Psychiatry - Research Publications

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The effect of sad mood on subjective appraisal of memory performance in older people with and without subjective memory complaints: An experimental study

Farmer, HF ; Bahar‐Fuchs, A ; Bryant, C (Wiley, 2021-12)

Background Subjective memory complaints (SMC) have been identified as a possible precursor to cognitive decline and may indicate a need for an early intervention for at‐risk older adults. However, it is well‐established that low mood is associated with SMC, leading to claims that memory concerns in older people may often reflect primarily psychological symptoms. This study aimed to determine the effect of low mood on subjective memory appraisal in older adults. Method We used a film‐based mood induction procedure (MIP) to test the effect of sad vs. neutral mood on subjective appraisal of memory performance in an experimental 2X2 between‐subjects design. Participants were 98 cognitively unimpaired older people (n=45 with SMC), randomised to the sad MIP (n=56) or the neutral MIP (n=42). All participants completed measures of trait SMC and ruminative self‐focused attention (RSFA) as well as perceived performance and metacognitive experience (ME) following the MIP and completion of a face‐name and a maze‐learning task. Result Participants in the sad MIP condition (M=42.75, SD=30.97) reported significantly greater sadness than those in the neutral condition following the manipulation (M=11.57, SD=18.44). The association between objective and subjective memory performance was stronger for cued recall on the face‐name task (r=.61, p=.001) and was weaker free recall on the face‐name task (r=.26, p=0.016) as well on the maze‐learning task (r=‐.16, p=.200). Contrary to expectation, there was no significant effect of mood condition on perceived performance on Face‐Name learning task (MD=‐2.43, p=498), but sad mood was associated with better perceived performance on the maze‐learning task (MD=13.34, p=.015). Results also indicated that RSFA and ME were implicated as mechanisms in subjective memory performance appraisal. Conclusion Findings indicate that SMC is a complex multifaceted phenomenon which may be underpinned by maladaptive self‐regulation and attentional systems, suggesting that psychological interventions may be appropriate for many older adults with SMC.
The Mediterranean diet and physical activity: A cross-sectional analysis of the Maintain Your Brain randomised controlled trial

Ghacham, A ; Noble, Y ; Rangel, CA ; Mavros, Y ; Radd-Vagenas, S ; Sabeti, N ; Heffernan, M ; Brodaty, H ; Sachdev, PS ; Lautenschlager, NT ; Singh, MAF ; O'Leary, F (Wiley, 2021-12-01)

BACKGROUND: Dementia has no pharmacological cure. Therefore, lifestyle interventions targeting modifiable risk factors to reduce cognitive decline are of interest. This study examines the cross-sectional relationships between two potentially protective behaviours: Mediterranean diet (MediDiet) adherence and physical activity (PA). METHOD: Participants were recruited from the Sax Institute's 45 and Up Study into the Maintain Your Brain trial. MediDiet adherence was assessed using the validated Mediterranean Diet and Culinary Index (MediCul) tool. The 50-item tool consists of 17 sub-categories focusing on key aspects of the MediDiet. Leisure time PA was assessed by a standard questionnaire and intensity was quantified using the BORG Rating of Perceived Exertion (RPE) scale, modified for strength and aerobic activities. Associations between the MediDiet and PA were investigated using hierarchical linear regression and analysis of covariance. RESULT: 6236 participants [55-77 years; mean (SD)=65.0 (5.8)] completed baseline assessments and were included. Mean (SD) MediCul score was 53.2 (13.0)/100), indicating low adherence to the MediDiet. Only 5% of participants achieved a score consistent with better cognitive outcomes in The PREDIMED study. Almost one-half of participants (48.4%) met aerobic PA (150 min/week) but less than one-quarter (24.2%) met resistance training (RT) recommendations (2 days/week). Unadjusted MediCul score explained a small but significant amount of the variance for light (1.0%) and moderate-vigorous (MV) (3.1%) PA, both p<0.001. For light PA, the final model, including MediCul, age, sex, BMI, CAGE (alcohol use) score and diabetes explained 2.8% of the variance. For MV PA, the final model including MediCul, age, sex, BMI, CAGE, depression, diabetes and education explained 10.9% of the variance. A 10-point higher MediCul score was associated with an additional 3.3 seconds of light PA/wk and additional 7.5 seconds of MV aerobic PA/wk (both p<0.001). Additionally, MediCul score was significantly higher in participants engaging in 2+days/wk of RT compared to 1 or fewer days/wk (56.6/100 vs. 52.2/100, respectively; p<0.001). CONCLUSION: Both aerobic and RT PA are significantly but weakly associated with better diet, but the clinical meaningfulness, as well as any causal nature, of these relationships requires further exploration. The outcomes of the MYB trial will contribute substantively to this question.
Lipidomic signatures for APOE genotypes provides new insights about mechanisms of resilience in Alzheimer’s disease

Wang, T ; Huynh, K ; Giles, C ; Lim, WLF ; Duong, T ; Mellett, NA ; Smith, A ; Olshansky, G ; Drew, BG ; Cadby, G ; Melton, PE ; Hung, J ; Beilby, J ; Watts, GF ; Chatterjee, P ; Martins, I ; Laws, SM ; Bush, AI ; Rowe, CC ; Villemagne, VL ; Ames, D ; Masters, CL ; Arnold, M ; Kastenmüller, G ; Nho, K ; Saykin, AJ ; Baillie, R ; Han, X ; Martins, RN ; Moses, E ; Kaddurah‐Daouk, RF ; Meikle, PJ (Wiley, 2021-12)

Background The apolipoprotein E gene (APOE) genotype is the first and strongest genetic risk factor for late‐onset Alzheimer’s disease and has emerged as a novel therapeutic target for AD. The encoded protein (Apolipoprotein E, APOE) is well‐known to be involved in lipoprotein transport and metabolism, but its effect on lipid metabolic pathways and the potential mediating effect of these on disease risk have not been fully defined. Method We performed lipidomic analysis on three independent cohorts (AIBL, n = 693; ADNI, n=207; BHS, n=4,384) and defined the association between APOE polymorphisms (ε4 and ε2) and plasma lipid species. To identify associations independent of lipoprotein metabolism, the analyses was performed with adjustment for clinical lipids (total cholesterol, HDL‐C and triglycerides). Causal mediation analysis was performed to estimate the proportion of risk in the outcome model explained by a direct effect of APOE genotype on prevalent AD — the average direct effect (ADE) — and the proportion that was mediated by lipid species or lipidomic risk models — the average causal mediation effect (ACME). Result We identified multiple associations of species from lipid classes such as ceramide, hexosylceramide, sphingomyelin, plasmalogens, alkyldiacylglycerol and cholesteryl esters with APOE polymorphisms (ε4 and ε2) that were independent of clinical lipoprotein measurements. There were 104 and 237 lipid species associated with APOE ε4 and ε2 respectively which were largely discordant. Of these 116 were also associated with Alzheimer’s disease. Individual lipid species (notably the alkyldiacylglycerol subspecies) or lipidomic risk models of APOE genotypes mediated up to 10% and 30% of APOE ε4 and ε2 treatment effect on AD risks respectively. Conclusion We demonstrate a strong relationship between APOE polymorphisms and peripheral lipid species. Lipids species mediate a proportion of the effects of APOE genotypes in risk of AD, particularly resilience with e2. Our results highlight the involvement of lipids in how APOE e2 mediates its resilience to AD and solidify their involvement with the disease pathway.
The effects of concurrent cognitive and meta-cognitive training on neuropsychiatric symptoms of people living with younger onset dementia: Protocol for a pilot trial

Sabates, JM ; Loi, SM ; Lautenschlager, NT ; Brodtmann, A ; Bahar-Fuchs, A (Wiley, 2021-12-01)

BACKGROUND: Neuropsychiatric symptoms (NPS) are behavioural and psychological disturbances frequent in people with dementia that have been linked with lower quality of life, lower cognitive functioning and greater caregiver distress, especially for caregivers of people with younger-onset dementia (YOD) (1). Several drug and non-drug treatments targeting NPS have been investigated in recent years. However, to the best of our knowledge, no treatment has been developed that concurrently targets and trains cognitive and meta-cognitive processes which are implicated in the expression of NPS. The aim of this pilot trial is to investigate the effects on NPS of a mobile application-based intervention simultaneously training both processes by incorporating elements of cognitive training and cognitive-behavioural therapy. METHOD: Twenty participants with YOD will be randomised to the training group or to a control group. Participants in the experimental condition will train at home three times a week for four weeks with remote therapist support. NPS, cognitive, psychological and caregiver outcomes will be assessed before and immediately after the intervention. RESULT: The mobile application is in the design stage and further studies are underway to incorporate the views of people with YOD and their care-partners, as well as clinicians, to the design. Recruitment of participants is expected in the second half of 2021. CONCLUSION: Findings from this trial will further our understanding of the utility of concurrently targeting cognitive and meta-cognitive processes in people with YOD when treating NPS and will inform a revision of the application. We believe that results from this study will have important implications for the management and treatment of NPS in the ever-growing field of interventions utilising technology. 1 Baillon, S., Gasper, A., Wilson-Morkeh, F., Pritchard, M., Jesu, A. and Velayudhan, L., 2019. Prevalence and Severity of Neuropsychiatric Symptoms in Early- Versus Late-Onset Alzheimer's Disease. American Journal of Alzheimer's Disease & Other Dementias®, 34(7-8), pp.433-438.
Maintain Your Brain trial: Early findings and lessons learned from adherence and compliance data

Brodaty, H ; Heffernan, M ; Anstey, KJ ; Fiatarone Singh, MA ; Jorm, L ; Lautenschlager, NT ; Maeder, A ; McNeil, J ; Sachdev, PS ; Valenzuela, M ; Chau, T (Wiley, 2021-12)

Background Technology and web‐based approaches potentially provide scalable population‐based interventions to reduce modifiable risk factors for dementia. Key issues in online interventions are recruitment and retention. To devise strategies to improve population reach We investigated which factors influence recruiting and maintaining participants in such an intervention, the in‐progress Maintain Your Brain trial. Method Invitations were sent to people aged 55‐77 years from the 45 and Up study, a population‐based cohort study of one in ten people aged 45 years and older in New South Wales, Australia (n = 267,000). For MYB, participants were required to be eligible for at least one of four modules to be enrolled (physical activity, nutrition, brain training and mental wellbeing). All participants received modules based on their risks and were randomly allocated to either personalised coaching (intervention) or static information (control). Associations between participant characteristics (listed Table 1) and likelihood of completing set assessment tasks was assessed at two key stages – end of baseline and end of 12‐month follow‐up using stepwise (forward) regression. Results Of 96,418 people invited, 12,281 (13%) participants started baseline and completed a mean of 6.2 (SD 4.3) of ten assessments. Of these, 6,236 (6%) were enrolled in the trial. At 12‐months participants completed a mean of 5.0 of 8 assessments (SD = 3.8). Completion rate of the primary outcome (two tasks) was 62% (3,869). In the final regression model for baseline (Table1), overall associations were weak even though statistically significant, with only years of education not entered in the final model. The follow‐up model included retirement status, gender, baseline dementia risk and baseline wellbeing. However, this model (df1 = 1, df2 =6231; R2 = .01) accounted for even less variation than baseline model (R2 = .04). Conclusion Overall, regression models of participant characteristics accounted for a low amount of variation in task completion rates at both baseline and follow‐up. Participants were less likely to complete baseline tasks if they were older, male, not living with a spouse or alone and not retired or had lower dementia risk score and more psychological distress.
Association of the Mediterranean diet with cognition in a Western population

Sabeti, N ; O'Leary, F ; Flood, VM ; Valenzuela, M ; Radd‐Vagenas, S ; Noble, Y ; Rangel, CA ; Gracham, A ; Heffernan, M ; Sachdev, PS ; Brodaty, H ; Lautenschlager, NT ; Singh, MAF (Wiley, 2021-12)

Background The Mediterranean‐style diet (MD) is promoted as one of the healthiest dietary patterns and has been shown to reduce cognitive decline in some randomised controlled trials (RCTs). This pattern is plant‐based with a focus on vegetables, legumes, fish, and olive oil, with low intake of red meats and foods high in sugar and saturated fats. The Maintain Your Brain (MYB) study is an online multi‐domain RCT targeting modifiable risk factors for dementia, including diet. This study investigated cross‐sectional associations between adherence to a MD pattern and cognition. Methods Participants enrolled in MYB were recruited from the Sax Institute’s larger 45 and Up Study, and included those with all baseline MYB assessments (n=6236). Diet was assessed using the validated Mediterranean Diet and Culinary Index tool. This 50‐item tool assesses intake of nine desirable and four undesirable features of the MD diet and allows derivation of the Mediterranean Diet Adherence Screener (MEDAS). Computerised cognitive tests, administered through the MYB digital platform, were used to assess domains of executive function, complex attention, learning and memory and global cognition. Results Participants were 46% male, with mean (SD) age 65.0 (5.8) years, BMI 26.6 (4.9) kg/m2 and well educated (46% with tertiary education). Higher MEDAS scores were associated with being female, younger, better educated and having a lower BMI (all p<0.001). Overall participant adherence to a MD pattern was low; MEDAS score 6.1 (2.1)/14. After covariate adjustment and correction for multiple analyses in hierarchical linear regression models, better MEDAS scores were significantly associated with worse (lower) z‐scores for executive function (β ‐0.018, p=0.003). For every 1‐point higher MEDAS score, executive function z‐scores were 0.018 lower. This unexpected negative association was clinically very small. There were no significant associations with other cognitive domains. Conclusion Adherence to a MD was sub‐optimal in this well‐educated Australian sample. The one unexpected finding is likely not clinically meaningful given its size. Additionally, as this was a cross‐sectional study, reverse causality cannot be ruled out. Results from the main MYB RCT will provide data on MD acceptance and impact in a Western dietary environment.
Dynamics between Neuropsychiatric Symptoms and Biomarkers: A Pilot Study

Chiu, W ; Goh, AMY ; Velakoulis, D ; Loi, SM (Wiley, 2021-12)

Background The aetiology of neuropsychiatric symptoms (NPS) in dementia remains unclear, and currently, it is challenging to distinguish neuropsychiatric manifestations related to younger‐onset neurodegenerative diseases from those of primary psychiatric disorders. Neurofilament light chain (NfL) is a promising biomarker for axonal injury and has been found to differentiate between neurodegenerative diseases and primary psychiatric disorders. The aim was to investigate cerebrospinal fluid (CSF) NfL and its relationship with NPS and compare it with traditional biomarkers, namely Aβ and tau. Methods Retrospective data for 54 patients with younger‐onset dementia was collated (mean age ± SD, 57.9 ± 7.1, females n = 15 [28%], co‐morbid psychiatric diagnoses n = 17 [31%]). Of these, 23 had Alzheimer’s disease (AD), 14 had frontotemporal dementia (FTD), 9 had mild cognitive impairment (MCI), and 8 were diagnosed with other types of dementia. Neuropsychiatric measures were extracted from the Neuropsychiatry Unit Cognitive Assessment Tool (NUCOG), the Depression Anxiety and Stress Scale 21 (DASS‐21), and the revised Cambridge Behavioural Inventory (CBI‐R). CSF biomarkers included NfL, Ab‐42, p‐tau and t‐tau. Results No significant associations between NPS and NfL was seen in patients with AD, FTD, MCI or other diagnoses. In the combined cohort, a positive correlation was found between the overall cognitive functioning and Ab‐42 levels (r = 0.47, p = 0.01), and visuoconstruction, a specific domain of cognitive functioning, was found to be positively correlated with Ab‐42 levels (r = 0.44, p = 0.03) and negatively correlated with t‐tau levels (r = ‐0.43, p = 0.03). In FTD, a positive correlation was found between stress and p‐tau levels (n = 8, r = 0.89, p = 0.04), and this correlation was stronger in patients without co‐morbid psychiatric diagnoses (n = 7, r = 0.93, p = 0.03). Conclusion The results suggest that levels of CSF biomarkers, especially Ab‐42, are linked to deficits in cognitive functioning in patients with younger‐onset dementia, and levels of p‐tau are strongly related to stress particularly in the absence of co‐morbid psychiatric diagnoses. Therefore, these biomarkers may assist in the identification of patients who are at an increased risk of developing cognitive impairment and stress.
The dementia policies in Australia relating to the COVID‐19 pandemic

Goh, AMY ; Dow, B (Wiley, 2021-12)

Background Australia has a population of 26 million, and on January 28th 2021, 28,794 COVID‐19 infections and 909 deaths. 685 deaths were at residential aged care facilities, and data from the Australian Bureau of Statistics revealed that 72.7% of the people who died of the coronavirus in Australia (up to 31 August 2020) had at least one pre‐existing chronic condition listed on their death certificate, with dementia the most common (noted on 41% of death certificates). This presentation will present and discuss the key Australian dementia policy interventions implemented during the pandemic. Method A scoping review of published academic, media, policy papers, white papers, and grey literature was conducted. We extracted relevant information pertaining to policies relating to dementia care during the COVID‐19 pandemic. Result The Australian government is managing the COVID‐19 outbreak as a health emergency, and have developed and funded a comprehensive response. For the older population and those with ADRD, the key policies include the National Health Plans, specific plans for people with disabilities, telehealth expansions, mental health and wellbeing pandemic response plans, home delivery of prescriptions, the establishment of an Aged Care Health Emergency Response Operations Centre, and a National COVID‐19 Aged Care Plan. In Victoria, the Victorian Aged Care Response Centre was established. The Pfizer/BioNTech vaccine will be given to priority groups from February 2021, which include aged care and disability care residents and workers (people with dementia account for 52% of all residents in aged care facilities). Strict policies were put in place for aged care facility visitations, and for the aged care workforce, such as the use of personal protective equipment and limiting staff to work in only one facility. Advocacy bodies were also key, and Dementia Australia and Dementia Support Australia, for example, developed advice to support people experiencing behavioural and psychological symptoms of dementia during the pandemic. Conclusion There are currently no active cases in residential aged care in Australia, zero locally acquired cases for several weeks, with the (minimal) new cases emerging from the hotel quarantine system. Health policies have managed to limit the spread of COVID‐19 infection in Australia.
Higher coffee consumption is associated with slower cognitive decline and Aβ‐amyloid accumulation over 126 months: Data from the AIBL study

Gardener, SL ; Rainey‐Smith, SR ; Villemagne, VLL ; Fripp, J ; Dore, V ; Bourgeat, P ; Taddei, K ; Masters, CL ; Maruff, PT ; Rowe, CC ; Ames, D ; Martins, RN (Wiley, 2021-12)

Background Worldwide, coffee is one of the most popular beverages consumed. Several studies have suggested a protective role of coffee, including reduced risk of Alzheimer’s disease (AD). However, there is limited longitudinal data available in cohorts of older adults reporting associations of coffee intake with cognitive decline, in distinct domains, and investigating the neuropathological mechanisms underpinning these associations. Method The aim of the current study was to investigate the relationship between self‐reported baseline coffee intake (mean = 280 ± 323 g/day) and cognitive decline assessed using a comprehensive neuropsychological battery, over 126 months, in 227 cognitively normal individuals from the Australian Imaging, Biomarkers, and Lifestyle (AIBL) study. We also sought to investigate the relationship between coffee intake and cerebral Aβ‐amyloid accumulation and brain volumes in a subset of individuals (n=60; and n=51, respectively) over 126 months. Result Higher baseline coffee consumption was associated with slower cognitive decline in executive function, attention, and the AIBL Preclinical AD Cognitive Composite (PACC; shown to reliably measure the first signs of cognitive decline in at‐risk cognitively normal populations) over 126 months. Higher baseline coffee consumption was also associated with slower Aβ‐amyloid accumulation over 126 months, and lower risk of transitioning from ‘negative’ Aβ‐amyloid status to ‘moderate’, and ‘very high’ Aβ‐amyloid burden over the same time period. There were no associations between coffee intake and atrophy in total grey matter, white matter, or hippocampal volume. Conclusion Our results further support the hypothesis that coffee intake may be a protective factor against AD, with increased coffee consumption reducing cognitive decline potentially by slowing cerebral Aβ‐amyloid accumulation, and thus attenuating the associated neurotoxicity from Aβ‐amyloid‐mediated oxidative stress and inflammatory processes. Further investigation is required to evaluate how coffee intake could be incorporated as one modifiable lifestyle factor aimed at delaying AD onset.
How lifestyle shapes the brain: Associations between physical activity, sleep, beta‐amyloid and cognitive function in older adults

Sewell, KR ; Rainey‐Smith, SR ; Villemagne, VLL ; Peiffer, JJ ; Sohrabi, HR ; Taddei, K ; Ames, D ; Maruff, PT ; Laws, SM ; Masters, CL ; Rowe, CC ; Martins, RN ; Erickson, KI ; Brown, BM (Wiley, 2021-12)

Abstract Background Lifestyle factors such as sleep and physical activity influence risk of cognitive decline and dementia. Higher habitual physical activity and optimal sleep are associated with better cognitive function and lower levels of Alzheimer’s disease biomarkers, including beta‐amyloid (Aß). There is currently a poor understanding of how physical activity may influence the relationship between sleep and cognition, and whether exercise and sleep interact to influence cognition and Aß. Developing this understanding is crucial for creating effective lifestyle interventions for dementia prevention. Method Data from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study were utilised to determine whether self‐reported physical activity moderates the cross‐sectional relationship between self‐reported sleep parameters (duration, efficiency, latency, disturbance, quality), cognitive function (episodic memory, attention and processing speed, executive function), and brain Aß (quantified by amyloid positron emission tomography, using the Centiloid scale). Analyses were adjusted for age, sex, APOE ε4 carriage, mood, premorbid intelligence, and collection point. Participants were 404 community‐dwelling cognitively normal older adults aged 60 and above (75.3 5.7 years). Data from a subset of participants (n = 220, aged 75.2 5.6 years) were used for analyses with AB as the outcome. Result Physical activity moderated the relationship between sleep duration and episodic memory (ß = ‐.09, SE = .03, p = .005), and sleep efficiency and episodic memory (ß = ‐.08, SE = .03, p = .016). Physical activity moderated the relationship between sleep duration and A® (ß = ‐.12, SE = .06, p = .036), and sleep quality and Aß (ß = .12, SE = .06, p = .029). Conclusion Physical activity may play an important role in the relationship between sleep and cognitive function, and sleep and brain Aß. Future longitudinal and intervention studies in this area are crucial for informing interventions for dementia prevention.

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