Dataset Information

Using subjective cognitive decline to identify high global amyloid in community-based samples: A cross-cohort study.

ABSTRACT: Introduction:We aimed to examine the contribution of subjective cognitive decline (SCD) to reduce the number of ?-amyloid (A?) positron emission tomography scans required for recruiting A?+ clinically normal individuals in clinical trials. Methods:Three independent cohorts (890 clinically normal: 72 yrs ± 6.7; Female: 43.4%; SCD+: 24%; apolipoprotein E [APOE] ?4+: 28.5%; A?+: 32%) were used. SCD was dichotomized from one question. Using logistic regression, we classified A?+ using the SCD dichotomy, APOE?4, sex, and age. Results:SCD increased odds of A?+ by 1.58 relative to non-SCD. Female APOE?4 carriers with SCD exhibited higher odds of A?+ (OR = 3.34), whereas male carriers with SCD showed a weaker, opposing effect (OR = 0.37). SCD endorsement reduces the number of A? positron emission tomography scans to recruit A?+ individuals by 13% and by 9% if APOE?4 status is known. Conclusion:SCD helps to classify those with high A?, even beyond the substantial effect of APOE genotype. Collecting SCD is a feasible method for targeting recruitment for those likely on the AD trajectory.

SUBMITTER: Buckley RF

PROVIDER: S-EPMC6816447 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Using subjective cognitive decline to identify high global amyloid in community-based samples: A cross-cohort study.

Buckley Rachel F RF Sikkes Sietske S Villemagne Victor L VL Mormino Elizabeth C EC Rabin Jennifer S JS Burnham Samantha S Papp Kathryn V KV Doré Vincent V Masters Colin L CL Properzi Michael J MJ Schultz Aaron P AP Johnson Keith A KA Rentz Dorene M DM Sperling Reisa A RA Amariglio Rebecca E RE

Alzheimer's & dementia (Amsterdam, Netherlands) 20190925

<h4>Introduction</h4>We aimed to examine the contribution of subjective cognitive decline (SCD) to reduce the number of β-amyloid (Aβ) positron emission tomography scans required for recruiting Aβ+ clinically normal individuals in clinical trials.<h4>Methods</h4>Three independent cohorts (890 clinically normal: 72 yrs ± 6.7; Female: 43.4%; SCD+: 24%; apolipoprotein E [<i>APOE</i>] ε4+: 28.5%; Aβ+: 32%) were used. SCD was dichotomized from one question. Using logistic regression, we classified Aβ ...[more]

PMID: 31673597

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Project description:Importance:The ability to explore associations between reports of subjective cognitive decline (SCD) and biomarkers of early Alzheimer disease (AD) pathophysiologic processes (accumulation of neocortical ?-amyloid [A?] and tau) provides an important opportunity to understand the basis of SCD and AD risk. Objective:To examine associations between SCD and global A? and tau burdens in regions of interest in clinically healthy older adults. Design, Setting, and Participants:This imaging substudy of the Harvard Aging Brain Study included 133 clinically healthy older participants (Clinical Dementia Rating Scale global scores of 0) participating in the Harvard Aging Brain Study who underwent cross-sectional flortaucipir F 18 (previously known as AV 1451, T807) positron emission tomography (FTP-PET) imaging for tau and Pittsburgh compound B carbon 11-labeled PET (PiB-PET) imaging for A?. The following 2 regions for tau burden were identified: the entorhinal cortex, which exhibits early signs of tauopathy, and the inferior temporal region, which is more closely associated with AD-related pathologic mechanisms. Data were collected from June 11, 2012, through April 7, 2016. Main Outcomes and Measures:Subjective cognitive decline was measured using a previously published method of z-transforming subscales from the Memory Functioning Questionnaire, the Everyday Cognition battery, and a 7-item questionnaire. The A? level was measured according to a summary distribution volume ratio of frontal, lateral temporal and parietal, and retrosplenial PiB-PET tracer uptake. The FTP-PET measures were computed as standardized uptake value ratios. Linear regression models focused on main and interactive effects of A?, entorhinal cortical, and inferior temporal tau on SCD, controlling for age, sex, educational attainment, and Geriatric Depression Scale score. Results:Of the 133 participants, 75 (56.3%) were women and 58 (43.6%) were men; mean (SD) age was 76 (6.9) years (range, 55-90 years). Thirty-nine participants (29.3%) exhibited a high A? burden. Greater SCD was associated with increasing entorhinal cortical tau burden (??=?0.35; 95% CI, 0.19-.52; P?<?.001) and A? burden (??=?0.24; 95% CI, 0.08-.40; P?=?.005), but not inferior temporal tau burden (??=?0.10; 95% CI, -0.08 to 0.28; P?=?.27). This association between entorhinal cortical tau burden and SCD was largely unchanged after accounting for A? burden (??=?0.36; 95% CI, 0.15-.58; P?=?.001), and no interaction influenced SCD (??=?-0.36; 95% CI, -0.34 to 0.09; P?=?.25). An exploratory post hoc whole-brain analysis also indicated that SCD was predominantly associated with greater tau burden in the entorhinal cortex. Conclusions and Relevance:Subjective cognitive decline is indicative of accumulation of early tauopathy in the medial temporal lobe, specifically in the entorhinal cortex, and to a lesser extent, elevated global levels of A?. Our findings suggest multiple underlying pathways that motivate SCD that do not necessarily interact to influence SCD endorsement. As such, multiple biological factors must be considered when assessing SCD in clinically healthy older adults.

Project description:BackgroundSubjective cognitive decline (SCD) has been proposed as a pre-MCI at-risk condition of Alzheimer's disease (AD). Current research is focusing on a refined assessment of specific SCD features associated with increased risk for AD, as proposed in the SCD-plus criteria. We developed a structured interview (SCD-I) for the assessment of these features and tested their relationship with AD biomarkers.MethodsWe analyzed data of 205 cognitively normal participants of the DELCODE study (mean age = 68.9 years; 52% female) with available CSF AD biomarkers (Aß-42, p-Tau181, Aß-42/Tau ratio, total Tau). For each of five cognitive domains (including memory, language, attention, planning, others), a study physician asked participants about the following SCD-plus features: the presence of subjective decline, associated worries, onset of SCD, feeling of worse performance than others of the same age group, and informant confirmation. We compared AD biomarkers of subjects endorsing each of these questions with those who did not, controlling for age. SCD was also quantified by two summary scores: the number of fulfilled SCD-plus features, and the number of domains with experienced decline. Covariate-adjusted linear regression analyses were used to test whether these SCD scores predicted abnormality in AD biomarkers.ResultsLower Aß-42 levels were associated with a reported decline in memory and language abilities, and with the following SCD-plus features: onset of subjective decline within 5 years, confirmation of cognitive decline by an informant, and decline-related worries. Furthermore, both quantitative SCD scores were associated with lower Aß42 and lower Aß42/Tau ratio, but not with total Tau or p-Tau181.ConclusionsFindings support the usefulness of a criterion-based interview approach to assess and quantify SCD in the context of AD and validate the current SCD-plus features as predictors of AD pathology. While some features seem to be more closely associated with AD biomarkers than others, aggregated scores over several SCD-plus features or SCD domains may be the best predictors of AD pathology.

Dataset Information

Using subjective cognitive decline to identify high global amyloid in community-based samples: A cross-cohort study.

Publications

Using subjective cognitive decline to identify high global amyloid in community-based samples: A cross-cohort study.

Similar Datasets

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