Protocol of the Cognitive Health in Ageing Register: Investigational, Observational and Trial Studies in Dementia Research (CHARIOT): Prospective Readiness cOhort (PRO) SubStudy

Udeh-Momoh, Chinedu; Watermeyer, Tamlyn; Price, Geraint; Loots, Celeste A. de Jager; Reglińska-Matveyev, Natalia; Ropacki, Michael T.; Ketter, Nzeera; Fogle, Michael; Raghavan, Nandini; Arrighi, Michael; Brashear, Robert; Di, Jianing; Baker, Susan; Giannakopoulou, Parthenia; Robb, Catherine; Bassil, Darina; Cohn, Martin; McLellan-Young, Heather; Crispin, Jennifier; Lakey, Kristina; Curry, Lisa; Seemulamoodi, Yellappa Chowdary; Kafetsouli, Dimitra; Perera, Dinithi; Car, Josip; Majeed, Azeem; Ward, Heather; Ritchie, Karen; Perneczky, Robert; Kivipelto, Miia; Scott, David J.; Bracoud, Luc; Saad, Ziad S.; Novak, Gerald; Ritchie, Craig W.; Middleton, Lefkos T.

doi:10.1136/bmjopen-2020-043114

Cited by 3 publications

(8 citation statements)

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“…CHARIOT-PRO SubStudy is an on-going prospective cohort study of cognitively unimpaired older adults in the United Kingdom, which aims to examine longitudinal cognitive changes in those with and without brain amyloid-beta (Aβ42) pathology, and factors and markers of subsequent decline ( Udeh-Momoh et al, 2021 ). Following screening of 2425 individuals, including amyloid status determination and multiple cognitive tests, an equal number of participants above and below a binary threshold of Aβ42 positivity were enrolled at baseline and in subsequent longitudinal study.…”

Section: Methodsmentioning

confidence: 99%

“…During screening, participants whose performance on any RBANS index was poorer than 1.5 standard deviation (SD) below the population mean (population norms from Randolph, 1998 ) were referred to an adjudication panel of neurologists, psychiatrists and neuropsychologists to detect any undiagnosed cognitive impairment which was an exclusion criterion. The detailed inclusion/exclusion criteria and study procedures have been described in previous papers of our group ( Nalder et al, 2021 ; Udeh-Momoh et al, 2021 ). The study received approval from the National Research Ethics Service (NRES) Committee London Central [reference 15/LO/0711 (IRAS 140764)], as well as independent ethics review by committees from the local sites.…”

Section: Methodsmentioning

confidence: 99%

“…A total of 502 participants aged 60–85 years completed RBANS assessments in both screening and baseline clinic visits and were included in this study ( Udeh-Momoh et al, 2021 ). The median time gap between the screening visit and the baseline visit was 3.5 months, which allowed us to examine the practice effects in RBANS scale within a relatively short time period with less concern that the test-retest score differences are (partially) due to the cognitive decline during this time interval.…”

Section: Methodsmentioning

confidence: 99%

“…Three F18-radiolabeled amyloid tracers were used: florbetapir (Amyvid), flutemetamol (Vizamyl) and florbetaben (Neuraceq). The composite cortical SUVR threshold was 1.14 for Amyvid and 1.23 for Vizamyl (both with whole cerebellum as reference region), and 1.20 for Neuraceq (with cerebellar grey matter as reference region) ( Udeh-Momoh et al, 2021 ).…”

Section: Methodsmentioning

confidence: 99%

“…This study aimed to evaluate PE in the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) ( Randolph et al, 1998 ), and its associations with brain amyloid status and other factors in a cohort of cognitively unimpaired older adults in the United Kingdom Cognitive Health in Ageing Register: Investigational, Observational, and Trial Studies in Dementia Research: Prospective Readiness cOhort Study (CHARIOT-PRO) SubStudy ( Udeh-Momoh et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

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Practice Effect of Repeated Cognitive Tests Among Older Adults: Associations With Brain Amyloid Pathology and Other Influencing Factors

Zheng

Udeh-Momoh

Watermeyer

et al. 2022

Front. Aging Neurosci.

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BackgroundPractice effects (PE), after repeated cognitive measurements, may mask cognitive decline and represent a challenge in clinical and research settings. However, an attenuated practice effect may indicate the presence of brain pathologies. This study aimed to evaluate practice effects on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) scale, and their associations with brain amyloid status and other factors in a cohort of cognitively unimpaired older adults enrolled in the CHARIOT-PRO SubStudy.Materials and Methods502 cognitively unimpaired participants aged 60-85 years were assessed with RBANS in both screening and baseline clinic visits using alternate versions (median time gap of 3.5 months). We tested PE based on differences between test and retest scores in total scale and domain-specific indices. Multiple linear regressions were used to examine factors influencing PE, after adjusting for age, sex, education level, APOE-ε4 carriage and initial RBANS score. The latter and PE were also evaluated as predictors for amyloid positivity status based on defined thresholds, using logistic regression.ResultsParticipants’ total scale, immediate memory and delayed memory indices were significantly higher in the second test than in the initial test (Cohen’s dz = 0.48, 0.70 and 0.35, P < 0.001). On the immediate memory index, the PE was significantly lower in the amyloid positive group than the amyloid negative group (P = 0.022). Older participants (≥70 years), women, non-APOE-ε4 carriers, and those with worse initial RBANS test performance had larger PE. No associations were found between brain MRI parameters and PE. In addition, attenuated practice effects in immediate or delayed memory index were independent predictors for amyloid positivity (P < 0.05).ConclusionSignificant practice effects on RBANS total scale and memory indices were identified in cognitively unimpaired older adults. The association with amyloid status suggests that practice effects are not simply a source of measurement error but may be informative with regard to underlying neuropathology.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Practice Effect of Repeated Cognitive Tests Among Older Adults: Associations With Brain Amyloid Pathology and Other Influencing Factors

Zheng

Udeh-Momoh

Watermeyer

et al. 2022

Front. Aging Neurosci.

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A multi-omics approach identifies a blood-based miRNA signature of cognitive decline in two large observational trials

Sadlon

Takousis

Εvangelou

et al. 2022

Preprint

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Identifying individuals before the onset of overt symptoms is a key prerequisite for the prevention of Alzheimer's disease (AD). A wealth of data reports dysregulated microRNA (miRNA) expression in the blood of individuals with AD, but evidence in individuals at subclinical stages is sparse. In this study, a qPCR analysis of a prioritised set of 38 candidate miRNAs in the blood of 830 healthy individuals from the CHARIOT PRO cohort (West London, UK) was undertaken. Here, we identified six differentially expressed miRNAs (hsa-miR-128-3p, hsa-miR-144-5p, hsa-miR-146a-5p, hsa-miR-26a-5p, hsa-miR-29c-3p and hsa-miR-363-3p) in the blood of individuals with low cognitive performance on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). A pathway enrichment analysis for the six miRNAs indicated involvement of apoptosis and inflammation, relevant in early AD stages. Subsequently, we used whole genome sequencing (WGS) data from 750 individuals from the AD Neuroimaging Initiative (ADNI) to perform a genetic association analysis for polymorphisms within the significant miRNAs' genes and CSF concentrations of phosphorylated-tau, total-tau, amyloid-β42 and soluble-TREM2 and BACE1 activity. Our analysis revealed 24 SNPs within MIR29C to be associated with CSF levels of amyloid-β42 and soluble-TREM2 and BACE1 activity. Our study shows the potential of a six-miRNA set as diagnostic blood biomarker of subclinical cognitive deficits in AD. Polymorphisms within MIR29C suggest a possible interplay between the amyloid cascade and microglial activation at preclinical stages of AD.

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Remote data collection speech analysis in people at risk for Alzheimer's disease dementia: usability and acceptability results

Gregory,

Harrison,

Herrmann

et al. 2023

Front. Dement.

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IntroductionDigital cognitive assessments are gathering importance for the decentralized remote clinical trials of the future. Before including such assessments in clinical trials, they must be tested to confirm feasibility and acceptability with the intended participant group. This study presents usability and acceptability data from the Speech on the Phone Assessment (SPeAk) study.MethodsParticipants (N = 68, mean age 70.43 years, 52.9% male) provided demographic data and completed baseline and 3-month follow-up phone based assessments. The baseline visit was administered by a trained researcher and included a spontaneous speech assessment and a brief cognitive battery (immediate and delayed recall, digit span, and verbal fluency). The follow-up visit repeated the cognitive battery which was administered by an automatic phone bot. Participants were randomized to receive their cognitive test results acer the final or acer each study visit. Participants completed acceptability questionnaires electronically acer each study visit.ResultsThere was excellent retention (98.5%), few technical issues (n = 5), and good interrater reliability. Participants rated the assessment as acceptable, confirming the ease of use of the technology and their comfort in completing cognitive tasks on the phone. Participants generally reported feeling happy to receive the results of their cognitive tests, and this disclosure did not cause participants to feel worried.DiscussionThe results from this usability and acceptability analysis suggest that completing this brief battery of cognitive tests via a telephone call is both acceptable and feasible in a midlife-to-older adult population in the United Kingdom, living at risk for Alzheimer's disease.

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Protocol of the Cognitive Health in Ageing Register: Investigational, Observational and Trial Studies in Dementia Research (CHARIOT): Prospective Readiness cOhort (PRO) SubStudy

Cited by 3 publications

References 37 publications

Practice Effect of Repeated Cognitive Tests Among Older Adults: Associations With Brain Amyloid Pathology and Other Influencing Factors

Practice Effect of Repeated Cognitive Tests Among Older Adults: Associations With Brain Amyloid Pathology and Other Influencing Factors

A multi-omics approach identifies a blood-based miRNA signature of cognitive decline in two large observational trials

Remote data collection speech analysis in people at risk for Alzheimer's disease dementia: usability and acceptability results

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