Abstract
Background
Preclinical Alzheimer’s disease (AD) is determined by biomarker risk assessment in cognitively normal individuals. Disclosure of risk is usually required for clinical drug trials ...targeting specific biomarkers (e.g., beta‐amyloid). More broadly, there is a growing movement towards participant engagement, which has fostered an interest in biomarker disclosure. Apolipoprotein‐E (APOE) genotype disclosure has been well researched, but less is known about dual disclosure of APOE and amyloid PET. Better understanding of how individuals and their families react to AD risk information will help refine the disclosure protocol.
Method
Qualitative interviews were completed with 15 individuals (aged 61‐73) and 10 study partners who received APOE (all e4 carriers) and amyloid PET (5 positive) results as part of clinical trial screening. Interview transcripts were coded for motivation to learn, result comprehension, emotional/behavioral impact, and decision to share results. Analysis aims to characterize APOE vs. PET disclosure experiences between participants and partners.
Result
Motivation included altruism, worries about developing AD, and access to new information and treatment. Amyloid PET was viewed as a natural follow‐up to APOE genotyping or part of a comprehensive risk assessment, not a distinct test. Interestingly, most participants had already decided to learn about APOE and amyloid PET before informing their spouses, and in the case that their spouses disagreed, invited friends as study partners. Participants and partners consistently comprehended APOE as a remote risk factor and amyloid PET as more reflective of imminent AD pathology. However, those with negative PET understood that amyloid levels change over time, questioned how close they were to the threshold, and hoped for a repeat evaluation in the future. Most partners remembered the APOE disclosure more vividly than PET. Participants reported no change in memory complaints or worries about future decline regardless of risk level. Spouses rarely expressed concerns about the participant’s memory, were generally less worried about the results, and none observed memory changes after learning the risk level.
Conclusion
Dual disclosure of APOE and amyloid PET appears to have minimal impact on perception of memory. Participants generally had stronger reactions to amyloid PET, while spouses had more vivid experience with APOE.
Background
Subjective cognitive decline is an important factor in understanding AD risk and the progression of preclinical AD. Recent efforts have formalized a framework for defining and researching ...SCD, but significant variability still exists in the assessment and quantification of SCD (Jessen et al., 2014; Molinuevo et al., 2017). Including a uniform assessment of core defining SCD features in AD clinical research could help to overcome this problem and generalize research findings. We report preliminary data validating the novel Subjective Cognitive Decline Screen (SCDS), a 4‐item scale designed to assess key features of SCD in preclinical AD, as described by the Subjective Cognitive Decline Initiative (SCD‐I) Working Group.
Method
Participants were 97 cognitively unimpaired adults (ages 55‐80, 68% female, 93% White) pooled across two ongoing observational AD studies. The SCDS consists of 4 self‐report multiple choice questions assessing concerns about memory (0‐2 points), extent of memory decline (0‐2 points), and perceived memory change relative to peers (0‐1 point), with total scores ranging from 0 (no SCD) to 5 (high SCD).
Result
A total of 67% of participants endorsed at least one SCDS item. Total scores ranged from 0 to 5 (M = 1.3, SD = 1.4) and did not vary significantly on the basis of sex, age, or education. The SCDS demonstrated fairly high internal consistency overall (4 items; Cronbach’s α = .79), with an average inter‐item correlation of r = .48. The scale was positively correlated with the self‐report form of the Cognitive Function Index (CFI; Amariglio et al., 2015), a 14‐item measure of SCD widely used in AD research (r = .68, p < .01). In sub‐analyses of participants with known APOE genotype (n = 46) and known amyloid PET status (n= 25), SCDS scores did not differentiate APOE e4 carrier or amyloid PET status, respectively.
Conclusion
Our initial evidence suggests that the SCDS is a convenient tool for brief SCD assessment with fairly high internal consistency, though the average inter‐item correlation suggests some overlap in item content. Further work is needed to validate the scale in more racially and culturally diverse samples and in individuals with biomarker defined preclinical AD.
Objective: Dementia is a devastating neurological disease that may be better managed if diagnosed earlier when subclinical neurodegenerative changes are already present, including subtle cognitive ...decline and mild cognitive impairment. In this study, we used item-level performance on the Montreal Cognitive Assessment (MoCA) to identify individuals with subtle cognitive decline. Method: Individual MoCA item data from the Alzheimer's Disease Neuroimaging Initiative was grouped using k-modes cluster analysis. These clusters were validated and examined for association with convergent neuropsychological tests. The clusters were then compared and characterized using multinomial logistic regression. Results: A three-cluster solution had 77.3% precision, with Cluster 1 (high performing) displaying no deficits in performance, Cluster 2 (memory deficits) displaying lower memory performance, and Cluster 3 (compound deficits) displaying lower performance on memory and executive function. Age at MoCA (older in compound deficits), gender (more females in memory deficits), and marital status (fewer married in compound deficits) were significantly different among clusters. Age was not associated with increased odds of membership in the high-performing cluster compared to the others. Conclusions: We identified three clusters of individuals classified as cognitively unimpaired using cluster analysis. Individuals in the compound deficits cluster performed lower on the MoCA and were older and less often married than individuals in other clusters. Demographic analyses suggest that cluster identity was due to a combination of both cognitive and clinical factors. Identifying individuals at risk for future cognitive decline using the MoCA could help them receive earlier evidence-based interventions to slow further cognitive decline.
Key Points
Question: This study investigated a heterogenous group of individuals classified as cognitively unimpaired via cluster analysis of individual-item Montreal Cognitive Assessment (MoCA) performance. Findings: Individuals were organized into three clusters with 77.3% precision; the lowest performing cluster was characterized by lower scores on memory and executive function items, older age, and less common married status. Importance: This study sorted individuals categorized as cognitively unimpaired into three distinct clusters according to an easy-to-administer global cognitive test, thus providing a basis for clinicians to quickly and cost-effectively assess their patients' risk for future cognitive decline. Next Steps: Future research should focus on the neurodegenerative correlates of cluster membership, including amyloid-β deposition and cortical atrophy.
Background
Existing cognitive screening measures fall short in capturing preclinical AD, and cognitive impairment is unrecognized or misdiagnosed in 27‐81% of older adult primary care patients. ...Digital assessment technology has the potential to deliver more efficient and sensitive cognitive screening, but requires rigorous validation first. We aimed to determine the accuracy of remote (M2C2 mobile app) and clinic‐based (TabCAT and DCTclockTM) digital tests to distinguish between older adults with and without AD pathologic change. We used the Montreal Cognitive Assessment (MoCA) as a reference standard comparison test.
Method
We recruited 73 cognitively normal participants with Aß PET status (Aß+, n = 25; Aß‐, n = 48, determined by clinical read) from the Butler Hospital Alzheimer’s Prevention Registry (mean age = 69.2 and education = 16.5; 71% female; 89% White). Participants completed M2C2 tasks at home 3 times per day for 8 days, followed by the TabCAT tasks, DCTclockTM, and MoCA at an in‐person study visit. We calculated the area under the curve (AUC) to compare cognitive task accuracy to distinguish Aß status. Multi‐day learning curves were used to examine differences in M2C2 task performance by Aß status over time.
Result
Among the M2C2 tasks, average performance on the Prices task (episodic memory) over 8 days showed the highest accuracy (AUC = .77) to distinguish Aß status. The Aß+ group tended to perform worse than the Aß‐ group on the Prices task over time (Figure 1). On in‐person screening measures (single time‐point), accuracy to distinguish Aß was greatest for the TabCAT Favorites task (AUC = .76), relative to the DCTclockTM (AUC = .72) and the MoCA (AUC = .71).
Conclusion
We showed that several brief digital screening approaches (memory‐specific tasks on the M2C2 and TabCAT) outperform the MoCA in distinguishing between cognitively healthy individuals with and without elevated cerebral Aβ. Although further validation in community and clinic‐based samples is needed, these results suggest that these digital cognitive assessments may be suitable for more widespread screening to detect early pathological changes in neurodegenerative disorders. Figure 1. M2C2 task performance over time (3 sessions daily for 8 days) by Aβ status.
Abstract
Background
Existing cognitive screening measures fall short in capturing preclinical AD, and cognitive impairment is unrecognized or misdiagnosed in 27‐81% of older adult primary care ...patients. Digital assessment technology has the potential to deliver more efficient and sensitive cognitive screening, but requires rigorous validation first. We aimed to determine the accuracy of remote (M2C2 mobile app) and clinic‐based (TabCAT and DCTclock
TM
) digital tests to distinguish between older adults with and without AD pathologic change. We used the Montreal Cognitive Assessment (MoCA) as a reference standard comparison test.
Methods
We recruited 73 cognitively normal participants with Aß PET status (Aß+, n = 25; Aß‐, n = 48, determined by clinical read) from the Butler Hospital Alzheimer’s Prevention Registry (mean age = 69.2 and education = 16.5; 71% female; 89% White). Participants completed M2C2 tasks at home 3 times per day for 8 days, followed by the TabCAT tasks, DCTclock
TM
, and MoCA at an in‐person study visit. We calculated the area under the curve (AUC) to compare cognitive task accuracy to distinguish Aß status. Multi‐day learning curves were used to examine differences in M2C2 task performance by Aß status over time.
Results
Among the M2C2 tasks, average performance on the Prices task (episodic memory) over 8 days showed the highest accuracy (AUC = .77) to distinguish Aß status. The Aß+ group tended to perform worse than the Aß‐ group on the Prices task over time (Figure 1). On in‐person screening measures (single time‐point), accuracy to distinguish Aß was greatest for the TabCAT Favorites task (AUC = .76), relative to the DCTclock
TM
(AUC = .72) and the MoCA (AUC = .71).
Conclusions
We showed that several brief digital screening approaches (memory‐specific tasks on the M2C2 and TabCAT) outperform the MoCA in distinguishing between cognitively healthy individuals with and without elevated cerebral Aβ. Although further validation in community and clinic‐based samples is needed, these results suggest that these digital cognitive assessments may be suitable for more widespread screening to detect early pathological changes in neurodegenerative disorders.
Figure 1
. M2C2 task performance over time (3 sessions daily for 8 days) by Aβ status.
Background
The development of widely accessible, minimally invasive, cost‐effective Alzheimer’s disease (AD) biomarkers is a global public health imperative. There is a definite need for a ...multi‐stage neurodiagnostic screening system that is sensitive and specific to identify high risk individuals prior to cognitive decline. There is rapidly growing evidence that retinal biomarkers have the potential to serve as diagnostic or prognostic AD biomarkers. However, some results have been discordant due to variations in methodology, equipment, and study populations. Moreover, longitudinal data is sparse, and there is lack of insight as to which retinal biomarkers are relevant for each disease stage. Finally, the field needs to understand how structural, functional/metabolic, and angiographic retinal biomarkers interact in the AD process, and whether or not these interactions reflect cerebral pathophysiology. We propose a multi‐site longitudinal, prospective, observational study evaluating the natural history of retinal imaging biomarkers associated with AD disease risk, disease burden, and disease progression. The study objective is to create a ‘gold standard’ reference database of structural anatomic and functional imaging of the retina, in order to enable the identification and development of both sensitive and reliable markers of disease risk and/or disease progression.
Method
Participants (N=330 aged 55‐80; 50 CN– low AD risk, 200 CN – high AD risk, 50 MCI, and 30 mild AD) will be examined 4 times over 5 years. Exams will include neuropsychological testing, blood draw, APOE E4 genotyping, medical/functional assessment, gait assessment, and sleep analysis for 14 days post‐visit. Retinal OCT and OCT‐A will be completed on the Heidelberg SPECTRALIS II. Pupillometry and contrast sensitivity measures will be collected at each visit.
Result
We aim to use these data to develop a multivariate screening tool with sufficient sensitivity and specificity for identifying and tracking AD severity, including the preclinical stage of the disease.
Conclusion
Longitudinal study of structural, functional, metabolic, and angiographic retinal AD biomarkers in a large cohort could provide the foundation for the development of early stage screening biomarkers that can be applied by point‐of‐care clinicians. Our reference database will be open access, so that researchers worldwide can use these data to develop retinal AD biomarkers.
Abstract
Background
The development of widely accessible, minimally invasive, cost‐effective Alzheimer’s disease (AD) biomarkers is a global public health imperative. There is a definite need for a ...multi‐stage neurodiagnostic screening system that is sensitive and specific to identify high risk individuals prior to cognitive decline. There is rapidly growing evidence that retinal biomarkers have the potential to serve as diagnostic or prognostic AD biomarkers. However, some results have been discordant due to variations in methodology, equipment, and study populations. Moreover, longitudinal data is sparse, and there is lack of insight as to which retinal biomarkers are relevant for each disease stage. Finally, the field needs to understand how structural, functional/metabolic, and angiographic retinal biomarkers interact in the AD process, and whether or not these interactions reflect cerebral pathophysiology. We propose a multi‐site longitudinal, prospective, observational study evaluating the natural history of retinal imaging biomarkers associated with AD disease risk, disease burden, and disease progression. The study objective is to create a ‘gold standard’ reference database of structural anatomic and functional imaging of the retina, in order to enable the identification and development of both sensitive and reliable markers of disease risk and/or disease progression.
Method
Participants (N=330 aged 55‐80; 50 CN– low AD risk, 200 CN – high AD risk, 50 MCI, and 30 mild AD) will be examined 4 times over 5 years. Exams will include neuropsychological testing, blood draw, APOE E4 genotyping, medical/functional assessment, gait assessment, and sleep analysis for 14 days post‐visit. Retinal OCT and OCT‐A will be completed on the Heidelberg SPECTRALIS II. Pupillometry and contrast sensitivity measures will be collected at each visit.
Result
We aim to use these data to develop a multivariate screening tool with sufficient sensitivity and specificity for identifying and tracking AD severity, including the preclinical stage of the disease.
Conclusion
Longitudinal study of structural, functional, metabolic, and angiographic retinal AD biomarkers in a large cohort could provide the foundation for the development of early stage screening biomarkers that can be applied by point‐of‐care clinicians. Our reference database will be open access, so that researchers worldwide can use these data to develop retinal AD biomarkers.
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