Representativeness of samples enrolled in Alzheimer's disease research centers

Rentería, Miguel Arce; Mobley, Taylor M; Evangelista, Nicole D.; Medina, Luis D.; Deters, Kacie; Fox‐Fuller, Joshua T; Minto, Lex R; Avila‐Rieger, Justina; Bettcher, Brianne M.

doi:10.1002/dad2.12450

Cited by 15 publications

(11 citation statements)

References 60 publications

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“…NACC participants were noteworthy in having the second highest rates of incident dementia despite the lowest degrees of frailty (relative to other cohorts), aligning with the known issues of NACC representativeness relative to the broader United States population (e.g. fewer physical and mental health problems but more subjective cognitive complaints) 46 . The method of dementia detection employed in each study also varied substantially, from physician-derived diagnoses (MAP, NACC), to mostly self- and informant-report (ELSA), and to estimated classifications based on a combination of cognitive tests (HRS).…”

Section: Discussionmentioning

confidence: 59%

Frailty trajectories preceding dementia: an individual-level analysis of four cohort studies in the United States and United Kingdom

Ward,

Flint,

Littlejohns

et al. 2024

Preprint

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Frailty may represent a modifiable risk factor for dementia, but the direction of that association remains uncertain. We investigated frailty trajectories in the years preceding dementia onset using data from 23,672 participants (242,760 person-years of follow-up, 2,906 cases of incident dementia) across four cohort studies in the United States and United Kingdom. Bayesian non-linear models revealed accelerations in frailty trajectories 4–9 years before incident dementia. Among participants whose time between frailty measurement and incident dementia exceeded that prodromal period, frailty remained positively associated with dementia risk (adjusted hazard ratios ranged from 1.20 [95% confidence interval, CI = 1.15–1.26] to 1.43 [95% CI = 1.14–1.81]). This observational evidence suggests that frailty increases dementia risk independently of any reverse causality. These findings indicate that frailty measurements can be used to identify high-risk population groups for preferential enrolment into clinical trials for dementia prevention and treatment. Frailty itself may represent a useful upstream target for behavioural and societal approaches to dementia prevention.

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Section: Discussionmentioning

confidence: 59%

Frailty trajectories preceding dementia: an individual-level analysis of four cohort studies in the United States and United Kingdom

Ward,

Flint,

Littlejohns

et al. 2024

Preprint

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“…These participants tend to have a higher education and a greater proportion of white race than the US population. Both the sample collection and difference from the general population limits generalizability to the US population [ 18 ]. However, there are no studies of this size with such validated longitudinal data to study NPI and dementia staging’s associations with divorce or separation.…”

Section: Resultsmentioning

confidence: 99%

Associations between dementia staging, neuropsychiatric behavioral symptoms, and divorce or separation in late life: A case control study

et al. 2023

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Dementia can be difficult for married couples for many reasons, including the introduction of caregiving burden, loss of intimacy, and financial strain. In this study, we investigated the impact of dementia staging and neuropsychiatric behavioral symptoms on the likelihood of divorce or separation for older adult married couples. For this case-control study, we used data from the National Alzheimer’s Coordinating Center (NACC) Uniform dataset (UDS) versions 2 and 3. This dataset was from 2007 to 2021 and contains standardized clinical information submitted by NIA/NIH Alzheimer’s Disease Research Centers (ADRCs) across the United States (US). This data was from 37 ADRCs. We selected participants who were married or living as married/domestic partners at their initial visit. Cases were defined by a first divorce/separation occurring during the follow-up period, resulting in 291 participants. We selected 5 controls for each married/living as married case and matched on age. Conditional logistic regression estimated the association between overall Neuro Psychiatric Inventory (NPI) score and severity of individual symptoms of the NPI with case/control status, adjusted for education, the CDR® Dementia Staging Instrument score, living situation, symptom informant, sex, and race. Separate analyses were conducted for each symptom. Multiple comparisons were accounted for with the Hochberg method. Later stage of dementia was negatively associated with divorce/separation with an adjusted odds ratio (AOR) = 0.68 (95%CI = 0.50 to 0.93). A higher overall NPI score was positively associated with divorce/separation AOR = 1.08 (95% CI = 1.03 to 1.12,). More severe ratings of agitation/aggression, depression/dysphoria, disinhibition, and elation/euphoria were associated with greater odds of divorce/separation. Among older adults in the US, a later stage of dementia is associated with a lower likelihood of divorce or separation, while having more severe neuropsychiatric behavioral symptoms of agitation/aggression, depression/dysphoria, disinhibition, and elation/euphoria are associated with a higher likelihood of divorce or separation.

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“…Unfortunately, this underrepresentation has been a major public health problem across the AD field [210, 213–216], not just those utilizing EVs.…”

Section: Future Directions and Limitationsmentioning

confidence: 99%

Extracellular Vesicles for Alzheimer’s Disease and Dementia Diagnosis

Taha

2024

Preprint

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Accurate differential diagnosis of dementia disorders including Alzheimer’s disease (AD), frontotemporal dementia (FTD), dementia with Lewy bodies (DLB), Parkinson’s disease dementia (PDD), and vascular cognitive impairment and dementia (VCID), along with conditions like prodromal mild cognitive impairment (MCI) or negative controls (NCs), continues to challenge neurologists. The nuanced and sometimes shared pathophysiological features underscore the need for precision in developing disease-modifying therapies. In the pursuit of reliable antemortem biomarkers, extracellular vesicles (EVs) have emerged as a popular tool for their capacity to encapsulate disease-specific signatures, particularly in neurodegenerative and neurological disorders. To this end, we have performed a comprehensive, PRISMA-guided systematic review and meta-analysis, utilizing sophisticated statistical modeling to determine the diagnostic accuracy, explore between-study variance and heterogeneity (I2), and investigate potential publication bias using various statistical tests.Biomarkers derived from general EVs demonstrated superior diagnostic accuracy, less between-study variance, heterogeneity, and publication bias than those from speculative CNS-enriched EVs. The trim-and-fill method suggested a potential overestimation of diagnostic effectiveness for biomarkers derived from CNS-enriched EVs due to four hypothesized missing studies with low diagnostic results, but none for general EVs. Meta-regressions revealed that studies using cerebrospinal fluid or serum, involving non-fasting individuals, sampling in the afternoon, employing citrate instead of EDTA for blood collection, using thrombin for coagulation factor depletion, isolating EVs with purer methods such as combined ultracentrifugation and size-exclusion chromatography, not freezing EVs post-isolation, and quantifying miRNA biomarkers, achieved better diagnostic accuracy and less heterogeneity. The diagnostic accuracy was low in differentiating among different dementia disorders. However, the analysis for diagnosing persons with AD vs. VCID achieved the highest diagnostic accuracy, suggesting that further studies may focus on this comparison. Additionally, we highlight several limitations in the included studies and recommend the following: Implement the use of appropriate negative controls, thorough documentation of preanalytical factors, inclusion of more dementia groups beyond AD, comprehensive reporting on pharmacological treatments, consideration of racial and ethnic minority groups, adherence to ISEV guidelines, application of the A-T-N framework, detailed documentation of dementia stages, extension of studies beyond differential diagnosis, reanalysis when postmortem definitive diagnostics become available, evaluation of prodromal conversion rates, and commitment to accurate statistical modeling and data transparency. We hope that lessons learned from this comprehensive meta-analysis can be beneficial for those attempting to discover biomarkers for AD and related dementias through EVs or alternative approaches.

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Representativeness of samples enrolled in Alzheimer's disease research centers

Cited by 15 publications

References 60 publications

Frailty trajectories preceding dementia: an individual-level analysis of four cohort studies in the United States and United Kingdom

Frailty trajectories preceding dementia: an individual-level analysis of four cohort studies in the United States and United Kingdom

Associations between dementia staging, neuropsychiatric behavioral symptoms, and divorce or separation in late life: A case control study

Extracellular Vesicles for Alzheimer’s Disease and Dementia Diagnosis

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