Plasma Amyloid Beta Concentrations in Aged and Cognitively Impaired Pet Dogs.
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ABSTRACT:
SUBMITTER: Panek WK
PROVIDER: S-EPMC7855498 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:IntroductionBeta-amyloid (Aβ) deposition, a hallmark of Alzheimer's disease (AD), begins before dementia and is an important factor in mild cognitive impairment (MCI). Aβ deposition is a recognized risk factor for various cognitive impairments and has been reported to affect motor performance as well. This study aimed to identify the linguistic, visuospatial, and kinematic characteristics evident in the writing performance of patients with cognitive impairment (CI) who exhibit Aβ deposition.MethodsA total of 31 patients diagnosed with amnestic mild cognitive impairment (aMCI) with Aβ deposition, 26 patients with Alzheimer's-type dementia, and 33 healthy control (HC) participants without deposition were administered tasks involving dictation of 60 regular words, irregular words, and non-words consisting of 1-4 syllables. Responses from all participants were collected and analyzed through digitized writing tests and analysis tools.ResultsIn terms of linguistic aspects, as cognitive decline progressed, performance in the dictation of irregular words decreased, with errors observed in substituting the target grapheme with other graphemes. The aMCI group frequently exhibited corrective aspects involving letter rewriting during the task. In terms of visuospatial aspects, the AD group displayed more errors in grapheme combination compared to the HC group. Lastly, in the kinematic aspects, both the aMCI group and the AD group exhibited slower writing speeds compared to the HC group.DiscussionThe findings suggest that individuals in the CI group exhibited lower performance in word dictation tasks than those in the HC group, and these results possibly indicate complex cognitive-language-motor deficits resulting from temporal-parietal lobe damage, particularly affecting spelling processing. These results provide valuable clinical insights into understanding linguistic-visuospatial-kinematic aspects that contribute to the early diagnosis of CI with Aβ deposition.
| S-EPMC10518411 | biostudies-literature
Project description:Background/objectivesDisclosure of Alzheimer's disease (AD) risk information to cognitively unimpaired older adults may become more common if preclinical AD is shown to be identifiable and amenable to treatment. Little, however, is known about how families will react to this information.Design and settingSemi-structured telephonic interviews.ParticipantsSeventy study partners (mean age = 68 [±11]; 50% female; 70% spouses/significant others; 18% children, siblings; 12% friends) of cognitively unimpaired adults who learned a personalized AD dementia risk estimate and an amyloid-β PET scan result through their participation in preclinical AD research.MeasurementInterviewees were asked about their desire for information regarding their family member's AD dementia risk, baseline expectations of risk, understanding of amyloid-β PET scan results, and the impact of AD dementia risk information on emotions, health behaviors, and future plans, as well as on perceptions of their family member's or friend's memory.ResultsInterviewees generally understood the AD dementia risk information (83%) and considered it valuable (75%). Risk information perceived as favorable elicited feelings of happiness and relief; unfavorable information elicited disappointment, as well as increased awareness of the participants' memory and monitoring for incipient changes in cognition. While noting that AD dementia risk information was not medically actionable at this time due to the lack of disease-modifying therapies, some interviewees described changes to their family members' and their own health behaviors and future plans.ConclusionGuidelines for the disclosure of AD dementia risk estimates and biomarker results to cognitively unimpaired adults should account for the needs and interests of individuals and their family members, who may step into a pre-caregiver role.
| S-EPMC8595546 | biostudies-literature
Project description:IntroductionAlzheimer's Prevention Initiative Generation Study 1 evaluated amyloid beta (Aβ) active immunotherapy (vaccine) CAD106 and BACE-1 inhibitor umibecestat in cognitively unimpaired 60- to 75-year-old participants at genetic risk for Alzheimer's disease (AD). The study was reduced in size and terminated early. Results from the CAD106 cohort are presented.MethodsSixty-five apolipoprotein E ε4 homozygotes with/without amyloid deposition received intramuscular CAD106 450 μg (n = 42) or placebo (n = 23) at baseline; Weeks 1, 7, 13; and quarterly; 51 of them had follow-up Aβ positron emission tomography (PET) scans at 18 to 24 months.ResultsCAD106 induced measurable serum Aβ immunoglobulin G titers in 41/42 participants, slower rates of Aβ plaque accumulation (mean [standard deviation] annualized change from baseline in amyloid PET Centiloid: -0.91[5.65] for CAD106 versus 8.36 [6.68] for placebo; P < 0.001), and three amyloid-related imaging abnormality cases (one symptomatic).DiscussionDespite early termination, these findings support the potential value of conducting larger prevention trials of Aβ active immunotherapies in individuals at risk for AD.HighlightsThis was the first amyloid-lowering prevention trial in persons at genetic risk of late-onset Alzheimer's disease (AD). Active immunotherapy targeting amyloid (CAD106) was tested in this prevention trial. CAD106 significantly slowed down amyloid plaque deposition in apolipoprotein E homozygotes. CAD106 was generally safe and well tolerated, with only three amyloid-related imaging abnormality cases (one symptomatic). Such an approach deserves further evaluation in larger AD prevention trials.
| S-EPMC10984441 | biostudies-literature
Project description:BackgroundLittle research exists on the role of β-amyloid PET scans as part of Alzheimer's diagnostic tests and documentation of end-of-life preferences for persons with cognitive impairment. The study objectives were to examine the association of amyloid PET scan results (elevated vs. not elevated amyloid levels) and diagnostic category (mild cognitive impairment vs. dementia) with the likelihood of having an advance directive (reported a median of 4.5 months post-scan); to explore perceptions of PET scan results and their influence on planning for the future among persons with cognitive impairment and their care partners.MethodsSequential, explanatory mixed-methods design using data from dyads in the CARE-IDEAS study: advance directives as a factor of diagnostic category and scan result using multivariable logistic regression models; thematic analysis of semi-structured interviews with persons with cognitive impairment and care partners to explore how scan results influenced documentation of future healthcare preferences. Participants included 1784 persons with cognitive impairment and care partners from the CARE-IDEAS study, and a subsample of 100 semi-structured telephone interviews.Results81.6% of dyads reported an advance directive. Non-Hispanic, White participants had higher rates of advance directives. There was no significant association between having an advance directive and scan results. Qualitative analysis provided insight into perceived urgency to have advance directives, evolving healthcare preferences, and the context of completing advance directives.ConclusionsAlthough amyloid PET scans prompted persons with cognitive impairment and care partners to consider progressive cognitive impairment as part of evolving healthcare preferences, we found substantial variability in the perceived urgency of documentation.
| S-EPMC9638311 | biostudies-literature
Project description:Osteoporosis and Alzheimer's disease (AD) mainly affect older individuals, and the possibility of an underlying link contributing to their shared epidemiological features has rarely been investigated. In the current study, we investigated the association between levels of plasma sclerostin (SOST), a protein primarily produced by bone, and brain amyloid-beta (Aβ) load, a pathological hallmark of AD. The study enrolled participants meeting a set of screening inclusion and exclusion criteria and were stratified into Aβ- (n = 65) and Aβ+ (n = 35) according to their brain Aβ load assessed using Aβ-PET (positron emission tomography) imaging. Plasma SOST levels, apolipoprotein E gene (APOE) genotype and several putative AD blood-biomarkers including Aβ40, Aβ42, Aβ42/Aβ40, neurofilament light (NFL), glial fibrillary acidic protein (GFAP), total tau (t-tau) and phosphorylated tau (p-tau181 and p-tau231) were detected and compared. It was found that plasma SOST levels were significantly higher in the Aβ+ group (71.49 ± 25.00 pmol/L) compared with the Aβ- group (56.51 ± 22.14 pmol/L) (P < 0.01). Moreover, Spearman's correlation analysis showed that plasma SOST concentrations were positively correlated with brain Aβ load (ρ = 0.321, P = 0.001). Importantly, plasma SOST combined with Aβ42/Aβ40 ratio significantly increased the area under the curve (AUC) when compared with using Aβ42/Aβ40 ratio alone (AUC = 0.768 vs 0.669, P = 0.027). In conclusion, plasma SOST levels are elevated in cognitively unimpaired older adults at high risk of AD and SOST could complement existing plasma biomarkers to assist in the detection of preclinical AD.
| S-EPMC10477312 | biostudies-literature
Project description:Alzheimer's disease biomarkers are primarily evaluated through MRI, PET and CSF methods in order to diagnose and monitor disease. Recently, advances in the assessment of blood-based biomarkers have shown promise for simple, inexpensive, accessible and minimally invasive tools with diagnostic and prognostic value for Alzheimer's disease. Most recently, plasma phosphorylated tau181 has shown excellent performance. The relationship between plasma phosphorylated tau181 and cerebral metabolic dysfunction assessed by [18F]fluorodeoxyglucose PET in Alzheimer's disease is still unknown. This study was performed on 892 older individuals (297 cognitively unimpaired; 595 cognitively impaired) from the Alzheimer's Disease Neuroimaging Initiative cohort. Plasma phosphorylated tau181 was assessed using single molecular array technology and metabolic dysfunction was indexed by [18F]fluorodeoxyglucose PET. Cross-sectional associations between plasma and CSF phosphorylated tau181 and [18F]fluorodeoxyglucose were assessed using voxelwise linear regression models, with individuals stratified by diagnostic group and by β-amyloid status. Associations between baseline plasma phosphorylated tau181 and longitudinal (24 months) rate of brain metabolic decline were also assessed in 389 individuals with available data using correlations and voxelwise regression models. Plasma phosphorylated tau181 was elevated in β-amyloid positive and cognitively impaired individuals as well as in apolipoprotein E ε4 carriers and was significantly associated with age, worse cognitive performance and CSF phosphorylated tau181. Cross-sectional analyses showed strong associations between plasma phosphorylated tau181 and [18F]fluorodeoxyglucose PET in cognitively impaired and β-amyloid positive individuals. Voxelwise longitudinal analyses showed that baseline plasma phosphorylated tau181 concentrations were significantly associated with annual rates of metabolic decline in cognitively impaired individuals, bilaterally in the medial and lateral temporal lobes. The associations between plasma phosphorylated tau181 and reduced brain metabolism, primarily in cognitively impaired and in β-amyloid positive individuals, supports the use of plasma phosphorylated tau181 as a simple, low-cost, minimally invasive and accessible tool to both assess current and predict future metabolic dysfunction associated with Alzheimer's disease, comparatively to PET, MRI and CSF methods.
| S-EPMC8088291 | biostudies-literature
Project description:ImportanceClinical guidelines currently recommend against amyloid imaging for cognitively unimpaired persons. The goal of Alzheimer's disease (AD) prevention, together with advances in understanding the pathophysiology of AD, however, has led to trials testing drugs in cognitively unimpaired persons who show evidence of AD biomarkers. Assuming the eventual success of such trials, millions of patients will be affected. There is a need to understand the effects of biomarker disclosure on those individuals.DesignThe Study of Knowledge and Reactions to Amyloid Testing (SOKRATES) involved 2 semi-structured telephone interviews with individuals who received amyloid PET scan results as part of screening for research participation. Post-disclosure interviews were conducted at 4 to 12 weeks and again 1 year later. Data were collected from November 5, 2014 to November 30, 2016. Interviews were transcribed and coded in NVivo 12.0.Participants80 adults aged 65 and older: 50 who received "elevated" and 30 who received "not-elevated" amyloid PET scan results.Main outcomesInterviews examined four domains: (1) comprehension of the amyloid PET scan result; (2) implications of the result for sense of self, memory, and future; (3) sharing of results with others; and (4) AD risk-reduction behaviors.ResultsParticipants who received an elevated amyloid PET scan result viewed the result as more serious and sensitive than other medical test results given its unique implications for identity, self-determination, and stigma. In contrast, participants who received a not-elevated amyloid PET scan result described feeling relief and reinterpreted perceived memory impairments as normal aging. Participants with elevated amyloid reported contemplating and making more changes to health behaviors and future plans than their peers with not-elevated amyloid.ConclusionsClinical practice in the diagnosis and treatment of persons with preclinical AD, a stage of the disease defined by the presence of biomarkers in the absence of cognitive impairment, will need to address matters of identity, stigma, and life-planning.
| S-EPMC7018056 | biostudies-literature
Project description:ObjectivesRecent studies regarding the relationships between plasma amyloid-β (Aβ) levels and cognitive performance had inconsistent results. In this study, we aimed to characterize the relationship between cognitive decline and plasma Aβ levels in a large-sample cognitively normal population.MethodsThis population-based, prospective cohort study included 1,240 participants with normal cognition. The Mini-Mental State Examination (MMSE) was used to assess cognitive function at baseline and 2 years later. Restricted cubic splines, multivariate logistic regression, and multivariate linear regression models were used to evaluate the type of relationship between cognitive decline during the 2-year follow-up period and plasma Aβ levels (Aβ40, Aβ42, and Aβ42 / 40).ResultsParticipants with moderate Aβ40 levels had the highest risk of cognitive decline during a 2-year follow-up relative to individuals with low Aβ40 [odds ratio (OR): 0.60, 95% confidence interval (CI): 0.45-0.81, p < 0.001] or high Aβ40 (OR: 0.65, 95% CI: 0.49-0.87, p = 0.004) levels. The association between Aβ40 and cognitive decline did not depend on sex, education level, or APOE ε4 status. There was an interaction found between age (≤ 65 and > 65 years) and Aβ40 (p for interaction = 0.021). In individuals older than 65 years, there was a positive linear relationship between plasma Aβ40 and cognitive decline (OR: 1.02, 95% CI: 1.00-1.04, p = 0.027). For participants ≤ 65 years old, the lower Aβ40 and higher Aβ40 groups had a lower risk of cognitive decline than the medium Aβ40 group (OR: 0.69, 95% CI: 0.50-0.94, p = 0.02; OR: 0.63, 95% CI: 0.45-0.86, p = 0.004). None of relationship between plasma Aβ42, Aβ42 / 40 and cognitive decline was found during a 2-year follow-up.ConclusionThe relationship between plasma Aβ40 and cognitive decline was not linear, but an inverted-U shape in a cognitively normal population. The underlying mechanism requires further investigation.
| S-EPMC7516983 | biostudies-literature
Project description:Evidence suggests that lightly myelinated cortical regions are vulnerable to aging and Alzheimer's disease (AD). However, it remains unknown whether plasma markers of amyloid and neurodegeneration are related to deficits in intracortical myelin content, and whether this relationship, in turn, is associated with altered patterns of resting-state functional connectivity (rs-FC). To shed light into these questions, plasma levels of amyloid-β fragment 1-42 (Aβ1-42) and neurofilament light chain (NfL) were measured using ultra-sensitive single-molecule array (Simoa) assays, and the intracortical myelin content was estimated with the ratio T1-weigthed/T2-weighted (T1w/T2w) in 133 cognitively normal older adults. We assessed: (i) whether plasma Aβ1-42 and/or NfL levels were associated with intracortical myelin content at different cortical depths and (ii) whether cortical regions showing myelin reductions also exhibited altered rs-FC patterns. Surface-based multiple regression analyses revealed that lower plasma Aβ1-42 and higher plasma NfL were associated with lower myelin content in temporo-parietal-occipital regions and the insular cortex, respectively. Whereas the association with Aβ1-42 decreased with depth, the NfL-myelin relationship was most evident in the innermost layer. Older individuals with higher plasma NfL levels also exhibited altered rs-FC between the insula and medial orbitofrontal cortex. Together, these findings establish a link between plasma markers of amyloid/neurodegeneration and intracortical myelin content in cognitively normal older adults, and support the role of plasma NfL in boosting aberrant FC patterns of the insular cortex, a central brain hub highly vulnerable to aging and neurodegeneration.
| S-EPMC9247578 | biostudies-literature
Project description:Objective: To define resilience metrics for cognitive decline based on plasma and cerebrospinal fluid (CSF) amyloid-β (Aβ) and examine the demographic, genetic, and neuroimaging factors associated with interindividual differences among metrics of resilience and to demonstrate the ability of such metrics to predict the diagnostic conversion to mild cognitive impairment (MCI). Methods: In this study, cognitively normal (CN) participants with Aβ-positive were included from the Sino Longitudinal Study on Cognitive Decline (SILCODE, n = 100) and Alzheimer's Disease Neuroimaging Initiative (ADNI, n = 144). Using a latent variable model of data, metrics of resilience [brain resilience (BR), cognitive resilience (CR), and global resilience (GR)] were defined based on the plasma Aβ and CSF Aβ. Linear regression analyses were applied to investigate the association between characteristics of individuals (age, sex, educational level, genetic, and neuroimaging factors) and their resilience. The plausibility of these metrics was tested using linear mixed-effects models and Cox regression models in longitudinal analyses. We also compared the effectiveness of these metrics with conventional metrics in predicting the clinical progression. Results: Although individuals in the ADNI cohort were older (74.68 [5.65] vs. 65.38 [4.66], p < 0.001) and had higher educational levels (16.3 [2.6] vs. 12.6 [2.8], p < 0.001) than those in the SILCODE cohort, similar loadings between resilience and its indicators were found within both models. BR and GR were mainly associated with age, women, and brain volume in both cohorts. Prediction models showed that higher CR and GR were related to better cognitive performance, and specifically, all types of resilience to CSF Aβ could predict longitudinal cognitive decline. Conclusion: Different phenotypes of resilience depending on cognition and brain volumes were associated with different factors. Such comprehensive resilience provided insight into the mechanisms of susceptibility for Alzheimer's disease (AD) at the individual level, and interindividual differences in resilience had the potential to predict the disease progression in CN people.
| S-EPMC7943465 | biostudies-literature