Instrumental activities of daily living, amyloid, and cognition in cognitively normal older adults screening for the A4 Study

Marshall, Gad A.; Sikkes, Sietske A.M.; Amariglio, Rebecca E.; Gatchel, Jennifer R.; Rentz, Dorene M.; Johnson, Keith A.; Langford, Oliver; Sun, Chung-Kai; Donohue, Michael C.; Raman, Rema; Aisen, Paul S.; Sperling, Reisa A.; Galasko, Douglas; STUDY.org, site personnel available at A

doi:10.1002/dad2.12118

Cited by 19 publications

(19 citation statements)

References 39 publications

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“…When investigating participant- and study partner-report, a few findings stand out. First, several studies have found that there is no perfect concordance between participants and study partners, even in cognitively normal populations ( Farias et al, 2005 ; Okonkwo et al, 2008 ; Marshall et al, 2020 ). Factors such as participant education, depression, and anxiety, as well as the nature of the relationship and the frequency and intensity of contact between participants and study partners, may affect how either party reports impairments, leading to discordance where one may report more or fewer impairments than the other.…”

Section: Introductionmentioning

confidence: 99%

Everyday Functioning in a Community-Based Volunteer Population: Differences Between Participant- and Study Partner-Report

Verrijp

Dubbelman

Visser

et al. 2022

Front. Aging Neurosci.

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Introduction: Impaired awareness in dementia caused by Alzheimer’s disease and related disorders made study partner-report the preferred method of measuring interference in “instrumental activities of daily living” (IADL). However, with a shifting focus toward earlier disease stages and prevention, the question arises whether self-report might be equally or even more appropriate. The aim of this study was to investigate how participant- and study partner-report IADL perform in a community-based volunteer population without dementia and which factors relate to differences between participant- and study partner-report.Methods: Participants (N = 3,288; 18–97 years, 70.4% females) and their study partners (N = 1,213; 18–88 years, 45.8% females) were recruited from the Dutch Brain Research Registry. IADL were measured using the Amsterdam IADL Questionnaire. The concordance between participant- and study partner-reported IADL difficulties was examined using intraclass correlation coefficient (ICC). Multinomial logistic regressions were used to investigate which demographic, cognitive, and psychosocial factors related to participant and study partner differences, by looking at the over- and underreport of IADL difficulties by the participant, relative to their study partner.Results: Most A-IADL-Q scores represented no difficulties for both participants (87.9%) and study partners (89.4%). The concordance between participants and study partners was moderate (ICC = 0.55, 95% confidence interval [CI] = [0.51, 0.59]); 24.5% (N = 297) of participants overreported their IADL difficulties compared with study partners, and 17.8% (N = 216) underreported difficulties. The presence of depressive symptoms (odds ratio [OR] = 1.31, 95% CI = [1.12, 1.54]), as well as memory complaints (OR = 2.45, 95% CI = [1.80, 3.34]), increased the odds of participants overreporting their IADL difficulties. Higher IADL ratings decreased the odds of participant underreport (OR = 0.71, 95% CI = [0.67, 0.74]).Conclusion: In this sample of community-based volunteers, most participants and study partners reported no major IADL difficulties. Differences between participant and study partner were, however, quite prevalent, with subjective factors indicative of increased report of IADL difficulties by the participant in particular. These findings suggest that self- and study partner-report measures may not be interchangeable, and that the level of awareness needs to be considered, even in cognitively healthy individuals.

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Section: Introductionmentioning

confidence: 99%

Everyday Functioning in a Community-Based Volunteer Population: Differences Between Participant- and Study Partner-Report

Verrijp

Dubbelman

Visser

et al. 2022

Front. Aging Neurosci.

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“…Visual read paradigms to assign a scan as positive or negative have been developed for amyloid and more recently tau PET tracers and validated against neuropathology in autopsy studies [19][20][21]. While visual reads are sometimes used as the inclusion methodology in clinical trials, quantitative PET scan analysis criteria are also often used, either in conjunction with or instead of visual reads [22]. Most simply, a PET scan is summarized by a single global or representative derived number, which as a continuous variable can then be binarized with respect to a positivity threshold value.…”

Section: Confirmation Of Disease Biologymentioning

confidence: 99%

The Use, Standardization, and Interpretation of Brain Imaging Data in Clinical Trials of Neurodegenerative Disorders

Schwarz

2021

Neurotherapeutics

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Imaging biomarkers play a wide-ranging role in clinical trials for neurological disorders. This includes selecting the appropriate trial participants, establishing target engagement and mechanism-related pharmacodynamic effect, monitoring safety, and providing evidence of disease modification. In the early stages of clinical drug development, evidence of target engagement and/or downstream pharmacodynamic effect—especially with a clear relationship to dose—can provide confidence that the therapeutic candidate should be advanced to larger and more expensive trials, and can inform the selection of the dose(s) to be further tested, i.e., to “de-risk” the drug development program. In these later-phase trials, evidence that the therapeutic candidate is altering disease-related biomarkers can provide important evidence that the clinical benefit of the compound (if observed) is grounded in meaningful biological changes. The interpretation of disease-related imaging markers, and comparability across different trials and imaging tools, is greatly improved when standardized outcome measures are defined. This standardization should not impinge on scientific advances in the imaging tools per se but provides a common language in which the results generated by these tools are expressed. PET markers of pathological protein aggregates and structural imaging of brain atrophy are common disease-related elements across many neurological disorders. However, PET tracers for pathologies beyond amyloid β and tau are needed, and the interpretability of structural imaging can be enhanced by some simple considerations to guard against the possible confound of pseudo-atrophy. Learnings from much-studied conditions such as Alzheimer’s disease and multiple sclerosis will be beneficial as the field embraces rarer diseases.

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“…Existing studies [11,15,16,[32][33][34][35][36][37][38][39] have shown that several lifestyle factors, including alcohol, daily living activities, and cognitive activities, are closely linked to AD. In particular, research on the role of alcohol consumption in cognitive functions and dementia was conducted [15][16][17]; nonetheless, their findings were mixed or even contradicting.…”

Section: Discussionmentioning

confidence: 99%

Alcohol Intake Differentiates AD and LATE: A Telltale Lifestyle from Two Large-Scale Datasets

Peng

Nelson

et al. 2022

Preprint

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Alzheimer’s disease (AD), as a progressive brain disease, affects cognition, memory, and behavior. Similarly, limbic-predominant age-related TDP-43 encephalopathy (LATE) is a recently defined common neurodegenerative disease that mimics the clinical symptoms of AD. At present, the risk factors implicated in LATE and those distinguishing LATE from AD are largely unknown. We leveraged an integrated feature selection-based algorithmic approach, to identify important factors differentiating subjects with LATE and/or AD from Control on significantly imbalanced data. We analyzed two datasets ROSMAP and NACC and discovered that alcohol consumption was a top lifestyle and environmental factor linked with LATE and AD and their associations were differential. In particular, we identified a specific subpopulation consisting of APOE e4 carriers. We found that, for this subpopulation, light-to-moderate alcohol intake was a protective factor against both AD and LATE, but its protective role against AD appeared stronger than LATE. The codes for our algorithms are available at https://github.com/xinxingwu-uk/PFV.

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Instrumental activities of daily living, amyloid, and cognition in cognitively normal older adults screening for the A4 Study

Cited by 19 publications

References 39 publications

Everyday Functioning in a Community-Based Volunteer Population: Differences Between Participant- and Study Partner-Report

Everyday Functioning in a Community-Based Volunteer Population: Differences Between Participant- and Study Partner-Report

The Use, Standardization, and Interpretation of Brain Imaging Data in Clinical Trials of Neurodegenerative Disorders

Alcohol Intake Differentiates AD and LATE: A Telltale Lifestyle from Two Large-Scale Datasets

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