Lisa Bransby

Background: In Australia, access to Alzheimer's disease (AD) therapeutics requires apolipoprotein E ( APOE ) genotype testing and disclosure, yet the feasibility, acceptability and tolerability of APOE disclosure in an Australian context remains unknown. Objective: This pilot study evaluated a researcher-delivered, videoconferencing-based APOE disclosure protocol in cognitively unimpaired (CU) Australian adults with dementia family history. Methods: The DISCLOSE- APOE protocol, informed by prior expert approaches and Australian consumer preferences, was piloted in fifteen CU adults aged 40–70 (8 ε4 carriers, 7 non-carriers). The protocol comprised 7 online sessions, including mood/suicide risk assessment, education, and psychological readiness evaluation. APOE genotype was disclosed 1:1 via videoconferencing using a standardized interaction procedure. Existing data and online questionnaires assessed participant characteristics and outcomes pre- and post-disclosure. Paired-samples t-tests examined within-group mood changes, and independent-samples t-tests compared post-disclosure test-/event-related distress between carriers and non-carriers. Results: All participants (M age = 60.8 (±6.4), 60% female) completed the pilot, and no adverse events occurred. Baseline mood was equivalent across groups. Anxiety decreased post-disclosure in both ε4 carriers and non-carriers. Depressive symptoms increased slightly but not significantly in ε4 carriers and remained sub-threshold. Test-related distress was moderately higher in ε4 carriers post-disclosure. Conclusions: Researcher-delivered and remote APOE disclosure via videoconferencing resulted in no attrition nor clinically-significant short-term psychological distress, with pilot data providing preliminary evidence of feasibility, acceptability and tolerability in this cohort. Findings will inform the development and implementation of culturally-appropriate and scalable APOE disclosure protocols in research and clinical settings to facilitate delivery of anti-Aβ therapies in Australia.

Background: In people at risk of Alzheimer’s disease (AD), access to cognitive assessment can be increased through internet‐based registries, which can be linked to disease management clinics for comprehensive follow‐up. The Cogstate Brief Battery (CBB) has been optimized for unsupervised use in registries. This study aimed to determine relationships between performance on the unsupervised CBB, defined using conventional Cognigram and novel composite scores, and in‐clinic CSF AD biomarkers and cognition in middle‐aged adults at‐risk of AD.Method: Seventy‐six cognitively unimpaired (CU) adults (67% female; Mage (SD) 58.4(6.7)) enrolled in the Healthy Brain Project (healthybrainproject.org.au) completed unsupervised CBB assessments, and subsequent in‐clinic assessment of AD biomarkers and cognition. CBB tests included DET (psychomotor‐function), IDN (attention), OCL (learning) and OBK (working memory). The Cognigram Learning/Working Memory Composite, and the Cognigram Psychomotor/Attention composite were derived from these. Two novel composites were also computed: the OCL speed/accuracy composite, and OCL‐OBK speed/accuracy composite. In‐clinic assessments included the International Shopping List, Logical Memory, and Digit Symbol Substitution Tests, and Mini Mental Status Examination to provide a Preclinical Alzheimer’s Cognitive Composite (PACC) score. CSF Aβ42, total tau (t‐tau), and tau phosphorylated at threonine 181 (p‐tau181) were measured by immunoassay (Roche Elecsys®) and CSF neurofilament light (NfL) was measured using ELISA. Associations with CSF Aβ42, t‐tau, p‐tau181, NfL and PACC were determined for each CBB composite with age, sex, education, APOE4 and time difference between unsupervised and in‐clinic assessment controlled statistically.Result: The Cognigram Learning/Working memory composite, the OCL speed/accuracy composite, and the OCL‐OBK speed/accuracy composite were associated with PACC scores and with t‐tau, p‐tau181, and NfL levels. Magnitude of relationships were similar across composites (Table 1). No cognitive composite was associated with CSF Aβ42. Performance on the Cognigram Psychomotor/Attention composite was unrelated to AD biomarkers or PACC scores.Conclusion: In CU adults, unsupervised performance on CBB composites containing learning and working memory measures were associated strongly with in‐clinic neuropsychological outcomes and AD biomarkers. Remote measurement of cognition can validly assess aspects of learning and working memory disrupted by early AD processes such as increases in tau, and could be useful for identification of individuals with early disease.

Background: The International Shopping List test (ISLT) is a verbal word list learning test set within a realistic shopping list context, supporting ease of cultural adaptation, and addressing content validity and patient relevance. Improvements to and the wide adoption of natural language processing (NLP) software has enabled the possibility for self‐administered tests of verbal learning. Lila^TM a self‐administered, smartphone‐application (app) was developed, using the virtual assistant and NLP. We have previously reported acceptability and usability data from qualitative analysis of concept elicitation interviews. We now seek to provide preliminary validation data around its use.Method: A convenience sample of healthy young adults (n = 40), M(SD)age = 35 (16), were invited to install and complete one assessment of the Lila^TM app. A usability survey was also administered to explore participants’ experiences. The sample was predominantly female (70%) and of Asian ethnicity (62.5%). Data were collected in Australia, using an English word pool developed for the USA.Result: Acceptability was generally high with N = 38 completing immediate recall rounds and N = 32 completing the delayed recall round. Eight‐two percent found it extremely or somewhat easy to hear and understand what items were on the shopping list and 95% indicated that it was extremely or somewhat easy to understand what they had to do to complete the assessment. Scoring accuracy was 88% at the word item level, with reprocessing to address accent, context setting, and other NLP approaches to improve accuracy underway e.g., homophones biased to the grocery item.Conclusion: Whilst acceptability was high, the importance of localization of test stimuli was confirmed as well as the need for additional data processing options to account for accent. Continued optimization of data processing to score participant responses and word item pools to reduce ambiguity is expected to further improve accuracy e.g., accounting for regional accents and consideration of homophones and compound words. However, specific characteristics of speech including in those for whom English may be a second/foreign language will be an area of focus for future development.

Background: Self‐reported psychological stress is associated with an increased risk of cognitive decline and dementia. However, it remains unclear whether stress is related to key biomarkers of Alzheimer’s disease (AD). This cross‐sectional study examined the relationship of psychological stress with memory and cerebrospinal fluid (CSF) biomarkers of AD in middle‐aged adults without dementia.Method: The Healthy Brain Project (HBP) is a prospective web‐based study of adults aged between 40 and 70 years. A total of 2208 participants (76% female) completed the Depression, Anxiety, and Stress Scale (DASS) and Paired Associates Learning subtest of the CANTAB unsupervised on the HBP web platform. Additionally, a sub‐group of participants (n = 67; 41% APOE e4 carriers) attended an in‐person assessment where CSF samples were obtained to measure levels of amyloid‐beta (Aβ42), total tau (t‐tau), phosphorylated tau 181 (p‐tau), and neurofilament light chain (NFL). Separate linear regression analyses investigated associations of the DASS‐Stress score with memory performance and AD biomarkers. All analyses were adjusted for age, sex, education, and race.Result: In the web‐based cohort, higher levels of self‐reported psychological stress were significantly associated with poorer memory (unstandardised β = ‐0.014, standard error [SE] = 0.004, p <.001). However, there were no significant associations between psychological stress and CSF levels of Aβ42, t‐tau, p‐tau, and NFL (all p > .05), with small effect sizes (Cohen’s f² ≤ 0.05).Conclusion: Higher levels of self‐reported psychological stress were associated with poorer memory in a large middle‐aged cohort but were not associated with AD biomarkers in a subset of participants with available CSF. One potential explanation is that non‐AD pathologies may underlie the relationship between stress and poorer memory; for example, poor coping strategies (e.g., smoking, overeating, and physical activity) might increase the risk of vascular cognitive impairment. However, it is also likely that the small sample size of the in‐clinic cohort was insufficient to detect any subtle relationships between stress and AD pathologies. Further research is needed to determine the associations between stress and the development of the clinical and biological manifestations of AD.

Many risk factors for dementia, identified from observational studies, are potentially modifiable. This raises the possibility that targeting key modifiabl

Studies of modifiable dementia risk factors (MDRFs) generally consider MDRFs individually, despite strong evidence that they co-occur in adult populations. In a large sample of middle-aged adults, this study aimed to determine the frequency and co-occurrence of MDRFs, spanning five domains (mood symptomatology, risky lifestyle behaviors, cardiovascular conditions, cognitive/social engagement, sleep disorders/symptomatology). The relationship between number of domains in which MDRFs were reported with cognitive performance and subjective cognitive concerns was then determined. Middle-aged adults (n = 1,610) enrolled in the Healthy Brain Project and completed self-report surveys about their health and lifestyle. Participants also completed the Cogstate Brief Battery and the Cognitive Function Instrument, a measure of subjective ratings of cognition. Participants were classified according to number of domains (mood symptomatology, risky lifestyle behaviors, cardiovascular conditions, cognitive/social engagement, sleep disorders/symptomatology) in which they reported at least one MDRF (0-5). Age, sex, education, and ethnicity were adjusted for in analyses. Most individuals (66.5%) reported MDRFs in two or more domains. Compared with individuals displaying no MDRFs, individuals with MDRFs in 3-5 domains showed worse learning/working memory performance and greater subjective cognitive concerns, with the magnitude of these differences moderate-to-large (d = 0.30-0.93). Individuals displaying MDRFs in five domains also showed worse attention/psychomotor function (d = 0.58) compared to those displaying no MDRFs. These findings may suggest that multidomain MDRFs are highly frequent in middle-aged adults and are related to poorer cognition. This supports that modifiable dementia risk is multidimensional and raises the possibility that multidomain behavioral intervention trials in middle-aged adults may be useful to delay or prevent cognitive impairment or decline. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Background: A range of lifestyle factors in midlife can increase risk for developing dementia in late‐life.¹ However, it remains unclear whether the presence of such risk factors (RFs) is associated with individuals’ insight into their risk of developing dementia. In a group of middle‐aged adults with a family history of dementia enrolled in a lifestyle prevention trial, we measured associations between modifiable RF prevalence, subjective cognitive concerns, and perceived susceptibility to dementia.Method: Participants (n = 456) enrolled in BetterBrains (betterbrains.org.au)² completed a comprehensive self‐report RF assessment at baseline. Modifiable dementia risk was determined across four domains (vascular health, social/cognitive engagement, mood, sleep) and trial eligibility required risk in at least one domain. Participants were grouped according to the number of domains in which they reported high‐risk (ranging from 1‐4). Participants completed the Cognitive Function Instrument, and a brief questionnaire to assess perceived susceptibility to dementia (Motivation to Change Lifestyle/Health Behaviours for Dementia Risk Reduction scale). Linear regressions examined associations between modifiable RF prevalence, subjective cognition, and perceived susceptibility to dementia, adjusting for age, sex, education, negative beliefs about ageing, and beliefs about protective health behaviours on dementia risk.Result: Participants were mostly female (80%), with an average age of 59.4 years and 15.2 years of education. Of the sample, 29.6% reported risk in all domains (29.6%) and 16.9% in three domains. Risk in a higher number of RF domains was significantly associated with greater subjective cognitive concerns (β(SE) = 0.18(0.06), p = <.001), but not with greater perceived susceptibility to developing dementia (β(SE) = 0.62(0.35), p = .08). Increasingly negative beliefs about ageing and weaker beliefs in the protective effect of health behaviours were the only significant predictors of perceived susceptibility to dementia (both p’s <.05).Conclusion: In middle‐aged adults, dementia RFs are associated with greater subjective cognitive concerns, but not with an increased perception of susceptibility to dementia. Incongruence between participants’ self‐report of subjective cognitive concerns and susceptibility to dementia may be due in part to poor knowledge on modifiable dementia RFs.³ Perceptions of personal susceptibility to dementia may also be tied more closely to negative ageing stereotypes typically associated with older age and family history of disease.

Background and Objectives This prospective study sought to determine the association of modifiable/nonmodifiable components included in the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) risk score with hippocampal volume (HV) loss and episodic memory (EM) decline in cognitively normal (CN) older adults classified as brain β-amyloid (Aβ) negative (Aβ−) or positive (Aβ+). Methods Australian Imaging, Biomarkers and Lifestyle study participants (age 58–91 years) who completed ≥2 neuropsychological assessments and a brain Aβ PET scan (n = 592) were included in this study. We computed the CAIDE risk score (age, sex, APOE ε4 status, education, hypertension, body mass index [BMI], hypercholesterolemia, physical inactivity) and a modifiable CAIDE risk score (CAIDE-MR; education, hypertension, BMI, hypercholesterolemia, physical inactivity) for each participant. Aβ+ was classified using Centiloid >25. Linear mixed models assessed interactions between each CAIDE score, Aβ group, and time on HV loss and EM decline. Age, sex, and APOE ε4 were included as separate predictors in CAIDE-MR models to assess differential associations. Exploratory analyses examined relationships between individual modifiable risk factors and outcomes in Aβ− cognitively normal (CN) adults. Results We observed a significant Aβ group × CAIDE × time interaction on HV loss (β [SE] = –0.04 [0.01]; p < 0.000) but not EM decline (β [SE] = –2.33 [9.96]; p = 0.98). Decomposition revealed a significant CAIDE × time interaction in Aβ+ participants only. When modifiable/nonmodifiable CAIDE components were considered separately, we observed a significant Aβ group × CAIDE-MR × time interaction on EM decline only (β [SE] = 3.03 [1.18]; p = 0.01). A significant CAIDE-MR score × time interaction was observed in Aβ− participants only. Significant interactions between APOE ε4 and age × time on HV loss and EM decline were observed in both groups. Exploratory analyses in Aβ− CN participants revealed a significant interaction between BMI × time on EM decline (β [SE] = –3.30 [1.43]; p = 0.02). Discussion These results are consistent with studies showing that increasing age and APOE ε4 are associated with increased rates of HV loss and EM decline. In Aβ− CN adults, lower prevalence of modifiable cardiovascular risk factors was associated with less HV loss and EM decline over ∼10 years, suggesting interventions to reduce modifiable cardiovascular risk factors could be beneficial in this group.