Using subjective cognitive decline to identify high global amyloid in community-based samples: A cross-cohort study.
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ABSTRACT: Introduction
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.Methods
Three independent cohorts (890 clinically normal: 72 yrs ± 6.7; Female: 43.4%; SCD+: 24%; apolipoprotein E [APOE] ε4+: 28.5%; Aβ+: 32%) were used. SCD was dichotomized from one question. Using logistic regression, we classified Aβ+ using the SCD dichotomy, APOEε4, sex, and age.Results
SCD increased odds of Aβ+ by 1.58 relative to non-SCD. Female APOEε4 carriers with SCD exhibited higher odds of Aβ+ (OR = 3.34), whereas male carriers with SCD showed a weaker, opposing effect (OR = 0.37). SCD endorsement reduces the number of Aβ positron emission tomography scans to recruit Aβ+ individuals by 13% and by 9% if APOEε4 status is known.Conclusion
SCD helps to classify those with high Aβ, 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
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]
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Project description:ImportanceThe ability to explore associations between reports of subjective cognitive decline (SCD) and biomarkers of early Alzheimer disease (AD) pathophysiologic processes (accumulation of neocortical β-amyloid [Aβ] and tau) provides an important opportunity to understand the basis of SCD and AD risk.ObjectiveTo examine associations between SCD and global Aβ and tau burdens in regions of interest in clinically healthy older adults.Design, setting, and participantsThis 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 Aβ. 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 measuresSubjective 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 Aβ 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 Aβ, entorhinal cortical, and inferior temporal tau on SCD, controlling for age, sex, educational attainment, and Geriatric Depression Scale score.ResultsOf 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 Aβ burden. Greater SCD was associated with increasing entorhinal cortical tau burden (β = 0.35; 95% CI, 0.19-.52; P < .001) and Aβ burden (β = 0.24; 95% CI, 0.08-.40; P = .005), but not inferior temporal tau burden (β = 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 Aβ burden (β = 0.36; 95% CI, 0.15-.58; P = .001), and no interaction influenced SCD (β = -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 relevanceSubjective 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 Aβ. 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.
| S-EPMC5774633 | biostudies-literature
Project description:IntroductionThe evidence for characteristics of persons with subjective cognitive decline (SCD) associated with amyloid positivity is limited.MethodsIn 1640 persons with SCD from 20 Amyloid Biomarker Study cohort, we investigated the associations of SCD-specific characteristics (informant confirmation, domain-specific complaints, concerns, feelings of worse performance) demographics, setting, apolipoprotein E gene (APOE) ε4 carriership, and neuropsychiatric symptoms with amyloid positivity.ResultsBetween cohorts, amyloid positivity in 70-year-olds varied from 10% to 76%. Only older age, clinical setting, and APOE ε4 carriership showed univariate associations with increased amyloid positivity. After adjusting for these, lower education was also associated with increased amyloid positivity. Only within a research setting, informant-confirmed complaints, memory complaints, attention/concentration complaints, and no depressive symptoms were associated with increased amyloid positivity. Feelings of worse performance were associated with less amyloid positivity at younger ages and more at older ages.DiscussionNext to age, setting, and APOE ε4 carriership, SCD-specific characteristics may facilitate the identification of amyloid-positive individuals.
| S-EPMC9786747 | biostudies-literature
Project description:BackgroundWith the global population aging and life expectancy increasing, dementia has turned a priority in the health care system. In Chile, dementia is one of the most important causes of disability in the elderly and the most rapidly growing cause of death in the last 20 years. Cognitive complaint is considered a predictor for cognitive and functional decline, incident mild cognitive impairment, and incident dementia. The GERO cohort is the Chilean core clinical project of the Geroscience Center for Brain Health and Metabolism (GERO). The objective of the GERO cohort is to analyze the rate of functional decline and progression to clinical dementia and their associated risk factors in a community-dwelling elderly with subjective cognitive complaint, through a population-based study. We also aim to undertake clinical research on brain ageing and dementia disorders, to create data and biobanks with the appropriate infrastructure to conduct other studies and facilitate to the national and international scientific community access to the data and samples for research.MethodsThe GERO cohort aims the recruitment of 300 elderly subjects (> 70 years) from Santiago (Chile), following them up for at least 3 years. Eligible people are adults not diagnosed with dementia with subjective cognitive complaint, which are reported either by the participant, a proxy or both. Participants are identified through a household census. The protocol for evaluation is based on a multidimensional approach including socio-demographic, biomedical, psychosocial, neuropsychological, neuropsychiatric and motor assessments. Neuroimaging, blood and stool samples are also obtained. This multidimensional evaluation is carried out in a baseline and 2 follow-ups assessments, at 18 and 36 months. In addition, in months 6, 12, 24, and 30, a telephone interview is performed in order to keep contact with the participants and to assess general well-being.DiscussionOur work will allow us to determine multidimensional risks factors associated with functional decline and conversion to dementia in elderly with subjective cognitive complain. The aim of our GERO group is to establish the capacity to foster cutting edge and multidisciplinary research on aging in Chile including basic and clinical research.Trial registrationNCT04265482 in ClinicalTrials.gov. Registration Date: February 11, 2020. Retrospectively Registered.
| S-EPMC7690082 | biostudies-literature
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.
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Project description:ObjectiveTo assess in a longitudinal study whether subjective cognitive decline (SCD) and brain β-amyloid (Aβ) contribute unique information to cognitive decline.MethodsOne hundred thirty-six healthy elderly from the Berkeley Aging Cohort Study were followed up for a mean of 4 years. SCD and affective measures were generated from the Geriatric Depression Scale (GDS) with factor analysis on data from a larger set of 347 healthy, nondepressed (GDS <11) elderly individuals. Cognition was summarized with previously validated factor scores. Pittsburgh compound B (PiB)-PET scans were acquired to determine the presence (PiB+) or absence (PiB-) of Aβ pathology. Mixed models were used to assess the independent and interactive effects of SCD, affective features, PiB status, and time on cognition, with adjustment for demographic variables.ResultsSCD score demonstrated good construct validity compared to an existing measure of subjective memory and was partially explained by several lower-order measurements. Mixed models revealed that SCD interacted with PiB status to predict change in episodic memory and global cognition over time, with adjustment for affective features. PiB+ individuals with more severe SCD demonstrated the steepest cognitive decline. Worse SCD predicted faster decline in working memory independently of PiB status. No such effects were seen for affective scores when adjusted for SCD.ConclusionsPiB+ individuals with SCD are at greatest risk of cognitive decline. Evidence for amyloid alone is not sufficient to indicate risk of rapid cognitive decline in healthy elderly. Effects of GDS on cognitive decline in nondepressed cohorts may be driven by SCD rather than subsyndromal depression.
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Project description:Individuals with subjective cognitive decline (SCD) have the perception of memory problems without showing impairment on standardized cognitive tests. SCD has been associated with an increased risk of developing Alzheimer's disease (AD). Neuroticism and openness personality dimensions have also been associated with SCD and AD. From the aforementioned, we aimed to ascertain whether the dimensions and traits defined by the Zuckerman-Kuhlman Personality Questionnaire (ZKPQ) differentiate between individuals with SCD and the general population (GP). A total of 187 participants with SCD and mild affective symptomatology recruited from the Fundació ACE Health Brain Initiative (FACEHBI) project completed the ZKPQ. Each SCD participant was matched by sex and age to an individual from the GP. Both samples included 71 men and 116 women with a mean age of 65.9 years. Results indicated that the SCD group scored significantly lower in Neuroticism-Anxiety and Activity than the GP group. Only Activity remained statistically significant in a multivariate analysis. These findings suggest that individuals with SCD have a low energy level and a dislike for an active and busy life. From the obtained results and knowing additional physical activities may delay the conversion from normal aging to cognitive impairment, we encourage promoting this lifestyle in daily routine. The assessment of personality may result in an SCD plus feature, which may serve as an upgrading strategy for future research.
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Project description:IntroductionAmyloid pathology in cognitively normal adults is associated with subjective cognitive decline, potentially reflecting awareness of Alzheimer's-related memory deficits. To clarify the mechanism underlying this relationship, we used mediational analyses to determine the role of depression, anxiety, and actual memory performance.MethodsTo assess amyloid deposition, we imaged 85 cognitively normal adults with florbetapir positron emission tomography imaging. Subjective cognitive decline was measured using a multidimensional instrument that assessed seven subjective memory domains. Mediational measures included assessments of actual memory performance (current and retrospective longitudinal change), depression, and anxiety.ResultsThe relationship between amyloid and subjective cognitive decline was mediated by poorer memory performance and greater retrospective memory decline, not depression or anxiety. The mediational roles were significant for domains associated with memory function and memory-related anxiety.DiscussionIn individuals harboring amyloid, self-reported beliefs of declining memory likely indicate early self-awareness of actual worsening function rather than depression or anxiety.
| S-EPMC6376166 | biostudies-literature
Project description:IntroductionSubjective cognitive decline (SCD) may be an early symptomatic manifestation of Alzheimer's disease, though published research largely neglects how to classify SCD in community-based studies.MethodsIn neuropsychologically intact Einstein Aging Study participants (n = 1115; mean age = 78; 63% female; 30% non-White), we used Cox models to examine the association between self-perceived cognitive functioning at baseline (using three different approaches) and incident amnestic mild cognitive impairment (aMCI) with covariates of age, sex, education, race/ethnicity, general (objective) cognition, depressive symptoms, and four other SCD-related features.ResultsAfter a median of 3 years, 198 participants developed aMCI. In models that included all the variables, self-perceived cognitive functioning was consistently associated with incident aMCI as were age, general cognition, and perceived control; apolipoprotein E (APOE) ε4 allele status was significant in one model. We set cut points that optimized the diagnostic accuracy of SCD at various time frames.DiscussionWe provide an approach to SCD classification and discuss implications for cognitive aging studies.
| S-EPMC7521594 | biostudies-literature
Project description:As a potential preclinical stage of Alzheimer's dementia, subjective cognitive decline (SCD) reveals a higher risk of future cognitive decline and conversion to dementia. However, it has not been clear whether SCD status increases the clinical progression of older adults in the context of amyloid deposition, cerebrovascular disease (CeVD), and psychiatric symptoms. We identified 99 normal controls (NC), 15 SCD individuals who developed mild cognitive impairment in the next 2 years (P-SCD), and 54 SCD individuals who did not (S-SCD) from ADNI database with both baseline and 2-year follow-up data. Total white matter hyperintensity (WMH), WMH in deep (DWMH) and periventricular (PWMH) regions, and voxel-wise grey matter volumes were compared among groups. Furthermore, using structural equation modelling method, we constructed path models to explore SCD-related brain changes longitudinally and to determine whether baseline SCD status, age, and depressive symptoms affect participants' clinical outcomes. Both SCD groups showed higher baseline amyloid PET SUVR, baseline PWMH volumes, and larger increase of PWMH volumes over time than NC. In contrast, only P-SCD had higher baseline DWMH volumes and larger increase of DWMH volumes over time than NC. No longitudinal differences in grey matter volume and amyloid was observed among NC, S-SCD, and P-SCD. Our path models demonstrated that SCD status contributed to future WMH progression. Further, baseline SCD status increases the risk of future cognitive decline, mediated by PWMH; baseline depressive symptoms directly contribute to clinical outcomes. In conclusion, both S-SCD and P-SCD exhibited more severe CeVD than NC. The CeVD burden increase was more pronounced in P-SCD. In contrast with the direct association of depressive symptoms with dementia severity progression, the effects of SCD status on future cognitive decline may manifest via CeVD pathologies. Our work highlights the importance of multi-modal longitudinal designs in understanding the SCD trajectory heterogeneity, paving the way for stratification and early intervention in the preclinical stage. PRACTITIONER POINTS: Both S-SCD and P-SCD exhibited more severe CeVD at baseline and a larger increase of CeVD burden compared to NC, while the burden was more pronounced in P-SCD. Baseline SCD status increases the risk of future PWMH and DWMH volume accumulation, mediated by baseline PWMH and DWMH volumes, respectively. Baseline SCD status increases the risk of future cognitive decline, mediated by baseline PWMH, while baseline depression status directly contributes to clinical outcome.
| S-EPMC11220833 | biostudies-literature
Project description:Since late stage dementia, including Alzheimer's disease (AD), cannot be reversed by any available drugs, there is increasing research interest in the preclinical stage of AD, i.e., subjective cognitive decline (SCD). SCD is characterized by self-perceptive cognitive decline but is difficult to detect using objective tests. At SCD stage, the cognitive deficits can be more easily reversed compared to that of mild cognitive impairment (MCI) and AD only if accurate diagnosis of SCD and early intervention can be developed. In this paper, we review the recent progress of SCD research including current assessment tools, biomarkers, neuroimaging, intervention and expected prognosis, and the potential relevance to traumatic brain injury (TBI)-induced cognitive deficits.
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