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

ACCESS DATA

Publications

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

Similar Datasets

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:Subjective cognitive decline (SCD) as an indicator of preclinical Alzheimer's disease (AD) may precede mild cognitive impairment (MCI) over several decades. Self-reported cognitive decline as a typical clinical manifestation is critical in preclinical AD. Metacognition represents a person's ability to accurately assess cognition. Our study aimed to examine (1) the alternations of metamemory in a cohort across the Alzheimer's continuum, (2) the association between metamemory and cognition, and (3) the relationship of cortical thickness in four regions of interest (ROI) with metamemory scores. Six hundred ninety-seven participants were classified as 79 AD dementia, 161 aMCI, 261 SCD, and 196 cognitively unimpaired (CU) individuals, in which 418 participants aged above 65, 131 participants with Aβ+ after receiving positron emission tomography, and 602 participants received sMRI. The degree of confidence (DOC) was measured by calculating discrepancies between judgments and memory performance. We assessed the relationships between DOC tertiles and cognition and analyzed the screening power, then investigated the partial correlation between DOC and ROIs, controlled by age, sex, and cognition. In the Aβ+ subgroup, SCD showed significantly higher DOC scores than the CU group. There was an increasing trend of overconfidence with the decline of cognition across the AD spectrum (P for trend < 0.001). After adjusting for age, sex, and education, the lower degree of confidence-long-term delay recall (DOC-LD) tertiles were associated with lower odds ratio in SCD, aMCI, and AD in the Aβ+ subgroup (all P for trend < 0.05). The area under the curves of DOC scores for screening SCD from CU in the Aβ+ subgroup was better than that in all participants and the age ≥65 subgroup. Partial correlation showed that in the Aβ+ subgroup, DOC-SD (degree of confidence-short-term delay recall) was negatively correlated with the anterior cingulate cortex; DOC-LD was negatively correlated with the cortices of parahippocampal, anterior cingulate, posterior cingulate, and medial orbitofrontal. In individuals with Aβ+, SCD exhibited a detectable metamemory alternation before objective cognitive impairment could be tested, indicated by the overestimation in the memory performance. The pattern of an increasing trend of overconfidence across SCD, aMCI, and AD dementia supports the view of a continuum in Alzheimer's disease.

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

OmicsDI is part of the ELIXIR infrastructure

Tweets