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Authors: Cross, Amanda J. | George, Johnson | Woodward, Michael C. | Ames, David | Brodaty, Henry | Wolfe, Rory | Connors, Michael H. | Elliott, Rohan A.

Article Type: Research Article

Abstract: Background: There is limited evidence regarding the association between potentially inappropriate medications (PIM) and mortality in older people with cognitive impairment. Objective: To examine whether use of medications considered to be potentially inappropriate in older people with cognitive impairment (PIMcog) and anticholinergic cognitive burden (ACB) were associated with mortality in people who attended memory clinics. Methods: Cross-sectional and longitudinal analyses of data from the Prospective Research In MEmory clinics (PRIME) study. Participants were community-dwelling people who attended nine memory clinics and had a diagnosis of mild cognitive impairment or dementia. PIMcog was defined as any medication considered potentially inappropriate for …a person with cognitive impairment according to Beers or STOPP criteria. Anticholinergic burden was calculated using the ACB scale. Time-dependent Cox-proportional hazards regression was used to analyze associations between PIMcog use/ACB score and all-cause mortality over a three-year follow-up period. The regression model included the baseline variables: age, gender, education, cognitive diagnoses, total number of medications, disease-burden, cognition, physical function, and neuropsychiatric symptoms. Results: Of 964 participants, 360 (37.3%) used one or more PIMcog at some time during the study; most commonly anticholinergics and sedatives. 624 (64.7%) participants used a medication with potential or definite anticholinergic properties (ACB>0) at some point during the study. Both PIMcog use (adjusted hazard ratio: 1.42 95% CI: 1.12–1.80) and ACB score (adjusted hazard ratio: 1.18 95% CI: 1.06–1.32) were associated with mortality. Conclusion: Use of PIMcogs and medications with anticholinergic properties was common among memory clinic patients and both were associated with mortality. Show more

Keywords: Alzheimer’s disease, cholinergic antagonists, cognitive dysfunction, dementia, inappropriate prescribing, mortality, potentially inappropriate medication list, contstartabstract

DOI: 10.3233/JAD-170265

Citation: Journal of Alzheimer's Disease, vol. 60, no. 2, pp. 349-358, 2017

Authors: Brodaty, Henry | Connors, Michael H. | Xu, Jing | Woodward, Michael | Ames, David | on behalf of the PRIME study group

Article Type: Research Article

Abstract: Patients with dementia often require institutionalization when they can no longer care for themselves. The study examined demographic and clinical variables that predict the time until institutionalization in patients with dementia attending memory clinics. Of 970 patients recruited from nine memory clinics around Australia, 779 patients had dementia at baseline. Measures of dementia severity, cognition, functional ability, neuropsychiatric symptoms, caregiver burden, and medication use were completed for all patients. Patients were followed for three years. Overall, 197 (25.3%) of the patients with dementia were institutionalized within three years. Lower cognitive ability, lower functional ability, and more neuropsychiatric symptoms at baseline …predicted a shorter time until institutionalization, as did use of antipsychotic medication. In addition, greater deterioration in cognitive ability, functional ability, and neuropsychiatric symptoms over the initial three months predicted a shorter time to institutionalization. The findings confirm that clinical features of dementia at baseline predict the time to institutionalization, as do greater changes in symptoms over three months independent of baseline levels. Show more

Keywords: Alzheimer's disease, dementia, institutionalization, longitudinal, nursing home, survival analysis

DOI: 10.3233/JAD-131850

Citation: Journal of Alzheimer's Disease, vol. 40, no. 1, pp. 221-226, 2014

Authors: Connors, Michael H. | Ames, David | Boundy, Karyn | Clarnette, Roger | Kurrle, Sue | Mander, Alastair | Ward, John | Woodward, Michael | Brodaty, Henry

Article Type: Research Article

Abstract: Background: Dementia is a terminal illness. While various baseline characteristics of patients, such as age, sex, and dementia severity, are known to predict mortality, little research has examined how changes in patients’ symptoms over time predict survival. There are also limited data on patients seen in memory clinics, as opposed to other health care settings, and whether antipsychotic medications are associated with mortality in dementia once patients’ demographic and clinical features are controlled for. Objective: To identify predictors of mortality in patients with dementia. Method: Of 970 patients recruited from nine memory clinics around Australia, 779 patients had dementia at …baseline. Patients completed measures of dementia severity, cognition, functional ability, neuropsychiatric symptoms, caregiver burden, and medication use at baseline and at regular intervals over a three-year period. Mortality data were obtained from state registries eight years after baseline. Results: Overall, 447 (57.4%) of the patients with dementia died within the eight years. Older age, male sex, more severe dementia and functional impairment at baseline, greater decline in dementia severity and functional impairment over six months, taking a larger number of medications, and use of atypical antipsychotic medication predicted earlier mortality. Conclusions: The findings confirm that demographic and diagnostic features predict the survival of patients with dementia. Importantly, the findings indicate that changes in dementia severity and functional impairment over time predict mortality independently of baseline levels, and provide further evidence for the higher mortality risk of patients taking antipsychotic medications. Show more

Keywords: Death, dementia, longitudinal study, mortality, predictors

DOI: 10.3233/JAD-150946

Citation: Journal of Alzheimer's Disease, vol. 52, no. 3, pp. 967-974, 2016

Authors: Connors, Michael H. | Ames, David | Boundy, Karyn | Clarnette, Roger | Kurrle, Sue | Mander, Alastair | Ward, John | Woodward, Michael | Brodaty, Henry

Article Type: Research Article

Abstract: Background: Patients with mild cognitive impairment (MCI) are at greater risk of mortality than the general population. Comparatively little research has examined predictors of mortality in MCI and no research has examined whether time-varying variables, such as change in cognition and function, predict survival. Objective: To identify predictors of mortality in patients with MCI. Methods: 185 patients with MCI were recruited from nine memory clinics around Australia. Patients completed measures of cognition, function, and neuropsychiatric symptoms over three years. Mortality data were obtained from state registries eight years after baseline. Results: 55 (30%) patients died within this period. Older age, …lower cognitive and functional ability at baseline, and greater decline in functional ability over six months predicted mortality. Conclusion: Easily measurable clinical data predict mortality in patients with MCI. Longitudinal assessment over time can provide additional information about patients’ risk. Show more

Keywords: Lifespan, longitudinal studies, mild cognitive impairment, mortality, risk factors, survival

DOI: 10.3233/JAD-160148

Citation: Journal of Alzheimer's Disease, vol. 54, no. 1, pp. 149-155, 2016

Authors: Kinsella, Glynda J. | Ames, David | Storey, Elsdon | Ong, Ben | Pike, Kerryn E. | Saling, Michael M. | Clare, Linda | Mullaly, Elizabeth | Rand, Elizabeth

Article Type: Research Article

Abstract: Background: Governments are promoting the importance of maintaining cognitive health into older age to minimize risk of cognitive decline and dementia. Older people with amnestic mild cognitive impairment (aMCI) are particularly vulnerable to memory challenges in daily activities and are seeking ways to maintain independent living. Objective: To evaluate the effectiveness of memory groups for improving memory strategies and memory ability of older people, especially those with aMCI. Methods: 113 healthy older adults (HOA) and 106 adults with aMCI were randomized to a six-week memory group or a waitlist control condition. Outcome was evaluated through knowledge and use of memory …strategies, memory ability (self-report and neuropsychological tests), and wellbeing. Assessments included a six-month follow-up. Results: Using intention to treat analyses, there were intervention effects for HOA and aMCI groups in strategy knowledge (HOA: η 2 = 0.20; aMCI: η 2 = 0.06), strategy use (HOA: η 2 = 0.18; aMCI: η 2 = 0.08), and wellbeing (HOA: η 2 = 0.11; aMCI: η 2 = 0.05). There were also intervention effects in the HOA group, but not the aMCI group, in self-reported memory ability (η 2 = 0.06) and prospective memory tests (η 2 = 0.02). By six-month follow-up, gains were found on most HOA outcomes. In the aMCI group gains were found in strategy use, and by this stage, gains in prospective memory were also found. Conclusion: Memory groups can engage older people in techniques for maintaining cognitive health and improve memory performance, but more modest benefits are seen for older adults with aMCI. Show more

Keywords: Aging, memory, memory training, mild cognitive impairment, prospective memory, randomized controlled trial

DOI: 10.3233/JAD-150378

Citation: Journal of Alzheimer's Disease, vol. 49, no. 1, pp. 31-43, 2016

Authors: Brown, Belinda M. | Rainey-Smith, Stephanie R. | Dore, Vincent | Peiffer, Jeremiah J. | Burnham, Samantha C. | Laws, Simon M. | Taddei, Kevin | Ames, David | Masters, Colin L. | Rowe, Christopher C. | Martins, Ralph N. | Villemagne, Victor L.

Article Type: Research Article

Abstract: Numerous animal studies have reported exercise reduces the accumulation of Alzheimer’s disease pathology, including amyloid-β (Aβ) and tau. Furthermore, we previously reported a relationship between higher levels of physical activity (PA) and lower brain Aβ burden in a human population. The recent advent of tau positron emission tomography (PET) tracers enables us to extend our investigations into the evaluation of the relationship between PA and brain tau burden. Utilizing data from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study, we have examined the cross-sectional relationship between habitual PA and PET-quantified tau burden. Forty-three cognitively healthy older adults were categorized into …low-moderate PA (LMPA; n  = 16) or high PA (HPA; n  = 27), based on self-reported PA levels. Tau PET imaging with the AV1451 tracer was conducted on all participants. The LMPA group had significantly higher neocortical tau burden (presented as a z-score; 1.22±1.98), compared to the HPA group (z-score: – 0.28±1.18). The difference between the LMPA and HPA groups was also evident when examining regional tau burden in the temporoparietal cortex and the prefrontal cortex. Our results suggest an association between self-reported PA level and brain tau burden. Future longitudinal and interventional studies utilizing larger samples sizes are vital to further investigate the nature of the relationship between tau and PA. Show more

Keywords: Alzheimer’s disease, physical activity, positron emission tomography, tau

DOI: 10.3233/JAD-170998

Citation: Journal of Alzheimer's Disease, vol. 63, no. 4, pp. 1299-1305, 2018

Authors: Baker, Jenalle E. | Lim, Yen Ying | Jaeger, Judith | Ames, David | Lautenschlager, Nicola T. | Robertson, Joanne | Pietrzak, Robert H. | Snyder, Peter J. | Villemagne, Victor L. | Rowe, Christopher C. | Masters, Colin L. | Maruff, Paul

Article Type: Research Article

Abstract: Recent meta-analyses suggest that episodic memory impairment associated with preclinical Alzheimer’s disease (AD) equates to 0.15–0.24 standard deviations below that of cognitively healthy older adults. The current study aimed to characterize impairments in verbal acquisition and recall detectable at a single assessment, and investigate how verbal learning and episodic memory deteriorates in preclinical AD. A verbal list-learning task, the International Shopping List Test (ISLT), was administered multiple times over an 18-month period, to three groups of participants: amyloid-beta negative healthy older adults (Aβ – CN; n  = 50); Aβ + positive healthy older adults (preclinical AD; n  = 25); and Aβ + …positive individuals diagnosed with mild cognitive impairment (prodromal AD; n  = 22). At baseline, there was no significant difference between the preclinical AD and control groups rate of acquisition, or total and delayed recall, however all indices were impaired in prodromal AD. Performance on ISLT total score improved in the control group over the 18-month period, but showed a moderate magnitude decline in the preclinical AD group (Cohen’s d  = – 0.63, [– 1.12, – 0.14]) and the prodromal AD group (Cohen’s d  = – 0.36, [– 0.94, 0.22]). No significant impairment in acquisition associated with preclinical AD was seen at baseline. Individuals with preclinical AD showed a significantly different performance on the ISLT total score over an 18-month period, compared to those without abnormal Aβ . Individuals with prodromal AD showed substantial impairment on the ISLT at baseline and declined to a greater extent over time. Show more

Keywords: Alzheimer’s disease, amyloid-β protein, cognitive decline, learning curve, memory and learning tests, mild cognitive impairment, neuropsychology, transfer of learning

DOI: 10.3233/JAD-180344

Citation: Journal of Alzheimer's Disease, vol. 65, no. 3, pp. 977-988, 2018

Authors: Yassi, Nawaf | Hilal, Saima | Xia, Ying | Lim, Yen Ying | Watson, Rosie | Kuijf, Hugo | Fowler, Christopher | Yates, Paul | Maruff, Paul | Martins, Ralph | Ames, David | Chen, Christopher | Rowe, Christopher C. | Villemagne, Victor L. | Salvado, Olivier | Desmond, Patricia M. | Masters, Colin L.

Article Type: Research Article

Abstract: Background: Quantifying the contribution of cerebrovascular disease to the clinical and pathological profile of Alzheimer’s disease is challenging. Objective: We aimed to determine the influence of cerebrovascular disease, amyloid-β (Aβ), and their comorbidity on cognitive decline, hippocampal atrophy, and Aβ deposition, by evaluating data from the Australian Imaging, Biomarker and Lifestyle Study of Ageing. Methods: Two-hundred and eighteen participants underwent Aβ PET, MRI, and cognitive assessment at 18-month intervals for up to 90 months. Aβ status was determined on baseline PET. Participants were also classified as V+ on baseline MRI if they had≥1 large cortical infarcts, subcortical infarcts, or cortical …cerebral microinfarcts; or white matter hyperintensity volume greater than the 90th percentile of healthy controls. Linear mixed models were conducted comparing slopes of change in cognition, hippocampal volume, and Aβ load between the four resultant groups. Results: Mean age at baseline was 74 years (range 59–96). One-hundred and fifteen participants were cognitively normal, 54 had mild cognitive impairment, and 49 had Alzheimer’s disease. Compared to the Aβ-/V- group, the Aβ+/V- and Aβ+/V+ groups showed significantly faster cognitive decline and hippocampal atrophy over 90 months. V + status was associated with greater cognitive decline (Cohen’s d  = 0.85, p  < 0.001) and hippocampal atrophy (d  = 2.05, p  < 0.001) in the Aβ+ group but not in the Aβ- group. V+ status was not associated with Aβ accumulation in any group. Conclusion: Comorbidity of cerebrovascular disease and Aβ was associated with cognitive decline and neurodegeneration. Cerebrovascular disease was not associated with the rate of Aβ accumulation. Show more

Keywords: Alzheimer’s disease, cerebrovascular disease, magnetic resonance imaging, mild cognitive impairment, positron emission tomography, stroke

DOI: 10.3233/JAD-191028

Citation: Journal of Alzheimer's Disease, vol. 73, no. 3, pp. 897-907, 2020

Authors: Lai, Michelle M.Y. | Sharman, Matthew J. | Ames, David J. | Ellis, Kathryn A. | Cox, Kay L. | Hepworth, Graham | Desmond, Patricia | Cyarto, Elizabeth V. | Martins, Ralph N. | Masters, Colin L. | Lautenschlager, Nicola T.

Article Type: Research Article

Abstract: Background: There is a paucity of information on the role of microvascular and inflammatory biomarkers in cognitive dysfunction. Objective: This study sought to evaluate the relationships between established and a number of peripheral biomarkers on cognitive patterns in 108 older adults with memory complaints. Methods: Participants in the AIBL Active study aged 60 years and older with at least one vascular risk factor and memory complaints completed a neuropsychological test battery and provided cross-sectional health data. Linear regression models adjusted for covariates examined associations between cognitive performance and a panel of vascular risk factors (Framingham cardiovascular scores, hs-CRP, homocysteine, fasting …glucose, LDL-cholesterol) and peripheral biomarkers (TNF-α , BDNF, VCAM-1, ICAM-1, PAI-1, CD40L). Results: Higher fasting glucose and homocysteine levels were independent factors associated with poorer performance in Trail Making Test (TMT) B (adjusted β= 0.40±0.10 and 0.43±0.09, respectively). Increasing homocysteine levels were weakly associated with poorer global cognition and delayed recall (adjusted β= 0.23±0.10 and –0.20±0.10 respectively). Increasing Framingham cardiovascular scores were related to poorer performance in TMT B (β  = 0.42±0.19). There was early evidence of associations between increasing plasma TNF-α and poorer TMT B (adjusted β  = 0.21±0.10) and between increasing BDNF and better global cognition (β= –0.20±0.09). Conclusion: This study provides evidence to support the associations between vascular risk factors (Framingham scores, fasting glucose, and homocysteine) and poorer cognitive functions. Additionally, we measured several peripheral biomarkers to further investigate their associations with cognition. The relationship between TNF-α , BDNF, and cognitive performance in various domains may offer new insights into potential mechanisms in vascular cognitive impairment. Show more

Keywords: BDNF, biomarkers, cardiovascular disease, cognitive impairment, homocysteine, TNF-α, vascular risk factors, Trial Registration: Australia New Zealand Clinical Trials Registry ACTRN126110006129

DOI: 10.3233/JAD-190953

Citation: Journal of Alzheimer's Disease, vol. 74, no. 1, pp. 163-171, 2020

Authors: Cox, Kay L. | Cyarto, Elizabeth V. | Ellis, Kathryn A. | Ames, David | Desmond, Patricia | Phal, Pramit | Sharman, Matthew J. | Szoeke, Cassandra | Rowe, Christopher C. | Masters, Colin L. | You, Emily | Burrows, Sally | Lai, Michelle M.Y. | Lautenschlager, Nicola T.

Article Type: Research Article

Abstract: 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. Show more

Keywords: Adherence, cerebrovascular disease, mild cognitive impairment, physical activity, subjective memory complaints

DOI: 10.3233/JAD-180521

Citation: Journal of Alzheimer's Disease, vol. 70, no. s1, pp. S187-S205, 2019