearing and change in cognition over time, adjusting for baseline age, sex, years of education, and race. Mean age was 68.3 years (standard deviation [SD]=8.9) and follow-up ranged from 0-27.7 years (mean=12.5, SD=7.9). A 10-dB worsening in hearing was longitudinally associated with an annual decline of 0.016 SDs (95% confidence interval [CI]: 0.0002, 0.033) in California Verbal Learning Test (CVLT) short-delayed recall, 0.019 SDs (95% CI: 0.002, 0.036) in CVLT long-delayed recall, and 0.017 SDs (95% CI: 0.006, 0.028) in letter fluency after covariate adjustment. Poorer hearing among those with SCHL was associated with steeper declines in memory and verbal fluency scores. This relationship may begin at earlier levels of hearing loss than previously recognized.

scholarly journals Amyloid β-binding Bifunctional Chelators with Favorable Lipophilicity for 64Cu PET Imaging in Alzheimer’s Disease

2021 ◽  
Author(s):  
Yujue Wang ◽  
Truc T. Huynh ◽  
Hong-Jun Cho ◽  
Wang Yung-Ching ◽  
Buck E. Rogers ◽  
...  
Keyword(s):  
Binding Affinity ◽  
Pet Imaging ◽  
Ex Vivo ◽  
Amyloid Β ◽  
Specific Staining ◽  
Bifunctional Chelators ◽  
Biodistribution Studies ◽  
Positron Emission ◽  
D Values ◽  
Radiolabeled Compounds

Herein we report a new series of bifunctional chelators (BFCs) with high affinity for amyloid aggregates, strong binding affinity towards Cu(II) and favorable lipophilicity for potential blood-brain barrier (BBB) penetration. The alkyl carboxylate pendant arms offer up to three orders of magnitude higher binding affinity towards Cu(II) vs. the parent chelating fragment, and can generate fairly stable Cu complexes, including <sup>64</sup>Cu-radiolabeled compounds. Among the five compounds tested, the <sup>64</sup>Cu-YW-7 and <sup>64</sup>Cu-YW-10 complexes exhibit strong and specific staining of amyloid plaques in <i>ex vivo</i> autoradiography studies. Importantly, these compounds have promising partition coefficient (Log D) values of 0.91-1.26 and show moderate brain uptake in biodistribution studies using CD-1 mice. Overall, these BFCs could serve as lead compounds for the development of positron emission tomography (PET) imaging agents for AD diagnosis.

scholarly journals The GoAudio Quantitative Mobile Audiology Test Enhances Access to Clinical Hearing Assessments

2020 ◽  
Vol 29 (4) ◽  
pp. 887-897
Author(s):  
Alaa Koleilat ◽  
David P. Argue ◽  
Lisa A. Schimmenti ◽  
Stephen C. Ekker ◽  
Gayla L. Poling
Keyword(s):  
Health Care ◽  
Hearing Loss ◽  
Assessment Tool ◽  
Primary Study ◽  
Age Related ◽  
Hearing Thresholds ◽  
Study Results ◽  
Hearing Assessment ◽  
Hearing Health ◽  
Age Related Hearing Loss

Purpose Hearing loss is a common impairment of the human senses with an estimated 48 million American adults reporting some trouble hearing; however, access to hearing health care is limited. Detection of hearing loss through a mobile, handheld tool can provide an important access point and potentially expedited access to the continuum of hearing health care. Here, we determined that GoAudio, a portable, automated hearing assessment tool, can be used to identify individuals who require additional hearing evaluation in a clinical workflow. Method This initial study included 24 adults, ages 18–65 years ( M = 50, SD = 12), tested with GoAudio versus “gold-standard” clinical audiometry for eight frequencies to evaluate “real-world” applications. Participants utilized noise-canceling headphones combined with a tablet-based application for the GoAudio assessment. Results The primary study outcome measurements were the comparison of hearing thresholds (dB HL) from clinical audiometry and GoAudio. Results suggest that GoAudio is comparable to clinical audiometry for the identification of hearing loss at most frequencies (except 1 kHz for both ears and 2 kHz in the right ear). Upon stratifying data based on age, we identified that GoAudio is capable of identifying suspected age-related hearing loss or hearing thresholds greater than 30 dB HL at higher frequencies in both ears. Conclusion The study results support that GoAudio can be used effectively in clinical practice workflows as a reliable hearing assessment tool for the identification of hearing loss at the majority of frequencies outside a sound-treated booth and can detect characteristics of age-related hearing loss. Supplemental Material https://doi.org/10.23641/asha.13087682

scholarly journals Amyloid β-binding Bifunctional Chelators with Favorable Lipophilicity for 64Cu PET Imaging in Alzheimer’s Disease

2021 ◽  
Author(s):  
Yujue Wang ◽  
Truc T. Huynh ◽  
Hong-Jun Cho ◽  
Wang Yung-Ching ◽  
Buck E. Rogers ◽  
...  
Keyword(s):  
Binding Affinity ◽  
Pet Imaging ◽  
Ex Vivo ◽  
Amyloid Β ◽  
Specific Staining ◽  
Bifunctional Chelators ◽  
Biodistribution Studies ◽  
Positron Emission ◽  
D Values ◽  
Radiolabeled Compounds

Herein we report a new series of bifunctional chelators (BFCs) with high affinity for amyloid aggregates, strong binding affinity towards Cu(II) and favorable lipophilicity for potential blood-brain barrier (BBB) penetration. The alkyl carboxylate pendant arms offer up to three orders of magnitude higher binding affinity towards Cu(II) vs. the parent chelating fragment, and can generate fairly stable Cu complexes, including <sup>64</sup>Cu-radiolabeled compounds. Among the five compounds tested, the <sup>64</sup>Cu-YW-7 and <sup>64</sup>Cu-YW-10 complexes exhibit strong and specific staining of amyloid plaques in <i>ex vivo</i> autoradiography studies. Importantly, these compounds have promising partition coefficient (Log D) values of 0.91-1.26 and show moderate brain uptake in biodistribution studies using CD-1 mice. Overall, these BFCs could serve as lead compounds for the development of positron emission tomography (PET) imaging agents for AD diagnosis.

Plasma Amyloid-β Biomarker Associated with Cognitive Decline in Preclinical Alzheimer’s Disease

2020 ◽  
Vol 77 (3) ◽  
pp. 1057-1065
Author(s):  
Yen Ying Lim ◽  
Paul Maruff ◽  
Naoki Kaneko ◽  
James Doecke ◽  
Christopher Fowler ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Executive Function ◽  
Episodic Memory ◽  
High Performance ◽  
Amyloid Β ◽  
Cognitive Outcomes ◽  
Imaging Biomarkers ◽  
Cognitive Assessments ◽  
Positron Emission ◽  
The Relationship

Background: Using immunoprecipitation-mass spectrometry, we recently developed and validated a plasma composite biomarker for the assessment of amyloid-β (Aβ) levels. However, as yet, its relationship with clinical outcomes remains unclear. Objective: We aimed to examine the relationship between this plasma Aβ composite biomarker and cognitive function in cognitively normal older adults in two independent cohorts. Methods: Participants enrolled in the Australian Imaging, Biomarkers and Lifestyle (AIBL) study and the National Centre for Geriatrics and Gerontology (NCGG) study had undergone Aβ neuroimaging using positron emission tomography (PET), cognitive assessments and provided blood samples. We derived a high-performance plasma Aβ composite biomarker by immunoprecipitation with mass-spectrometry. Results: Both continuous and categorical measures of the plasma Aβ composite biomarker were significantly related to decline in episodic memory and executive function. The magnitude of effects of the plasma Aβ composite on episodic memory and executive function were comparable to that observed for the effects of PET Aβ levels on these same outcome measures. Conclusion: Several plasma Aβ biomarkers have been developed, but none have yet been applied to investigate their relationship with cognitive outcomes. Our results have important implications for the use of this biomarker in the detection of at-risk individuals.

18F-labelled CCR1-receptor antagonist is not suitable for imaging of Alzheimer's disease

2012 ◽  
Vol 51 (06) ◽  
pp. 239-243 ◽  
Author(s):  
V.A. Holthoff ◽  
P. Mäding ◽  
R. Bergmann ◽  
B. Pawelke ◽  
G. Holl ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Pet Imaging ◽  
Amyloid Β ◽  
Qualitative Evaluation ◽  
Compartment Analysis ◽  
Positron Emission ◽  
Enhanced Expression ◽  
Ccr1 Antagonist ◽  
The Brain

SummaryDiagnosis of Alzheimer’s disease (AD) with positron emission tomography (PET) using 18F-fluorodeoxyglucose (FDG) relies on typical alterations of brain glucose metabolism which are, however, not disease specific. Amyloid- β imaging has not entered clinical routine yet. Post mortem histological specimen of brain tissue from AD patients revealed enhanced expression of the chemotactic cytocine receptor 1 (CCR1). Participants, methods: CCR1-antagonist ZK811460 was labeled with fluorine-18 to explore its possible use as specific diagnostic tool in AD. Tracer characterization comprising PET imaging of brain and metabolite analysis was performed in AD patients and controls. Results: Neither qualitative evaluation nor quantitative compartment analysis of PET data did show any enhanced binding of the 18F-labeled CCR1-antagonist in the brain of AD patients or controls. Conclusion: 18F-ZK811460 did not fulfill the expectation as diagnostic tracer in PET imaging of AD.

scholarly journals Longitudinal Trajectories in Cortical Thickness and Volume Atrophy: Superior Cognitive Performance Does Not Protect Against Brain Atrophy in Older Adults

2021 ◽  
pp. 1-14
Author(s):  
Samantha L. Gardener ◽  
Michael Weinborn ◽  
Hamid R. Sohrabi ◽  
James D. Doecke ◽  
Pierrick Bourgeat ◽  
...  
Keyword(s):  
Older Adults ◽  
Cognitive Performance ◽  
Cortical Thickness ◽  
Amyloid Β ◽  
Discovery Phase ◽  
Age Related ◽  
Small Subgroup ◽  
Study Results ◽  
Potential Factors ◽  
High Level

Background: Previous research has identified a small subgroup of older adults that maintain a high level of cognitive functioning well into advanced age. Investigation of those with superior cognitive performance (SCP) for their age is important, as age-related decline has previously been thought to be inevitable. Objective: Preservation of cortical thickness and volume was evaluated in 76 older adults with SCP and 100 typical older adults (TOAs) assessed up to five times over six years. Methods: Regions of interest (ROIs) found to have been associated with super-aging status (a construct similar to SCP status) in previous literature were investigated, followed by a discovery phase analyses of additional regions. SCPs were aged 70 + at baseline, scoring at/above normative memory (CVLT-II) levels for demographically similar individuals aged 30–44 years old, and in the unimpaired range for all other cognitive domains over the course of the study. Results: In linear mixed models, following adjustment for multiple comparisons, there were no significant differences between rates of thinning or volume atrophy between SCPs and TOAs in previously identified ROIs, or the discovery phase analyses. With only amyloid-β negative individuals in the analyses, again there were no significant differences between SCPs and TOAs. Conclusion: The increased methodological rigor in classifying groups, together with the influence of cognitive reserve, are discussed as potential factors accounting for our findings as compared to the extant literature on those with superior cognitive performance for their age.

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