Psychiatry - Research Publications

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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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    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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    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.
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    Alterations in dorsal and ventral posterior cingulate connectivity in APOE epsilon 4 carriers at risk of Alzheimer's disease
    Kerestes, R ; Phal, PM ; Steward, C ; Moffat, BA ; Salinas, S ; Cox, KL ; Ellis, KA ; Cyarto, EV ; Ames, D ; Martins, RN ; Masters, CL ; Rowe, CC ; Sharman, MJ ; Salvado, O ; Szoeke, C ; Lai, M ; Lautenschlager, NT ; Desmond, PM (ROYAL COLL PSYCHIATRISTS, 2015-10-01)
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    A 'Disease Severity Index' to identify individuals with Subjective Memory Decline who will progress to mild cognitive impairment or dementia
    Ferreira, D ; Falahati, F ; Linden, C ; Buckley, RF ; Ellis, KA ; Savage, G ; Villemagne, VL ; Rowe, CC ; Ames, D ; Simmons, A ; Westman, E (NATURE PUBLISHING GROUP, 2017-03-13)
    Subjective memory decline (SMD) is a heterogeneous condition. While SMD might be the earliest sign of Alzheimer's disease (AD), it also occurs in aging and various neurological, medical, and psychiatric conditions. Identifying those with higher risk to develop dementia is thus a major challenge. We tested a novel disease severity index generated by multivariate data analysis with numerous structural MRI measures as input. The index was used to identify SMD individuals with high risk of progression to mild cognitive impairment (MCI) or AD. A total of 69 healthy controls, 86 SMD, 45 MCI, and 38 AD patients were included. Subjects were followed up for 7.5 years. Clinical, cognitive, PET amyloid imaging and APOE ε4 data were used as outcome variables. The results showed that SMD evidenced cognitive performance intermediate between healthy controls and MCI. The disease severity index identified eleven (13%) SMD individuals with an AD-like pattern of brain atrophy. These individuals showed lower cognitive performance, increased CDR-SOB, higher amyloid burden and worse clinical progression (6.2 times higher likelihood to develop MCI, dementia or die than healthy controls). The current disease severity index may have relevance for clinical practice, as well as for selecting appropriate individuals for clinical trials.
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    A Randomized Controlled Trial of Adherence to a 24-Month Home-Based Physical Activity Program and the Health Benefits for Older Adults at Risk of Alzheimer's Disease: The AIBL Active-Study
    Cox, KL ; Cyarto, E ; Ellis, KA ; Ames, D ; Desmond, P ; Phal, P ; Sharman, MJ ; Szoeke, C ; Rowe, CC ; Masters, CL ; You, E ; Burrows, S ; Lai, MMY ; Lautenschlager, NT ; Anstey, K ; Peters, R (IOS PRESS, 2019-01-01)
    BACKGROUND: Previous studies have demonstrated that physical activity (PA) interventions can improve physical and cognitive outcomes in older adults, but most have been relatively short in duration (<1 year) with a few having specifically targeting individuals at risk of developing Alzheimer's disease. OBJECTIVE: To examine adherence and physical health outcomes in a 24-month home-based PA intervention in older adults at risk of Alzheimer's disease. METHODS: Participants 60 years and older with mild cognitive impairment (MCI) or subjective memory complaints (SMC) with at least 1 cerebrovascular risk factor recruited from The Australian Imaging Biomarkers and Lifestyle Flagship Study of Aging (AIBL) were randomized to a PA or control group (n = 106). The control group continued with their usual lifestyle. The PA group received a 24-month home-based program with a target of 150 minutes/week of moderate PA and a behavioral intervention. Retention (participants remaining) and PA adherence (PA group only, percent PA completed to the PA prescribed) were determined at 6, 12, 18, and 24 months. Assessments at baseline, 6, 12, and 24 months included, PA; fitness; body composition and fat distribution. Key outcome measures were PA adherence and PA. RESULTS: The 24-month retention rate (97.2%) and the median PA adherence 91.67% (Q1-Q3, 81.96, 100.00) were excellent. In the long-term the intervention group achieved significantly better improvements in PA levels, leg strength, fat mass and fat distribution compared to the control. CONCLUSION: This study demonstrates that in this target group, long-term PA adherence is achievable and has physical health benefits.
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    Influence of BDNF Val66Met on the relationship between physical activity and brain volume
    Brown, BM ; Bourgeat, P ; Peiffer, JJ ; Burnham, S ; Laws, SM ; Rainey-Smith, SR ; Bartres-Faz, D ; Villemagne, VL ; Taddei, K ; Rembach, A ; Bush, A ; Ellis, KA ; Macaulay, SL ; Rowe, CC ; Ames, D ; Masters, CL ; Maruff, P ; Martins, RN (LIPPINCOTT WILLIAMS & WILKINS, 2014-10-07)
    OBJECTIVE: To investigate the association between habitual physical activity levels and brain temporal lobe volumes, and the interaction with the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism. METHODS: This study is a cross-sectional analysis of 114 cognitively healthy men and women aged 60 years and older. Brain volumes quantified by MRI were correlated with self-reported physical activity levels. The effect of the interaction between physical activity and the BDNF Val66Met polymorphism on brain structure volumes was assessed. Post hoc analyses were completed to evaluate the influence of the APOE ε4 allele on any found associations. RESULTS: The BDNF Val66Met polymorphism interacted with physical activity to be associated with hippocampal (β = -0.22, p = 0.02) and temporal lobe (β = -0.28, p = 0.003) volumes. In Val/Val homozygotes, higher levels of physical activity were associated with larger hippocampal and temporal lobe volumes, whereas in Met carriers, higher levels of physical activity were associated with smaller temporal lobe volume. CONCLUSION: The findings from this study support higher physical activity levels in the potential attenuation of age- and disease-related hippocampal and temporal lobe volume loss in Val/Val homozygotes.
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    A plasma protein classifier for predicting amyloid burden for preclinical Alzheimer's disease
    Ashton, NJ ; Nevado-Holgado, AJ ; Barber, IS ; Lynham, S ; Gupta, V ; Chatterjee, P ; Goozee, K ; Hone, E ; Pedrini, S ; Blennow, K ; Scholl, M ; Zetterber, H ; Ellis, KA ; Bush, A ; Rowe, CC ; Villemagne, VL ; Ames, D ; Masters, CL ; Aarsland, D ; Powell, J ; Lovestone, S ; Martins, R ; Hye, A (AMER ASSOC ADVANCEMENT SCIENCE, 2019-02-01)
    A blood-based assessment of preclinical disease would have huge potential in the enrichment of participants for Alzheimer's disease (AD) therapeutic trials. In this study, cognitively unimpaired individuals from the AIBL and KARVIAH cohorts were defined as Aβ negative or Aβ positive by positron emission tomography. Nontargeted proteomic analysis that incorporated peptide fractionation and high-resolution mass spectrometry quantified relative protein abundances in plasma samples from all participants. A protein classifier model was trained to predict Aβ-positive participants using feature selection and machine learning in AIBL and independently assessed in KARVIAH. A 12-feature model for predicting Aβ-positive participants was established and demonstrated high accuracy (testing area under the receiver operator characteristic curve = 0.891, sensitivity = 0.78, and specificity = 0.77). This extensive plasma proteomic study has unbiasedly highlighted putative and novel candidates for AD pathology that should be further validated with automated methodologies.
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    A randomized controlled trial of physical activity with individual goal-setting and volunteer mentors to overcome sedentary lifestyle in older adults at risk of cognitive decline: the INDIGO trial protocol
    Cox, KL ; Cyarto, EV ; Etherton-Beer, C ; Ellis, KA ; Alfonso, H ; Clare, L ; Liew, D ; Ames, D ; Flicker, L ; Almeida, OP ; LoGiudice, D ; Lautenschlager, NT (BMC, 2017-09-13)
    BACKGROUND: Increasing physical activity (PA) effectively in those who are inactive is challenging. For those who have subjective memory complaints (SMC) or mild cognitive impairment (MCI) this is a greater challenge necessitating the need for more engaging and innovative approaches. The primary aim of this trial is to determine whether a home-based 6-month PA intervention with individual goal-setting and peer mentors (GM-PA) can significantly increase PA levels in insufficiently active older adults at increased risk of developing Alzheimer's disease (AD). METHODS: Community living 60-80 year olds with SMC or MCI who do not engage in more than 60 min per week of moderate intensity PA will be recruited from memory clinics and the community via media advertisements to participate in this randomized, single-blind controlled trial. All participants will receive an individually tailored home-based PA program of 150 min of moderate intensity walking/week for 6 months. The intervention group will undertake individual goal-setting and behavioral education workshops with mentor support via telephone (GM-PA). Those randomized to the control group will have standard education workshops and Physical Activity Liaison (PAL) contact via telephone (CO-PA). Increase in PA is the primary outcome, fitness, cognitive, personality, demographic and clinical parameters will be measured and a health economic analysis performed. A saliva sample will be collected for APOE e4 genotyping. All participants will have a goal-setting interview to determine their PA goals. Active volunteers aged 50-85 years will be recruited from the community randomized and trained to provide peer support as mentors (intervention group) or PALS (control group) for the 6-month intervention. Mentors and PALS will have PA, exercise self-efficacy and mentoring self-efficacy measured. Participants in both groups are asked to attend 3 workshops in 6 months. At the first workshop, they will meet their allocated Mentor or PAL who will deliver their respective programs and support via 6 telephone calls during the intervention. DISCUSSION: If the GM-PA program is successful in increasing the PA levels of the target group it will potentially provide another strategy and community resource that can be translated into practice. TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry ACTRN12613001181796 . (29/10/2013) retrospectively registered.