Psychiatry - Research Publications

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    A Randomized Controlled Trial on the Effects of a 6-Month Home-Based Physical Activity Program with Individual Goal-Setting and Volunteer Mentors on Physical Activity, Adherence, and Physical Fitness in Inactive Older Adults at Risk of Cognitive Decline: The INDIGO Study
    Cox, KL ; Clare, L ; Cyarto, E ; Ellis, KA ; Etherton-Beer, C ; Southam, J ; Ames, D ; Flicker, L ; Almeida, OP ; LoGiudice, D ; Liew, D ; Vlaskovsky, P ; Lautenschlager, NT ; Hauer, K (IOS PRESS, 2021-01-01)
    BACKGROUND: Increasing physical activity (PA) in those who have memory concerns requires innovative approaches. OBJECTIVE: To compare in this randomized controlled trial (RCT) the effects on PA, adherence, and fitness of two approaches to deliver a 6-month home-based PA program in older, inactive individuals at risk of cognitive decline. METHODS: Individuals (n = 52) aged 60-85 years, inactive with mild cognitive impairment or subjective cognitive decline were recruited from the community and memory clinics. Randomization was to 6 months of 150 min/week moderate intensity PA with either: goal-setting with mentor support; or education and peer contact. A subset of participants (n = 36) continued for a further 6 months. PA, moderate and vigorous PA, and secondary outcomes, fitness, goal performance/satisfaction and self-efficacy were assessed at baseline, 6 and 12 months. Modelling of primary and secondary outcomes was conducted with linear mixed models. RESULTS: Participants were mean age (±sd) 70.1 (6.4) years. Six-month retention was 88.5%(n = 46). No significant between-group differences were observed for PA or fitness. Post-hoc combined group data showed a significant, moderate-large effect size increase in PA with time. PA increased by a mean 1,662 (943, 2383) steps/day (95%CI) and 1,320 (603, 2037) steps/day at 6 and 12 months (p < 0.001). Median (quartiles Q1-Q3) 6 and 6-12 month combined group adherence was 88.9 (74.4-95.7)%and 84.6 (73.9-95.4)%respectively. CONCLUSION: In this target group, no differences were detected between groups both intervention strategies were highly effective in increasing PA and fitness.
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    Assessment of the DTI-ALPS Parameter Along the Perivascular Space in Older Adults at Risk of Dementia
    Steward, CE ; Venkatraman, VK ; Lui, E ; Malpas, CB ; Ellis, KA ; Cyarto, EV ; Vivash, L ; O'Brien, TJ ; Velakoulis, D ; Ames, D ; Masters, CL ; Lautenschlager, NT ; Bammer, R ; Desmond, PM (WILEY, 2021-02-08)
    BACKGROUND AND PURPOSE: Recently, there has been growing interest in the glymphatic system (the functional waste clearance pathway for the central nervous system and its role in flushing solutes (such as amyloid ß and tau), metabolic, and other cellular waste products in the brain. Herein, we investigate a recent potential biomarker for glymphatic activity (the diffusion tensor imaging along the perivascular space [DTI-ALPS] parameter) using diffusion MRI imaging in an elderly cohort comprising 10 cognitively normal, 10 mild cognitive impairment (MCI), and 16 Alzheimer's disease (AD). METHODS: All 36 participants imaged on a Siemens 3.0T Tim Trio. Single-SE diffusion weighted Echo-planar imaging scans were acquired as well as T1 magnetization prepared rapid gradient echo, T2 axial, and susceptibility weighted imaging. Three millimeter regions of interest were drawn in the projection and association fibers adjacent to the medullary veins at the level of the lateral ventricle. The DTI-ALPS parameter was calculated in these regions and correlated with cognitive status, Mini-Mental State Examination (MMSE), and ADASCog11 measures. RESULTS: Significant correlations were found between DTI-ALPS and MMSE and ADASCog11 in the right hemisphere adjusting for age, sex, and APoE ε4 status. Significant differences were also found in the right DTI-ALPS indices between cognitively normal and AD groups (P < .026) and MCI groups (P < .025) in a univariate general linear model corrected for age, sex, and APoE ε4. Significant differences in apparent diffusion coefficient between cognitively normal and AD groups were found in the right projection fibers (P = .028). CONCLUSION: Further work is needed to determine the utility of DTI-ALPS index in larger elderly cohorts and whether it measures glymphatic activity.
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    The Support Person's Preferences and Perspectives of Physical Activity Programs for Older Adults With Cognitive Impairment
    Chong, TWH ; You, E ; Ellis, KA ; Cox, KL ; Harrington, KD ; Rainey-Smith, SR ; Ames, D ; Lautenschlager, NT (FRONTIERS MEDIA SA, 2021-09-23)
    Objectives: Physical activity (PA) is beneficial for older adults' cognition. There is limited research investigating perspectives of support persons (SPs) of next-of-kins (NOKs) with cognitive impairment. This exploratory study aimed to investigate perspectives of SPs of older adults with Alzheimer's Dementia (AD) or Mild Cognitive Impairment (MCI). Methods: A telephone survey of 213 SPs of NOKs from the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing (AIBL) was undertaken to quantitatively assess SPs' beliefs and knowledge about PA benefits, current PA level of their NOK, and PA program preferences. The contribution of age, gender, diagnosis and mental health symptoms was assessed using multiple logistic regression analyses. Results: Many SPs were aware of PA benefits for memory (64%) and believed it would help their NOK (72%). Older SP age was associated with less awareness of benefits (p = 0.016). SPs caring for male NOKs were more likely to believe that PA would be helpful than those caring for female NOKs (p = 0.049). NOK AD diagnosis (rather than MCI) (p = 0.014), older age (p = 0.005) and female gender (p = 0.043) were associated with lower PA levels. SPs were mixed regarding preference for their NOKs to participate in individual (45%) or group (54%) PA. Many SPs wanted to participate in PA with their NOK (63%). Conclusions: The results highlight that SPs have high levels of awareness of the cognitive benefits of PA, and describe their preferences regarding PA programs. The findings provide new information to inform targeted public health messaging, PA prescribers and providers, and future research directions.
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    Trajectories of depressive and anxiety symptoms in older adults: a 6-year prospective cohort study
    Holmes, SE ; Esterlis, I ; Mazure, CM ; Lim, YY ; Ames, D ; Rainey-Smith, S ; Fowler, C ; Ellis, K ; Martins, RN ; Salvado, O ; Dore, V ; Villemagne, VL ; Rowe, CC ; Laws, SM ; Masters, CL ; Pietrzak, RH ; Maruff, P (WILEY, 2018-02-01)
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    Cerebrovascular disease, Alzheimer's disease biomarkers and longitudinal cognitive decline
    Yates, PA ; Villemagne, VL ; Ames, D ; Masters, CL ; Martins, RN ; Desmond, P ; Burnham, S ; Maruff, P ; Ellis, KA ; Rowe, CC (WILEY-BLACKWELL, 2016-06-01)
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    Why attend a memory clinic? What do patients and their families want and/or expect?
    Mastwyk, M ; Dow, B ; Ellis, KA ; Ames, D (WILEY, 2016-09-01)
    OBJECTIVE: To explore which symptoms led people to seek a memory clinic assessment and what they wanted and expected from that assessment. Did the patient and family want and/or expect diagnostic disclosure and, if so, why? METHODS: Patients scheduled for memory clinic appoint-ments received two questionnaires by post prior to clinic attendance - one for the patient, one for the next-of- kin - regarding symptomatology, wants, expectations and rationale. RESULTS: Ninety-two per cent of patients (n = 47) and 88% (n = 43) of next-of-kin wanted the patient to be informed of the diagnosis; 84% (n = 43) of patients and 86% (n = 42) of next-of-kin expected the patient to be informed. Rationales for diagnostic disclosure were categorised under themes of planning, treatment, information, coping strategies and rights. CONCLUSIONS: Patients and families want diagnostic disclosure in order to plan, receive treatment, receive help and learn strategies to cope. This knowledge is seen as the patient's right.
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    Fifteen Years of the Australian Imaging, Biomarkers and Lifestyle (AIBL) Study: Progress and Observations from 2,359 Older Adults Spanning the Spectrum from Cognitive Normality to Alzheimer's Disease
    Fowler, C ; Rainey-Smith, SR ; Bird, S ; Bomke, J ; Bourgeat, P ; Brown, BM ; Burnham, SC ; Bush, A ; Chadunow, C ; Collins, S ; Doecke, J ; Dore, V ; Ellis, KA ; Evered, L ; Fazlollahi, A ; Fripp, J ; Gardener, SL ; Gibson, S ; Grenfell, R ; Harrison, E ; Head, R ; Jin, L ; Kamer, A ; Lamb, F ; Lautenschlager, NT ; Laws, SM ; Li, Q-X ; Lim, L ; Lim, YY ; Louey, A ; Macaulay, SL ; Mackintosh, L ; Martins, RN ; Maruff, P ; Masters, CL ; McBride, S ; Milicic, L ; Peretti, M ; Pertile, K ; Porter, T ; Radler, M ; Rembach, A ; Robertson, J ; Rodrigues, M ; Rowe, CC ; Rumble, R ; Salvado, O ; Savage, G ; Silbert, B ; Soh, M ; Sohrabi, HR ; Taddei, K ; Taddei, T ; Thai, C ; Trounson, B ; Tyrrell, R ; Vacher, M ; Varghese, S ; Villemagne, VL ; Weinborn, M ; Woodward, M ; Xia, Y ; Ames, D (IOS PRESS, 2021-01-01)
    BACKGROUND: The Australian Imaging, Biomarkers and Lifestyle (AIBL) Study commenced in 2006 as a prospective study of 1,112 individuals (768 cognitively normal (CN), 133 with mild cognitive impairment (MCI), and 211 with Alzheimer's disease dementia (AD)) as an 'Inception cohort' who underwent detailed ssessments every 18 months. Over the past decade, an additional 1247 subjects have been added as an 'Enrichment cohort' (as of 10 April 2019). OBJECTIVE: Here we provide an overview of these Inception and Enrichment cohorts of more than 8,500 person-years of investigation. METHODS: Participants underwent reassessment every 18 months including comprehensive cognitive testing, neuroimaging (magnetic resonance imaging, MRI; positron emission tomography, PET), biofluid biomarkers and lifestyle evaluations. RESULTS: AIBL has made major contributions to the understanding of the natural history of AD, with cognitive and biological definitions of its three major stages: preclinical, prodromal and clinical. Early deployment of Aβ-amyloid and tau molecular PET imaging and the development of more sensitive and specific blood tests have facilitated the assessment of genetic and environmental factors which affect age at onset and rates of progression. CONCLUSION: This fifteen-year study provides a large database of highly characterized individuals with longitudinal cognitive, imaging and lifestyle data and biofluid collections, to aid in the development of interventions to delay onset, prevent or treat AD. Harmonization with similar large longitudinal cohort studies is underway to further these aims.
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    Association Between Cognitive Function and Clustered Cardiovascular Risk of Metabolic Syndrome in Older Adults at Risk of Cognitive Decline
    Lai, MMY ; Ames, DJ ; Cox, KL ; Ellis, KA ; Sharman, MJ ; Hepworth, G ; Desmond, P ; Cyarto, E ; Szoeke, C ; Martins, R ; Masters, CL ; Lautenschlager, NT (SPRINGER FRANCE, 2020-02-11)
    OBJECTIVES: Metabolic syndrome (MetS) represents a cluster of obesity and insulin resistance-related comorbidities. Abdominal obesity, hypertension, elevated triglyceride and glucose levels are components of MetS and may have a negative effect on cognitive function, but few cognitive studies have examined the combined risk severity. We sought to determine which specific cognitive abilities were associated with MetS in older adults at risk of cognitive decline. DESIGN: Cross-sectional study. PARTICIPANTS: 108 AIBL Active participants with memory complaints and at least one cardiovascular risk factor. MEASUREMENTS: Cardiovascular parameters and blood tests were obtained to assess metabolic syndrome criteria. The factors of MetS were standardized to obtain continuous z-scores. A battery of neuropsychological tests was used to evaluate cognitive function. RESULTS: Higher MetS z-scores were associated with poorer global cognition using ADAS-cog (adjusted standardized beta=0.26, SE 0.11, p<0.05) and higher Trail Making B scores (adjusted beta=0.23, SE 0.11, p<0.05). Higher MetS risk was related to lower cognitive performance. CONCLUSION: Combined risk due to multiple risk factors in MetS was related to lower global cognitive performance and executive function. A higher MetS risk burden may point to opportunities for cognitive testing in older adults as individuals may experience cognitive changes.
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    Association of Plasma A beta Peptides with Blood Pressure in the Elderly
    Lambert, J-C ; Dallongeville, J ; Ellis, KA ; Schraen-Maschke, S ; Lui, J ; Laws, S ; Dumont, J ; Richard, F ; Cottel, D ; Berr, C ; Ames, D ; Masters, CL ; Rowe, CC ; Szoeke, C ; Tzourio, C ; Dartigues, J-F ; Buee, L ; Martins, R ; Amouyel, P ; Gravenor, MB (PUBLIC LIBRARY SCIENCE, 2011-04-15)
    BACKGROUND: Aß peptides are often considered as catabolic by-products of the amyloid ß protein precursor (APP), with unknown physiological functions. However, several biological properties have been tentatively attributed to these peptides, including a role in vasomotion. We assess whether plasma Aß peptide levels might be associated with systolic and diastolic blood pressure values (SBP and DBP, respectively). METHODOLOGY/PRINCIPAL FINDINGS: Plasma Aß(1-40) and Aß(1-42) levels were measured using an xMAP-based assay in 1,972 individuals (none of whom were taking antihypertensive drugs) from 3 independent studies: the French population-based 3C and MONA-LISA (Lille) studies (n = 627 and n = 769, respectively) and the Australian, longitudinal AIBL study (n = 576). In the combined sample, the Aß(1-42)/ Aß(1-40) ratio was significantly and inversely associated with SBP (p = 0.03) and a similar trend was observed for DBP (p = 0.06). Using the median age (69) as a cut-off, the Aß(1-42)/Aß(1-40) ratio was strongly associated with both SBP and DBP in elderly individuals (p = 0.002 and p = 0.03, respectively). Consistently, a high Aß(1-42)/ Aß(1-40) ratio was associated with a lower risk of hypertension in both the combined whole sample (odds ratio [OR], 0.71; 95% confidence interval [CI], 0.56-0.90) and (to an even greater extent) in the elderly subjects (OR, 0.53; 95% CI, 0.37-0.75). Lastly, all these associations appeared to be primarily driven by the level of plasma Aß(1-40). CONCLUSION: The plasma Aß(1-42)/Aß(1-40) ratio is inversely associated with SBP, DBP and the risk of hypertension in elderly subjects, suggesting that Aß peptides affect blood pressure in vivo. These results may be particularly relevant in Alzheimer's disease, in which a high Aß(1-42)/Aß(1-40) plasma ratio is reportedly associated with a decreased risk of incident disease.
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    APOE and BDNF polymorphisms moderate amyloid beta-related cognitive decline in preclinical Alzheimer's disease
    Lim, YY ; Villemagne, VL ; Laws, SM ; Pietrzak, RH ; Snyder, PJ ; Ames, D ; Ellis, KA ; Harrington, K ; Rembach, A ; Martins, RN ; Rowe, CC ; Masters, CL ; Maruff, P (NATURE PUBLISHING GROUP, 2015-11-01)
    Accumulation of β-amyloid (Aβ) in the brain is associated with memory decline in healthy individuals as a prelude to Alzheimer's disease (AD). Genetic factors may moderate this decline. We examined the role of apolipoprotein E (ɛ4 carrier[ɛ4(+)], ɛ4 non-carrier[ɛ4(-)]) and brain-derived neurotrophic factor (BDNF(Val/Val), BDNF(Met)) in the extent to which they moderate Aβ-related memory decline. Healthy adults (n=333, Mage=70 years) enrolled in the Australian Imaging, Biomarkers and Lifestyle study underwent Aβ neuroimaging. Neuropsychological assessments were conducted at baseline, 18-, 36- and 54-month follow-ups. Aβ positron emission tomography neuroimaging was used to classify participants as Aβ(-) or Aβ(+). Relative to Aβ(-)ɛ4(-), Aβ(+)ɛ4(+) individuals showed significantly faster rates of cognitive decline over 54 months across all domains (d=0.40-1.22), while Aβ(+)ɛ4(-) individuals showed significantly faster decline only on verbal episodic memory (EM). There were no differences in rates of cognitive change between Aβ(-)ɛ4(-) and Aβ(-)ɛ4(+) groups. Among Aβ(+) individuals, ɛ4(+)/BDNF(Met) participants showed a significantly faster rate of decline on verbal and visual EM, and language over 54 months compared with ɛ4(-)/BDNF(Val/Val) participants (d=0.90-1.02). At least two genetic loci affect the rate of Aβ-related cognitive decline. Aβ(+)ɛ4(+)/BDNF(Met) individuals can expect to show clinically significant memory impairment after 3 years, whereas Aβ(+)ɛ4(+)/BDNF(Val/Val) individuals can expect a similar degree of impairment after 10 years. Little decline over 54 months was observed in the Aβ(-) and Aβ(+) ɛ4(-) groups, irrespective of BDNF status. These data raise important prognostic issues in managing preclinical AD, and should be considered in designing secondary preventative clinical trials.