Strength together: examining risk and protective factors associated with dementia and cognitive impairment in Aboriginal and Torres Strait Islander peoples through harmonisation of landmark studies.

BACKGROUND: Rates of dementia for Aboriginal and Torres Strait Islander peoples are three to five times greater compared to non-Indigenous Australians, with earlier age of onset. However, the risk and protective factors that drive these higher rates vary across existing cohort studies, with minimal findings on the role of vascular risk factors beyond stroke. Harmonisation of data across studies may offer greater insights through enhanced diversity and strengthened statistical capabilities. This study aims to combine three landmark cohort studies of Aboriginal and Torres Strait Islander participants to better understand the determinants of cognitive health and dementia. METHODS/DESIGN: Three cohort studies - the Kimberley Healthy Adults Project (KHAP, N = 363), Koori Growing Old Well Study (KGOWS, N = 336) and Torres Strait Dementia Prevalence Study (TSDPS, N = 274) - share a similar research methodology with demographic, medical history, psychosocial factors, cognitive tests and consensus clinical diagnoses of cognitive impairment and dementia. Associations between risk and protective factors of interest and the presence of dementia and/or cognitive impairment diagnoses will be evaluated by univariable and multivariable logistic regression in a harmonised cross-sectional cohort of 898 participants. Factors associated with incident dementia and/or cognitive impairment will be assessed in a subset of KHAP (n = 189) and KGOWS participants (n = 165) who were available in longitudinal follow-up, after exclusion of those with baseline dementia or cognitive impairment. Analyses in relation to outcome measure of death or dementia will be conducted to account for the competing risk of death. Logistic regression will be used to evaluate the association between the individual components of the 16-component Kimberley Indigenous Cognitive Assessment (KICA) tool and the presence of dementia and cognitive impairment determined by independent consensus diagnoses. Multivariable binary logistic regression will be used to adjust for the effect of confounding variables. Results will be reported as odds ratios (OR) with 95% confidence intervals (95% CI). DISCUSSION: Greater understanding of risk and protective factors of dementia and cognitive impairment relevant to Aboriginal and Torres Strait Islander peoples may improve approaches across the life course to delay cognitive decline and reduce dementia risk.

Telephone cognitive screening with older Aboriginal Australians: A preliminary study.

OBJECTIVES: Cognitive screening via telehealth is increasingly employed, particularly during the COVID-19 pandemic. Telephone adaptations of existing cognitive screening tests must be validated across diverse populations. The present study sought to evaluate an existing 26-point telephone adaptation of the Mini-Mental State Examination (tMMSE) in a sample of older Aboriginal Australians. Additionally, we aimed to evaluate a telephone adaptation of the urban version of the Kimberley Indigenous Cognitive Assessment short-form (tKICA screen). METHODS: A sub-sample (n = 20) of participants (aged 55-69 years; 11 women) who had completed an in-person cognitive assessment (MMSE and KICA screen) within the past 6 months as part of the Koori Growing Old Well Study completed telephone-based cognitive testing without an assistant. RESULTS: There was moderate correlation and reasonable agreement between MMSE versions (rs  = 0.33; p = 0.2), although the limits of agreement were unacceptably wide (-4.1 and 4.8 points difference). Poorer performance was seen on the tMMSE for Season (p = 0.02) and Phrase (p = 0.02) items, and better performance for three-word Recall (p = 0.03). KICA-screen versions were poorly correlated (rs  = 0.20; p = 0.4) with telephone scoring a mean of 2.17 points below the face-to-face score, greater bias observed at the lower end of the performance and worse scores for Season (p = 0.02) and Recall (p = 0.001) items. Age and education were not associated with telephone screening performance. Hearing impairment was associated with poorer performance on the tKICA screen (p = 0.04) but not the tMMSE (p = 0.6). CONCLUSIONS: Results indicate that telephone administration of the MMSE and/or KICA screen is not equivalent to in-person testing for older Aboriginal people, and further revision and evaluation are required.

Dementia Incidence, APOE Genotype, and Risk Factors for Cognitive Decline in Aboriginal Australians: A Longitudinal Cohort Study.

BACKGROUND AND OBJECTIVES: Aboriginal Australians are disproportionately affected by dementia, with incidence in remote populations approximately double that of non-Indigenous populations. This study aimed to identify dementia incidence and risk factors in Aboriginal Australians residing in urban areas, which are currently unknown. METHODS: A population-based cohort of Aboriginal Australians ≥60 years of age was assessed at baseline and 6-year follow-up. Life-course risk factors (baseline) were examined for incident dementia or mild cognitive impairment (MCI) through logistic regression analyses; adjustments were made for age. APOE genotyping was available for 86 people. RESULTS: Data were included from 155 participants 60 to 86 years of age (mean 65.70 years, SD 5.65 years; 59 male). There were 16 incident dementia cases (age-standardized rate 35.97/1,000 person-years, 95% confidence interval [CI] 18.34-53.60) and 36 combined incident MCI and dementia cases. Older age (odds ratio [OR] 2.29, 95% CI 1.42-3.70), male sex (OR 4.14, 95% CI 1.60-10.77), unskilled work history (OR 5.09, 95% CI 1.95-13.26), polypharmacy (OR 3.11, 95% CI 1.17-8.28), and past smoking (OR 0.24, 95% CI 0.08-0.75) were associated with incident MCI/dementia in the final model. APOE ε4 allele frequency was 24%; heterozygous or homozygous ε4 was associated with incident MCI/dementia (bivariate OR 3.96, 95% CI 1.25-12.50). DISCUSSION: These findings provide evidence for higher dementia incidence in Aboriginal Australians from urban areas, where the majority of Aboriginal people reside. This study also sheds light on sociodemographic, health, and genetic factors associated with incident MCI/dementia at older ages in this population, which is critical for targeted prevention strategies.

Ngarraanga Giinganay ('thinking peacefully'): Co-design and pilot study of a culturally-grounded mindfulness-based stress reduction program with older First Nations Australians.

First Nations 'survivors' are ageing in increasing numbers. Life-course stress and depression are of concern for older First Nations Australians, yet there are limited psychosocial interventions. This study aimed to co-design a culturally-grounded mindfulness-based program ('Ngarraanga Giinganay') and evaluate acceptability/feasibility with an Aboriginal community on Gumbaynggirr Country. An expert Working Group guided program development, with Aboriginal and non-Aboriginal clinicians/consultants. A workshop, collaborative yarning group with older Aboriginal people (n = 9), and further consultation contributed to the design/refinement of the 8-session group-based program, ensuring content aligned with therapeutic principles of mindfulness and cultural understandings of the Gumbaynggirr community. A single-group pilot study was conducted (n = 7, 62-81 years), co-facilitated by an Aboriginal clinician and Elder. Outcomes were qualitative (understandings of mindfulness, program acceptability, benefits to health/wellbeing). Pilot results demonstrated feasibility, acceptability and preliminary effectiveness. The program enhanced understandings of mindfulness and participants highlighted benefits such as helping anxiety, relaxation, focusing on the moment and connection to Country/land. Trends were seen for reducing depression, anxiety and stress symptoms, and blood pressure. This study provides insight into partnering with underrepresented populations through ageing research, highlighting the effectiveness of this co-design approach. Ngarraanga Giinganay has considerable potential for supporting health and wellbeing of First Nations peoples.

Systematic review of coexistent epileptic seizures and Alzheimer's disease: Incidence and prevalence.

BACKGROUND/OBJECTIVES: Coexistent seizures add complexity to the burden of Alzheimer's disease (AD). We aim to estimate the incidence and prevalence of coexistent seizures and AD and summarize characteristics. DESIGN: A systematic review and meta-analysis (PROSPERO protocol registration CRD42020150479). SETTING: Population-, community-, hospital-, or nursing home-based. PARTICIPANTS AND MEASUREMENTS: Thirty-nine studies reporting on seizure incidence and prevalence in 21,198 and 380,777 participants with AD, respectively, and AD prevalence in 727,446 participants with seizures. When statistical heterogeneity and inconsistency (assessed by Q statistic and I2 ) were not shown, rates were synthesized using random effect. RESULTS: Studies were conducted in Australia, Brazil, Finland, France, Ireland, Italy, Japan, Netherlands, Portugal, Sweden, Taiwan, United Kingdom, and United States. The incidence of seizures among people with clinically diagnosed AD ranged from 4.2 to 31.5 per 1000 person-years. Prevalence of seizures among people with clinically diagnosed AD ranged from 1.5% to 12.7% generally, but it rose to the highest (49.5% of those with early-onset AD) in one study. Meta-analysis reported a combined seizure prevalence rate among people with pathologically verified AD at 16% (95% confidence interval [CI] 14-19). Prevalence of seizure in autosomal dominant AD (ADAD) ranged from 2.8% to 41.7%. Being younger was associated with higher risk of seizure occurrence. Eleven percent of people with adult-onset seizures had AD (95%CI, 7-14). CONCLUSION: Seizures are common in those with AD, and seizure monitoring may be particularly important for younger adults and those with ADAD.

Mild cognitive impairment in Aboriginal Australians.

INTRODUCTION: Aboriginal Australians have among the highest rates of dementia worldwide, yet no study has investigated the subtypes, risk factors, or longer term outcomes of mild cognitive impairment (MCI) in this population. METHODS: A total of 336 community-dwelling Aboriginal Australians aged ≥60 years participated in a longitudinal study, completing a structured interview at baseline. MCI (amnestic subtype, aMCI; non-amnestic subtype, naMCI) and dementia were diagnosed via cognitive screening, medical assessment, and clinical consensus. Associations between life-course factors and baseline MCI subtypes were examined using logistic regression. Conversion to dementia was assessed at 6-year follow-up. RESULTS: Prevalent aMCI (n = 24) was associated with older age (odds ratio [OR] = 1.68, 95% confidence interval [CI]: 1.12 to 2.53), head injury (OR = 3.19, 95% CI: 1.35 to 7.56), symptoms of depression (OR = 1.52, 95% CI: 1.04 to 2.24), and lower blood pressure (OR = 0.53, 95% CI: 0.33 to 0.86). Prevalent naMCI (n = 29) was associated with low education (OR = 4.46, 95% CI: 1.53 to 13.05), unskilled work history (OR = 5.62, 95% CI: 2.07 to 13.90), higher body mass index (OR = 1.99, 95% CI: 1.30 to 3.04), and moderate to severe hearing loss (OR = 2.82, 95% CI: 1.06 to 7.55). A small proportion of MCI cases reverted to intact at follow-up (15%), but most remained stable (44%), developed dementia and/or died (41%). DISCUSSION: Sociodemographic and clinical factors both contributed to baseline MCI and were distinct for MCI subtypes, with similar patterns of conversion to dementia for amnestic and non-amnestic MCI.

Staying in touch with the community: understanding self-reported health and research priorities in older Aboriginal Australians.

OBJECTIVES: Aboriginal Australians experience higher rates of non-communicable chronic disease, injury, dementia, and mortality than non-Aboriginal Australians. Self-reported health is a holistic measure and may fit well with Aboriginal views of health and well-being. This study aimed to identify predictors of self-reported health in older Aboriginal Australians and determine acceptable research methodologies for future aging research. DESIGN: Longitudinal, population-based study. SETTING: Five communities across New South Wales, Australia (two urban and three regional sites). PARTICIPANTS: Aboriginal and Torres Strait Islander people (n = 227; 60-88 years, M = 66.06, SD = 5.85; 145 female). MEASUREMENTS: Participants completed baseline (demographic, medical, cognitive, mental health, and social factors) and follow-up assessments (self-reported health quantified with 5-point scale; sharing thoughts on areas important for future research). Predictors of self-reported health were examined using logistic regression analyses. RESULTS: Self-reported health was associated with sex, activities of daily living, social activity participation, resilience, alcohol use, kidney problems, arthritis, falls, and recent hospitalization. Arthritis, kidney problems, and resilience remained significant in multiple logistic regression models. CONCLUSIONS: Perceived resilience and the absence of certain chronic age-related conditions predict older Aboriginal peoples' self-reported health. Understanding these factors could inform interventions to improve well-being. Findings on acceptable research methodologies suggest that many older Aboriginal people would embrace a range of methodologies within long-standing research partnerships, which is an important consideration for Indigenous population research internationally.

Characterization of Young and Old Adult Brains: An EEG Functional Connectivity Analysis.

Brain connectivity studies have reported that functional networks change with older age. We aim to (1) investigate whether electroencephalography (EEG) data can be used to distinguish between individual functional networks of young and old adults; and (2) identify the functional connections that contribute to this classification. Two eyes-open resting-state EEG recording sessions with 64 electrodes for each of 22 younger adults (19-37 years) and 22 older adults (63-85 years) were conducted. For each session, imaginary coherence matrices in delta, theta, alpha, beta and gamma bands were computed. A range of machine learning classification methods were utilized to distinguish younger and older adult brains. A support vector machine (SVM) classifier was 93% accurate in classifying the brains by age group. We report decreased functional connectivity with older age in delta, theta, alpha and gamma bands, and increased connectivity with older age in beta band. Most connections involving frontal, temporal, and parietal electrodes, and more than half of connections involving occipital electrodes, showed decreased connectivity with older age. Slightly less than half of the connections involving central electrodes showed increased connectivity with older age. Functional connections showing decreased strength with older age were not significantly different in electrode-to-electrode distance than those that increased with older age. Most of the connections used by the classifier to distinguish participants by age group belonged to the alpha band. Findings suggest a decrease in connectivity in key networks and frequency bands associated with attention and awareness, and an increase in connectivity of the sensorimotor functional networks with aging during a resting state.

Factors Associated with the High Prevalence of Dementia in Older Aboriginal Australians.

Dementia prevalence in Aboriginal and Torres Strait Islander Australians is three to five times higher than the general Australian population. A better understanding of the underlying biomedical and social risk factors is needed to guide dementia prevention in Aboriginal Australians. The current study is the first to examine potential risk factors for dementia in the majority urban and regional population, with a representative sample of 336 Aboriginal Australians aged 60 years and older. Participants included 45 people with a dementia diagnosis (n = 27 probable/possible Alzheimer's disease); and 286 people without dementia. Univariate logistic regression analyses (controlling for age) identified childhood trauma, mid-life factors (history of unskilled work, past high-risk alcohol use), and medical factors (history of stroke, head injury with loss of consciousness, epilepsy) as risk factors for dementia. Multivariable analysis revealed age, childhood trauma, unskilled work, stroke, and head injury as independent predictors of all-cause dementia. A range of comorbid factors related to dementia was also identified (i.e., functional impairment, incontinence, recent hospital admission, low body mass index, living in residential care, depression, current high-risk alcohol use, social isolation, low physical activity levels). These findings extend previous outcomes in a remote Aboriginal population by highlighting that life-course social determinants of health, in addition to neurological disorders, likely play an important role in elevating dementia risk. Certain psychosocial and medical exposures are highly prevalent in Aboriginal Australians, similar to other indigenous populations, and should be considered when designing targeted and culturally appropriate prevention initiatives to reduce the burden of dementia.

What Box: A task for assessing language lateralization in young children.

The assessment of active language lateralization in infants and toddlers is challenging. It requires an imaging tool that is unintimidating, quick to setup, and robust to movement, in addition to an engaging and cognitively simple language processing task. Functional Transcranial Doppler Ultrasound (fTCD) offers a suitable technique and here we report on a suitable method to elicit active language production in young children. The 34-second "What Box" trial presents an animated face "searching" for an object. The face "finds" a box that opens to reveal a to-be-labelled object. In a sample of 95 children (1 to 5 years of age), 81% completed the task-32% with ≥10 trials. The task was validated (ρ = 0.4) against the gold standard Word Generation task in a group of older adults (n = 65, 60-85 years of age), though was less likely to categorize lateralization as left or right, indicative of greater measurement variability. Existing methods for active language production have been used with 2-year-old children while passive listening has been conducted with sleeping 6-month-olds. This is the first active method to be successfully employed with infants through to pre-schoolers, forming a useful tool for populations in which complex instructions are problematic.

Is There a Link Between Cognitive Reserve and Cognitive Function in the Oldest-Old?

Background: The oldest-old (aged ≥85 years) are the fastest growing age group, with the highest risk of cognitive impairment and dementia. This study investigated whether cognitive reserve applies to the oldest-old. This has implications for cognitive interventions in this age group. Methods: Baseline and 5-year follow-up data from the Newcastle 85+ Study were used (N = 845, mean age = 85.5, 38% male). A Cognitive Reserve Index (CRI) was created, including: education, social class, marital status, engagement in mental activities, social participation, and physical activity. Global (Mini-Mental State Examination) and domain specific (Cognitive Drug Research Battery subtests assessing memory, attention, and speed) cognitive functions were assessed. Dementia diagnosis was determined by health records. Logistic regression analysis examined the association between CRI scores and incident dementia. Mixed effects models investigated baseline and longitudinal associations between the CRI scores and cognitive function. Analyses controlled for sex, age, depression, and cardiovascular disease history. Results: Higher reserve associated with better cognitive performance on all baseline measures, but not 5-year rate of change. The CRI associated with prevalent, but not incident dementia. Conclusions: In the oldest-old, higher reserve associated with better baseline global and domain-specific cognitive function and reduced risk of prevalent dementia; but not cognitive decline or incident dementia. Increasing reserve could promote cognitive function in the oldest-old. The results suggest there would be little impact on trajectories, but replication is needed. Development of preventative strategies would benefit from identifying the role of each factor in building reserve and why rate of change is not affected.

Cognitive reserve is not associated with improved performance in all cognitive domains.

Cognitive reserve beneficially affects cognitive performance, even into advanced age. However, the benefits afforded by high cognitive reserve may not extend to all cognitive domains. This study investigated whether cognitive reserve differentially affects performance on cognitive tasks, in 521 cognitively healthy individuals aged 60 to 98 years (Mage = 68, SD = 6.22, 287 female); years of education was used to index cognitive reserve. Cognitive performance variables assessed attention, executive functions, verbal memory, motor performance, orientation, perception of emotion, processing speed, and working memory. Bootstrapped regression analyses revealed that cognitive reserve was associated with attention, executive functions, verbal and working memory, and orientation; and not significantly related to emotion perception, processing speed, or motor performance. Cognitive reserve appears to differentially affect individual cognitive domains, which extends current theory that purports benefits for all domains. This finding highlights the possibility of using tests not (or minimally) associated with cognitive reserve, to screen for cognitive impairment and dementia in late life; these tests will likely best track brain health, free of compensatory neural mechanisms.

Social cognition is not associated with cognitive reserve in older adults.

Social and general cognitive abilities decline in late life. Those with high cognitive reserve display better general cognitive performance in old age; however, it is unknown whether this is also the case for social cognition. A total of 115 healthy older adults, aged 60-85 years (m = 44, f = 71) were assessed using The Awareness of Social Inference Test (TASIT-R; social cognition), the Lifetime of Experiences Questionnaire (LEQ; cognitive reserve), and the Wechsler Abbreviated Scale of Intelligence (WASI-II; general cognitive ability). The LEQ did not predict performance on any TASIT-R subtest: Emotion Evaluation Test (ß = -.097, p = .325), Social Inference - Minimal (ß = -.004, p = .972), or Social Inference - Enriched (ß = -.016, p = .878). Sensitivity analyses using two alternative cognitive reserve measures, years of education and the National Adult Reading Test, supported these effects. Cognitive reserve was strongly related to WASI-II performance. Unlike general cognitive ability, social cognition appears unaffected by cognitive reserve. Findings contribute to the emerging understanding that cognitive reserve differentially affects individual cognitive domains, which has implications for the theoretical understanding of cognitive reserve and its brain correlates. Cognitive measures unbiased by cognitive reserve may serve as best indicators of brain health, free of compensatory mechanisms.

Cerebrovascular function associated with fluid, not crystallized, abilities in older adults: A transcranial Doppler study.

The brain is dependent on the cerebrovascular system, particularly microvasculature, for a consistent blood supply; however, age-related changes in this system affect neuronal and therefore cognitive function. Structural vascular markers and vascular disease appear to preferentially affect fluid cognitive abilities, sparing crystallized abilities. We sought to investigate the relationships between cerebrovascular function and cognitive domains. Fifty individuals between 60 and 75 years of age (31 women, 19 men) underwent cognitive testing: Wechsler Vocabulary and Matrix Reasoning subtests (crystallized and fluid ability measures, respectively Wechsler, 2011), and the Addenbrooke's Cognitive Examination-Revised (ACE-R; general cognitive ability; Mioshi, Dawson, Mitchell, Arnold, & Hodges, 2006). Transcranial Doppler (TCD) measures were also collected at rest and during a cognitive word-generation task, from which a lateralization index was calculated. Lower pulsatility index at rest, and greater left lateralization during the TCD cognitive task were associated with better performance on the Matrix Reasoning but not the Vocabulary test; these effects were independent from each other and from any vascular comorbidity burden. These functional findings confirm previous structural studies, which revealed that fluid abilities are more vulnerable to cerebrovascular dysfunction than crystallized abilities, and identify two (likely related) mechanisms: degraded cerebrovascular integrity (indexed by pulsatility index) and a delateralization of function. Cerebrovascular dysfunction is a key contributor to cognitive aging that deserves further attention, particularly in relation to early diagnostic markers of impairment and monitoring of vascular (e.g., physical activity) interventions.