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Background: The SKT is a short cognitive performance test designed to assess impairments in memory and cognitive abilities such as attention and speed of information processing. In 2019, new regression-based norms for the English version of the SKT were calculated. This study has two aims: to establish valid cut-offs for distinguishing between no cognitive impairment, mild cognitive impairment (MCI), and dementia (1) and to cross-validate the new norms for detecting MCI and dementia in a community sample of older adults with clinical diagnoses (2). Methods: The validation sample included 143 older adults (mean age = 87.7, SD = 3.55) from the Sydney Memory and Aging Study (MAS Study). Participants were classified as having normal cognition, MCI, or dementia solely based on a consensus diagnosis; in addition, three tests (SKT, Mini-Mental State Examination (MMSE), and Addenbrooke’s Cognitive Examination III (ACE-III)) to measure cognitive impairment were applied. Sensitivity and specificity for all three tests, as well as bivariate correlations, were calculated. Results: The sensitivity of the SKT for the differentiation of cognitive impairment (MCI or dementia) from normal cognition was 80.6%. The convergence between the SKT and the consensus diagnoses was 70.3% for all three diagnostic groups. All correlations between the three tests and the consensus diagnosis were significant (p < 0.01). Conclusions: In sum, it can be stated that the SKT is a valid tool for detecting early stages of cognitive impairment, performing very well in discriminating between no cognitive impairment and cognitive impairment (MCI or dementia).

Objectives: Nowadays, the number of older people is increasing rapidly, both in absolute figures and as a proportion of the population, which makes the maintenance of psychological well-being among aging population imperative. Neuropsychological distress may promote cognitive impairment and impact on the health of older people, which makes accurate assessment of distress an important clinical and research issue. The Kessler Psychological Distress Scale (K-10) is a widely used instrument used to measure individual distress. However, the ability of K-10 to distinguish between enduring and dynamic distress symptoms, and the generalizability of its scores, have not been investigated in older populations using appropriate methodology. Method: Generalizability theory (G-theory) was applied to differentiate enduring and dynamic distress and examine the reliability of K-10 in a sample of 201 adults (43% males) aged 70 to 90 years old who participated in Sydney Memory and Ageing Study. The data were collected biennially over ten years. Results: The K-10 scale showed strong reliability (Ga=0.81, Gr=0.89) in assessing enduring distress and its assessment scores were generalizable across occasions and older adults. Most of distress symptoms represented by K-10 items were enduring. Limitations: Generalizability of these findings may be limited to older adults. Conclusions: The K-10 appears more suitable to evaluate enduring distress in aging populations over time, which is important for interventions targeting older adults’ mental health given its scores will likely capture enduring changes in neuropsychological health before and after interventions.

Abstract 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.

BackgroundIndividuals with subjective cognitive complaints (SCCs) are at an increased risk of dementia. Questions remain about participant-reported versus informant-reported SCCs as indicators of future dementia and about longitudinal changes in participant-and informant-reported SCCs and risk of incident dementia.MethodParticipants were 873 older adults (M = 78.65-years; 55% female) and 849 informants from the Sydney Memory and Ageing Study. Comprehensive assessments occurred biennially, and clinical diagnoses were made by expert consensus for 10-years. SCCs were participants’ and informants’ responses to a single binary question concerning their/the participant’s memory decline (Yes/No) over the first 6-years. Categorical latent growth curve analyses, using the logit transformation, were used to model SCC change over time. Associations of initial propensity to report SCCs at baseline, and change in propensity to report SCCs over time, with dementia risk were examined using Cox regression.Results70% of participants reported SCCs at baseline, with a proportional increase in the odds of reporting by 11% for each additional year in the study. In contrast, 22% of informants reported SCCs at baseline, with a proportional increase by 30% in the odds of reporting per year. Participants’ initial level of (p = 0.007), but not change in SCC reporting (p = 0.179), was associated with risk of dementia controlling for all covariates. Both informants’ initial level of (p

ObjectivePrevious research shows that depression and personality are independently associated with self- and informant-reports of the ability to perform instrumental activities of daily living (IADLs). However, less is known about the association between depression and personality and performance-based measures of IADLs. We aimed to determine how depression and personality predict self-and informant-reports of IADL compared to performance-based measures of IADLs in a sample of older adults with normal cognition (NC) and Mild Cognitive Impairment (MCI).MethodsParticipants consisted of 385 older adults with NC (n = 235), or a diagnosis of MCI (n = 150), aged between 76 and 99-years from the Sydney Memory and Ageing Study. Participants underwent comprehensive neuropsychological and clinical assessments to determine global cognition and clinical diagnoses. Personality traits were measured by the NEO Five-Factor Inventory (NEO-FFI) and depression by the Geriatric Depression Scale (GDS). Subjective IADLs were self- and informant-reported Bayer Activities of Daily Living (B-ADL) scales and objective IADL was the Sydney Test of Activities of Daily Living in Memory Disorders (STAM). Linear regressions examined the relationship between depression and personality and the three types of IADL measures, controlling for all covariates and global cognition.ResultsParticipant-reported IADL, although associated with global cognition, was more strongly associated with GDS and NEO-FFI scores (conscientiousness and neuroticism). Informant-reported IADL was strongly associated with both global cognition and participants’ GDS scores. STAM scores were not associated with participants’ GDS or NEO-FFI scores; instead, they were predicted by demographics and global cognition.ConclusionThese results suggest that performance-based measures of IADL may provide more objective and reliable insight into an individual’s underlying functional ability and are less impacted by the participants’ mood and personality compared to subjectively reported IADL. We argue that performance-based IADL measures are preferable when trying to accurately assess everyday functional ability and its relationship to cognitive status. Where performance-based measures are not available (e.g., in some clinical settings), informant ratings should be sought as they are less influenced by the participant’s personality and mood compared to self-reports.

Abstract Efficient identification of cognitive decline and Alzheimer's disease (AD) risk in early stages of the AD disease continuum is a critical unmet need. Subjective cognitive decline is increasingly recognized as an early symptomatic stage of AD. Dyadic cognitive report, including subjective cognitive complaints (SCC) from a participant and an informant/study partner who knows the participant well, represents an accurate, reliable, and efficient source of data for assessing risk. However, the separate and combined contributions of self‐ and study partner report, and the dynamic relationship between the two, remains unclear. The Subjective Cognitive Decline Professional Interest Area within the Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment convened a working group focused on dyadic patterns of subjective report. Group members identified aspects of dyadic‐report information important to the AD research field, gaps in knowledge, and recommendations. By reviewing existing data on this topic, we found evidence that dyadic measures are associated with objective measures of cognition and provide unique information in preclinical and prodromal AD about disease stage and progression and AD biomarker status. External factors including dyad (participant–study partner pair) relationship and sociocultural factors contribute to these associations. We recommend greater dyad report use in research settings to identify AD risk. Priority areas for future research include (1) elucidation of the contributions of demographic and sociocultural factors, dyad type, and dyad relationship to dyad report; (2) exploration of agreement and discordance between self‐ and study partner report across the AD syndromic and disease continuum; (3) identification of domains (e.g., memory, executive function, neuropsychiatric) that predict AD risk outcomes and differentiate cognitive impairment due to AD from other impairment; (4) development of best practices for study partner engagement; (5) exploration of study partner report as AD clinical trial endpoints; (6) continued development, validation, and optimization, of study partner report instruments tailored to the goals of the research and population.

Subjective Cognitive Complaints (SCCs) may represent one of the earliest stages of preclinical dementia. The objective of the present study was to extend previous work by our group to examine the relationship between participant-reported and informant-reported memory and non-memory SCCs, cognitive decline and incident dementia, over a six-year period. Participants were 873 community dwelling older adults (Mage = 78.65, SD = 4.79) without dementia and 843 informants (close friends or family) from the Sydney Memory and Ageing Study. Comprehensive neuropsychological testing and diagnostic assessments were carried out at baseline and biennially for six years. Linear mixed models and Cox proportional hazard models were performed to determine the association of SCCs, rate of cognitive decline and risk of incident dementia, controlling demographics and covariates of mood and personality. Participant and informant memory-specific SCCs were associated with rate of global cognitive decline; for individual cognitive domains, participant memory SCCs predicted decline for language, while informant memory SCCs predicted decline for executive function and memory. Odds of incident dementia were associated with baseline participant memory SCCs and informant memory and non-memory SCCs in partially adjusted models. In fully adjusted models, only informant SCCs were associated with increased risk of incident dementia. Self-reported memory-specific cognitive complaints are associated with decline in global cognition over 6-years and may be predictive of incident dementia, particularly if the individual is depressed or anxious and has increased neuroticism or decreased openness. Further, if and where possible, informants should be sought and asked to report on their perceptions of the individual's memory ability and any memory-specific changes that they have noticed as these increase the index of diagnostic suspicion.

BackgroundWith no effective treatments for cognitive decline or dementia, improving the evidence base for modifiable risk factors is a research priority. This study investigated associations between risk factors and late-life cognitive decline on a global scale, including comparisons between ethno-regional groups.Methods and findingsWe harmonized longitudinal data from 20 population-based cohorts from 15 countries over 5 continents, including 48,522 individuals (58.4% women) aged 54-105 (mean = 72.7) years and without dementia at baseline. Studies had 2-15 years of follow-up. The risk factors investigated were age, sex, education, alcohol consumption, anxiety, apolipoprotein E ε4 allele (APOE*4) status, atrial fibrillation, blood pressure and pulse pressure, body mass index, cardiovascular disease, depression, diabetes, self-rated health, high cholesterol, hypertension, peripheral vascular disease, physical activity, smoking, and history of stroke. Associations with risk factors were determined for a global cognitive composite outcome (memory, language, processing speed, and executive functioning tests) and Mini-Mental State Examination score. Individual participant data meta-analyses of multivariable linear mixed model results pooled across cohorts revealed that for at least 1 cognitive outcome, age (B = -0.1, SE = 0.01), APOE*4 carriage (B = -0.31, SE = 0.11), depression (B = -0.11, SE = 0.06), diabetes (B = -0.23, SE = 0.10), current smoking (B = -0.20, SE = 0.08), and history of stroke (B = -0.22, SE = 0.09) were independently associated with poorer cognitive performance (p < 0.05 for all), and higher levels of education (B = 0.12, SE = 0.02) and vigorous physical activity (B = 0.17, SE = 0.06) were associated with better performance (p < 0.01 for both). Age (B = -0.07, SE = 0.01), APOE*4 carriage (B = -0.41, SE = 0.18), and diabetes (B = -0.18, SE = 0.10) were independently associated with faster cognitive decline (p < 0.05 for all). Different effects between Asian people and white people included stronger associations for Asian people between ever smoking and poorer cognition (group by risk factor interaction: B = -0.24, SE = 0.12), and between diabetes and cognitive decline (B = -0.66, SE = 0.27; p < 0.05 for both). Limitations of our study include a loss or distortion of risk factor data with harmonization, and not investigating factors at midlife.ConclusionsThese results suggest that education, smoking, physical activity, diabetes, and stroke are all modifiable factors associated with cognitive decline. If these factors are determined to be causal, controlling them could minimize worldwide levels of cognitive decline. However, any global prevention strategy may need to consider ethno-regional differences.