Characteristics of subjective cognitive decline associated with amyloid positivity.
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ABSTRACT: Introduction
The evidence for characteristics of persons with subjective cognitive decline (SCD) associated with amyloid positivity is limited.Methods
In 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.Results
Between 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.Discussion
Next to age, setting, and APOE ε4 carriership, SCD-specific characteristics may facilitate the identification of amyloid-positive individuals.
SUBMITTER: Janssen O
PROVIDER: S-EPMC9786747 | biostudies-literature | 2022 Oct
REPOSITORIES: biostudies-literature
Publications
Characteristics of subjective cognitive decline associated with amyloid positivity.
Janssen Olin O Jansen Willemijn J WJ Vos Stephanie J B SJB Boada Merce M Parnetti Lucilla L Gabryelewicz Tomasz T Fladby Tormod T Molinuevo José Luis JL Villeneuve Sylvia S Hort Jakub J Epelbaum Stéphane S Lleó Alberto A Engelborghs Sebastiaan S van der Flier Wiesje M WM Landau Susan S Popp Julius J Wallin Anders A Scheltens Philip P Rikkert Marcel Olde MO Snyder Peter J PJ Rowe Chris C Chételat Gaël G Ruíz Agustin A Marquié Marta M Chipi Elena E Wolfsgruber Steffen S Heneka Michael M Boecker Henning H Peters Oliver O Jarholm Jonas J Rami Lorena L Tort-Merino Adrià A Binette Alexa Pichet AP Poirier Judes J Rosa-Neto Pedro P Cerman Jiri J Dubois Bruno B Teichmann Marc M Alcolea Daniel D Fortea Juan J Sánchez-Saudinós M Belén MB Ebenau Jarith J Pocnet Cornelia C Eckerström Marie M Thompson Louisa L Villemagne Victor V Buckley Rachel R Burnham Samantha S Delarue Marion M Freund-Levi Yvonne Y Wallin Åsa K ÅK Ramakers Inez I Tsolaki Magda M Soininen Hilkka H Hampel Harald H Spiru Luiza L Tijms Betty B Ossenkoppele Rik R Verhey Frans R J FRJ Jessen Frank F Visser Pieter Jelle PJ
Alzheimer's & dementia : the journal of the Alzheimer's Association 20211208 10
<h4>Introduction</h4>The evidence for characteristics of persons with subjective cognitive decline (SCD) associated with amyloid positivity is limited.<h4>Methods</h4>In 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 amyloi ...[more]
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Project description:BackgroundStage 1 of the National Institute on Aging-Alzheimer's Association's proposed Alzheimer's disease continuum is defined as amyloid-β (Aβ) positive but cognitively normal. Identifying at-risk individuals before Aβ reaches pathological levels could have great benefits for early intervention. Although Aβ levels become abnormal long before severe cognitive impairments appear, increasing evidence suggests that subtle cognitive changes may begin early, potentially before Aβ surpasses the threshold for abnormality. We examined whether baseline cognitive performance would predict progression from normal to abnormal levels of Aβ.MethodsWe examined the association of baseline cognitive composites (Preclinical Alzheimer Cognitive Composite, Alzheimer's Disease Neuroimaging Initiative (ADNI) memory factor composite) with progression to Aβ positivity in 292 nondemented, Aβ-negative ADNI participants. Additional analyses included continuous cerebrospinal fluid biomarker levels to examine the effects of subthreshold pathology.ResultsForty participants progressed to Aβ positivity during follow-up. Poorer baseline performance on both cognitive measures was significantly associated with increased odds of progression. More abnormal levels of baseline cerebrospinal fluid phosphorylated tau and subthreshold Aβ were associated with increased odds of progression to Aβ positivity. Nevertheless, baseline ADNI memory factor composite performance predicted progression even after controlling for baseline biomarker levels and APOE genotype (Preclinical Alzheimer Cognitive Composite was trend level). Survival analyses were largely consistent: controlling for baseline biomarker levels, baseline Preclinical Alzheimer Cognitive Composite still significantly predicted progression time to Aβ positivity (ADNI memory factor composite was trend level).ConclusionsThe possibility of intervening before Aβ reaches pathological levels is of obvious benefit. Low-cost, noninvasive cognitive measures can be informative for determining who is likely to progress to Aβ positivity, even after accounting for baseline subthreshold biomarker levels.
| S-EPMC7166153 | biostudies-literature
Project description:The importance of early interventions in Alzheimer's disease (AD) emphasizes the need to accurately and efficiently identify at-risk individuals. Although many dementia prediction models have been developed, there are fewer studies focusing on detection of brain pathology. We developed a model for identification of amyloid-PET positivity using data on demographics, vascular factors, cognition, APOE genotype, and structural MRI, including regional brain volumes, cortical thickness and a visual medial temporal lobe atrophy (MTA) rating. We also analyzed the relative importance of different factors when added to the overall model. The model used baseline data from the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) exploratory PET sub-study. Participants were at risk for dementia, but without dementia or cognitive impairment. Their mean age was 71 years. Participants underwent a brain 3T MRI and PiB-PET imaging. PiB images were visually determined as positive or negative. Cognition was measured using a modified version of the Neuropsychological Test Battery. Body mass index (BMI) and hypertension were used as cardiovascular risk factors in the model. Demographic factors included age, gender and years of education. The model was built using the Disease State Index (DSI) machine learning algorithm. Of the 48 participants, 20 (42%) were rated as Aβ positive. Compared with the Aβ negative group, the Aβ positive group had a higher proportion of APOE ε4 carriers (53 vs. 14%), lower executive functioning, lower brain volumes, and higher visual MTA rating. AUC [95% CI] for the complete model was 0.78 [0.65-0.91]. MRI was the most effective factor, especially brain volumes and visual MTA rating but not cortical thickness. APOE was nearly as effective as MRI in improving detection of amyloid positivity. The model with the best performance (AUC 0.82 [0.71-0.93]) was achieved by combining APOE and MRI. Our findings suggest that combining demographic data, vascular risk factors, cognitive performance, APOE genotype, and brain MRI measures can help identify Aβ positivity. Detecting amyloid positivity could reduce invasive and costly assessments during the screening process in clinical trials.
| S-EPMC7406705 | 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.
| S-EPMC9640736 | biostudies-literature
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.
| S-EPMC5679415 | biostudies-literature
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.
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Project description:BackgroundSince SCD (plus) was standardized, little is known about its demographic characteristics and its outcomes of neuropsychological assessments, including the SCD questionnaire 9 (SCD-Q9).ObjectiveTo characterize SCD (plus) by comparing the neuropsychological features among its subgroups and with normal controls (NC). Also, to explore its demographics and to understand the relation of the chief complaints and the scores of SCD-Q9.MethodsMultistage stratified cluster random sampling was conducted to select participants. As a result, 84 NC and 517 SCD (plus) were included. SCD (plus) was further classified into several subgroups (SCD-C: concerned cognitive decline; SCD-F: complaints about SCD within the past five years; SCD-P: feeling performance being not as good as their peers; SCD+: presented> 3 of SCD (plus) features; SCD-: presented ≤ 3 of SCD (plus) features (see the diagnostic criteria for the details)) and between-group comparisons of neuropsychological scores were conducted. Point-biserial correlation and binary logistic regression analyses were performed to investigate the demographic characteristics of its subgroups. Finally, Spearman correlation was used to better understand the relation of SCD (plus) to SCD-Q9.Results(1) Scores of AVLT-LR (AVLT-LR: Auditory Verbal Learning Test-Long Delayed Recall) and MoCA-B (MoCA: Montreal Cognitive Assessment-Basic) were lower in the SCD-P group than those in the NC group, and the SCD+ group scored lower in the MoCA-B and CDT(CDT: Clock Drawing Test) than the SCD- group. (2) Females were more concerned than male participants. Individuals with lower education level felt that their cognitive performance were worse than their peers. Also, younger people might express concerns more than the more elderly. People who had complaints of SCD-P might be more likely to report SCD-C, but less likely to report SCD-F. (3) Positive correlations were found between the chief complaints of SCD (plus) and some items of SCD-Q9.ConclusionsSCD (plus) may be related to demographic factors. Individuals with SCD (plus) already exhibited cognitive impairment, which can be detected by SCD-Q9.
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Project description:ObjectivesSubjective cognitive decline (SCD) is a known risk factor for Alzheimer's disease. However, little research has examined whether healthy older adults with SCD (SCD+) exhibit lower cognition and increased rates of cognitive decline compared to those without SCD (SCD-). The goal of this study was to examine if cognitive change over a 15-year period differs between SCD+ and SCD-.Method3,019 cognitively normal older adults (831 SCD+) from 3 Rush Alzheimer's Disease Center cohort studies were followed annually for up to a maximum of 15 years. Due to attrition, the average follow-up time was 5.7 years. Cognition was measured using z-scores of global cognition, episodic memory, semantic memory, perceptual speed, visuospatial ability, and working memory. Linear mixed-effects models investigated whether SCD was associated with cognitive change.ResultsBoth baseline cognition and cognitive change over time differed between SCD+ and SCD-. People with SCD+ exhibited lower baseline scores and a steeper decline in global cognition, episodic memory, semantic memory, and perceptual speed. People with SCD+ did not differ from SCD- in baseline visuospatial ability or working memory but exhibited increased change over time in those two domains compared to SCD-.DiscussionThe observed results reveal that older adults with SCD+ have lower baseline cognition and steeper declines in cognition over time compared to SCD-. Older adults with SCD may be aware of subtle cognitive declines that occur over time in global cognition, episodic memory, semantic memory, perceptual speed, visuospatial ability, and working memory compared to those without SCD.
| S-EPMC10066741 | 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.
| S-EPMC7248257 | biostudies-literature
Project description:Background: Accumulating evidence has demonstrated that plasma β-amyloid (Aβ) levels are useful biomarkers to reflect brain amyloidosis and gray matter structure, but little is known about their correlation with subclinical white matter (WM) integrity in individuals at risk of Alzheimer's disease (AD). Here, we investigated the microstructural changes in WM between subjects with low and high plasma Aβ levels among individuals with subjective cognitive decline (SCD). Methods: This study included 142 cognitively normal individuals with SCD who underwent a battery of neuropsychological tests, plasma Aβ measurements, and diffusion tensor imaging (DTI) based on the Sino Longitudinal Study on Cognitive Decline (SILCODE). Using tract-based spatial statistics (TBSS), we compared fractional anisotropy (FA), and mean diffusivity (MD) in WM between subjects with low (N = 71) and high (N = 71) plasma Aβ levels (cut-off: 761.45 pg/ml for Aβ40 and 10.74 pg/ml for Aβ42). Results: We observed significantly decreased FA and increased MD in the high Aβ40 group compared to the low Aβ40 group in various regions, including the body, the genu, and the splenium of the corpus callosum; the superior longitudinal fasciculus; the corona radiata; the thalamic radiation; the external and internal capsules; the inferior fronto-occipital fasciculus; and the sagittal stratum [p < 0.05, familywise error (FWE) corrected]. Average FA values were associated with poor performance on executive and memory assessments. No significant differences were found in either MD or FA between the low and high Aβ42 groups. Conclusion: Our results suggest that a correlation exists between WM integrity and plasma Aβ40 levels in individuals with SCD.
| S-EPMC7835390 | biostudies-literature