Patterns of change in subjective cognitive complaints are associated with cognitive decline and dementia risk: Findings from the Sydney Memory and Ageing Study

Background Subjective cognitive complaints (SCCs) are now an established risk factor for dementia, however, little is known about whether changing patterns in SCCs over time are associated with cognitive decline and dementia risk. We examine the trajectory of SCCs over a 6‐year period to determine whether intraindividual patterns of reporting SCCs over time is related to cognitive decline and incident dementia. Method Participants were 1037 older adults without dementia (M age = 78.65 years; 55% females) from the Sydney Memory and Ageing Study who were followed‐up biennially. Global cognition was measured using a comprehensive neuropsychological battery, and clinical diagnoses were made by an expert consensus panel. SCCs were obtained as participants’ response to a single question concerning their subjective report of memory decline. Patterns of SCCs over time were modelled by conducting categorical latent growth curve analysis using the logit transformation (Figure 1). We examined the associations between average level of SCC likelihood and change in SCC likelihood, with global cognition over six years using latent growth curve analysis, and with risk of incident dementia over 10 years using Cox regression. Result In this community‐dwelling older adult sample, there was an annual 10% increase in the odds of reporting SCCs (Figure 2). After controlling for demographics, depression, and personality, results revealed a negative longitudinal association between the slope of SCCs and the slope of global cognition scores, such that participants with an increasing propensity of reporting SCCs over time also showed a steeper rate of decline in global cognition (Figure 4). Cox regression revealed an association between increased SCCs and incident dementia risk (Table 1). That is, participants with an increasing propensity of reporting SCCs over time are also at greater risk for developing dementia (Figure 5). Conclusion This is the first study to use latent growth curve analysis to examine patterns of change in SCCs overtime. Traditionally, studies examining SCCs longitudinally categorise people as ‘stable’ versus ‘not stable’, however, important information may be lost this way. Understanding patterns of change in SCC reporting over time has significant potential to identify individuals at greater risk of cognitive decline and incident dementia

The heritability of subjective cognitive complaints in older Australian twins

Background Subjective cognitive complaints (SCCs) may be a precursor to mild cognitive impairment (MCI) and dementia. This study aimed to examine the heritability of SCCs, and the influence of personality and mood on the relationship between SCCs and memory performance. Method The heritability of SCCs were examined in 306 twin pairs using structural equation modelling. Genetic, environmental, and phenotypic correlations between SCCs and memory performance, personality, and mood scores were determined. Result SCCs were low to moderately heritable. Mood appeared to be related to SCCs by an environmental correlation, whereas memory performance was related to SCCs by a genetic correlation. SCCs had a significant amount of both genetic and environmental variances not explained by memory performance, personality, or mood. Conclusion Our results suggest that SCCs are influenced both by a person’s mood and their memory performance, and that these determinants are not mutually exclusive. Much of the genetic and environmental components to SCCs were specific to SCCs, with the specific factors yet to be determined

The latent construct of dementia phenotype: Validation and longitudinal examination in the Sydney Memory and Ageing Study

Background The latent continuous construct delta (δ) has been proposed as a novel approach to model dementia phenotype using structural equation modelling that reflects the “cognitive correlates of functional status” (Royall & Palmer, 2012. J Neuropsychiatry Clin Neurosci; Royall et al., 2012. J Alzheimers Dis). This δ factor has been demonstrated to be associated with clinically diagnosed dementia status and severity of dementia. However, thus far there are few studies validating the model longitudinally and these are in American samples. To establish the potential research and clinical utility of δ, the current research constructs and validates this latent dementia factor over a 6‐year period in a community sample of Australian older adults. Method A community‐dwelling sample of Australian older adults without dementia (at baseline) from the Sydney Memory and Ageing Study was used (n = 1037; M age = 78.65 years; 55% females). Biennially, participants completed a battery of neuropsychological tests measuring performance in four major cognitive domains, and informants rated their functional status on instrumental activities of daily living. Dementia status and severity were established through consensus diagnosis by an expert panel of clinicians and the Clinical Dementia Rating Scale Sum of Boxes (CDR‐SOB), respectively. Result A latent growth curve model of δ and Spearman’s general intelligence factor (g) built on four waves of cognitive and function data revealed good fit: CFI = 0.97, RMSEA = 0.04, SRMR = 0.06. A significant increase in δ over time was observed, and this latent change in δ (Δδ) was significantly associated with CDR‐SOB at wave 4 after controlling for demographics, APOE*4, and baseline CDR‐SOB. Cox regression revealed a significant association between Δδ and incident dementia. Further, Δδ accurately discriminated diagnosed dementia cases at wave 4 (ROC area under the curve = 0.91, 95% CI [0.88, 0.95]). Conclusion This study tests and validates the δ framework in Australian older adults by demonstrating that the change in δ over 6 years is associated with dementia risk and prospective severity of dementia. Future research should further test the model using longitudinal data from geographically and ethnoculturally diverse samples

Social cognitive abilities in older adults with mild cognitive impairment and dementia

Background Aging is associated with changes in general cognition and social cognition. Many studies have detailed these functions in isolation, comparing young and older adults. More information is needed on how social cognition, including theory of mind (ToM), affective empathy (AE), social perception (SP), and social behavior (SB), is affected at different cognitive stages in older adults. Method Cross‐sectional study of 305 older adults from the Sydney Memory and Ageing Study. Dementia was classified based on clinical consensus using DSM‐IV criteria, while mild cognitive impairment (MCI) was classified using the International Working Group criteria. Cognitively normal (CN), MCI, and dementia participants were compared on social cognitive domains including: ToM, via the Reading the Mind in the Eyes Test (RMET) and the Interpersonal Reactivity Index – Perspective Taking subscale (IRI‐PT); AE, via the IRI – Empathic Concern subscale (IRI‐EC); and SP, via the Emotion Recognition Task (ERT). Apathy, which is related to SB, was measured via the Apathy Evaluation Scale (AES). Result Mean age 87.00 ± 4.05 years, mean education 11.89 ± 3.36 years, 60.3% female. 141 were CN, 103 had MCI, and 61 had dementia. Across cognitive groups, significant differences were observed for the RMET, ERT (specifically for the recognition of anger, disgust, and happiness), AES, IRI‐PT, and IRI‐EC. In posthoc comparisons, RMET and ERT were significantly poorer in MCI and dementia compared to CN, but not between MCI and dementia. IRI ratings and AES were poorer for dementia compared to MCI and CN, but not between MCI and CN (Table 1). In multivariable logistic regression adjusting for significant risk factors for cognitive impairment, RMET and ERT disgust performance were associated with lower risk of MCI over CN. Only AES significantly differentiated dementia from MCI (Table 2). Conclusion Neurocognitive disorders are associated with social cognition changes. ToM and SP appear to be affected in MCI relative to CN. Apathy, known to be linked to SB, appears to be affected in dementia. MCI seems to be associated with impaired ability to recognize specific social cognitive cues, while dementia may be more associated with overall worse social cognitive functioning and observed behavioral changes

Polygenic resilience scores capture protective genetic effects for Alzheimer’s disease

Polygenic risk scores (PRSs) can boost risk prediction in late-onset Alzheimer’s disease (LOAD) beyond apolipoprotein E (APOE) but have not been leveraged to identify genetic resilience factors. Here, we sought to identify resilience-conferring common genetic variants in (1) unaffected individuals having high PRSs for LOAD, and (2) unaffected APOE-ε4 carriers also having high PRSs for LOAD. We used genome-wide association study (GWAS) to contrast “resilient” unaffected individuals at the highest genetic risk for LOAD with LOAD cases at comparable risk. From GWAS results, we constructed polygenic resilience scores to aggregate the addictive contributions of risk-orthogonal common variants that promote resilience to LOAD. Replication of resilience scores was undertaken in eight independent studies. We successfully replicated two polygenic resilience scores that reduce genetic risk penetrance for LOAD. We also showed that polygenic resilience scores positively correlate with polygenic risk scores in unaffected individuals, perhaps aiding in staving off disease. Our findings align with the hypothesis that a combination of risk-independent common variants mediates resilience to LOAD by moderating genetic disease risk

The Influences of partner accuracy and partner memory ability on social false memories

In this study, we examined whether increasing the proportion of false information suggested by a confederate would influence the magnitude of socially introduced false memories in the social contagion paradigm Roediger, Meade, & Bergman (Psychonomic Bulletin & Review 8:365–371, 2001). One participant and one confederate collaboratively recalled items from previously studied household scenes. During collaboration, the confederate interjected 0%, 33%, 66%, or 100% false items. On subsequent individual-recall tests across three experiments, participants were just as likely to incorporate misleading suggestions from a partner who was mostly accurate (33 % incorrect) as they were from a partner who was not at all accurate (100% incorrect). Even when participants witnessed firsthand that their partner had a very poor memory on a related memory task, they were still as likely to incorporate the confederate’s entirely misleading suggestions on subsequent recall and recognition tests (Exp. 2). Only when participants witnessed firsthand that their partner had a very poor memory on a practice test of the experimental task itself were they able to reduce false memory, and this reduction occurred selectively on a subsequent individual recognition test (Exp. 3). These data demonstrate that participants do not always consider their partners’ memory ability when working on collaborative memory tasks.14 page(s

Ageing stereotypes influence the transmission of false memories in the social contagion paradigm

These experiments are the first to investigate the impact of confederate accuracy, age, and age stereotypes in the social contagion of memory paradigm. Across two experiments, younger participants recalled household scenes with an actual (Experiment 1) or virtual (Experiment 2), older or younger confederate who suggested different proportions (0%, 33% or 100%) of false items during collaboration. In Experiment 2, positive and negative age stereotypes were primed by providing bogus background information about our older confederate before collaboration. Across both experiments, if confederates suggested false items participants readily incorporated these into their own memory reports. In Experiment 1, when no age stereotype was primed, participants adopted similar proportions of false items from younger and older confederates. Importantly, in Experiment 2, when our older confederate was presented in terms of negative ageing stereotypes, participants reported less false items and were better able to correctly identify the source of those false items

Polygenic resilience scores capture protective genetic effects for Alzheimer's disease.

Polygenic risk scores (PRSs) can boost risk prediction in late-onset Alzheimer's disease (LOAD) beyond apolipoprotein E (APOE) but have not been leveraged to identify genetic resilience factors. Here, we sought to identify resilience-conferring common genetic variants in (1) unaffected individuals having high PRSs for LOAD, and (2) unaffected APOE-ε4 carriers also having high PRSs for LOAD. We used genome-wide association study (GWAS) to contrast "resilient" unaffected individuals at the highest genetic risk for LOAD with LOAD cases at comparable risk. From GWAS results, we constructed polygenic resilience scores to aggregate the addictive contributions of risk-orthogonal common variants that promote resilience to LOAD. Replication of resilience scores was undertaken in eight independent studies. We successfully replicated two polygenic resilience scores that reduce genetic risk penetrance for LOAD. We also showed that polygenic resilience scores positively correlate with polygenic risk scores in unaffected individuals, perhaps aiding in staving off disease. Our findings align with the hypothesis that a combination of risk-independent common variants mediates resilience to LOAD by moderating genetic disease risk

Polygenic resilience scores capture protective genetic effects for Alzheimer’s disease

Polygenic risk scores (PRSs) can boost risk prediction in late-onset Alzheimer’s disease (LOAD) beyond apolipoprotein E (APOE) but have not been leveraged to identify genetic resilience factors. Here, we sought to identify resilience-conferring common genetic variants in (1) unaffected individuals having high PRSs for LOAD, and (2) unaffected APOE-ε4 carriers also having high PRSs for LOAD. We used genome-wide association study (GWAS) to contrast “resilient” unaffected individuals at the highest genetic risk for LOAD with LOAD cases at comparable risk. From GWAS results, we constructed polygenic resilience scores to aggregate the addictive contributions of risk-orthogonal common variants that promote resilience to LOAD. Replication of resilience scores was undertaken in eight independent studies. We successfully replicated two polygenic resilience scores that reduce genetic risk penetrance for LOAD. We also showed that polygenic resilience scores positively correlate with polygenic risk scores in unaffected individuals, perhaps aiding in staving off disease. Our findings align with the hypothesis that a combination of risk-independent common variants mediates resilience to LOAD by moderating genetic disease risk