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1.  Aspirin for the prevention of cognitive decline in the elderly: rationale and design of a neuro-vascular imaging study (ENVIS-ion) 
BMC Neurology  2012;12:3.
Background
This paper describes the rationale and design of the ENVIS-ion Study, which aims to determine whether low-dose aspirin reduces the development of white matter hyper-intense (WMH) lesions and silent brain infarction (SBI). Additional aims include determining whether a) changes in retinal vascular imaging (RVI) parameters parallel changes in brain magnetic resonance imaging (MRI); b) changes in RVI parameters are observed with aspirin therapy; c) baseline cognitive function correlates with MRI and RVI parameters; d) changes in cognitive function correlate with changes in brain MRI and RVI and e) whether factors such as age, gender or blood pressure influence the above associations.
Methods/Design
Double-blind, placebo-controlled trial of three years duration set in two Australian academic medical centre outpatient clinics. This study will enrol 600 adults aged 70 years and over with normal cognitive function and without overt cardiovascular disease. Subjects will undergo cognitive testing, brain MRI and RVI at baseline and after 3 years of study treatment. All subjects will be recruited from a 19,000-patient clinical outcome trial conducted in Australia and the United States that will evaluate the effects of aspirin in maintaining disability-free longevity over 5 years. The intervention will be aspirin 100 mg daily versus matching placebo, randomized on a 1:1 basis.
Discussion
This study will improve understanding of the mechanisms at the level of brain and vascular structure that underlie the effects of aspirin on cognitive function. Given the limited access and high cost of MRI, RVI may prove useful as a tool for the identification of individuals at high risk for the development of cerebrovascular disease and cognitive decline.
Trial Registration
clinicaltrials.gov Identifier: NCT01038583
doi:10.1186/1471-2377-12-3
PMCID: PMC3297524  PMID: 22315948
2.  Arterial Pulse Wave Velocity and Cognition with Advancing Age 
Hypertension  2009;53(4):668-673.
We hypothesized that carotid-femoral pulse wave velocity, a marker of arterial stiffness, interacts with age such that the magnitude of associations between pulse wave velocity and cognitive performance are greater with increasing age, and that this interaction is observed despite adjustments for demographic variables, mean arterial pressure, and cardiovascular risk factors. Pulse wave velocity was estimated using applanation tonometry in 409 dementia- and stroke-free participants of the Maine-Syracuse Longitudinal Study (24 to 92 years of age, 62.3% women). Using linear regression analyses in a cross-sectional design, associations between pulse wave velocity, age, and the interaction of pulse wave velocity and age were examined in relation to a Global composite score, the Wechsler Adult Intelligence Scale Similarities test (abstract reasoning) and four cognitive domains indexed by multiple cognitive measures. Adjusting for age, gender, education, height, weight, heart rate, mean arterial pressure, and antihypertensive treatment, pulse wave velocity by age interactions were obtained for the Global, Visual-Spatial Organization and Memory, Scanning and Tracking, and Verbal Episodic Memory composites, and Similarities. The combination of higher pulse wave velocity and age resulted in progressively lower cognitive performance. This finding was the same with an extended model which also included adjustment for cardiovascular risk factors and other confounds. Pulse wave velocity interacts with age in a multiplicative way to exert a negative influence on cognitive performance level. Early interventions to prevent an increase in arterial stiffness could possibly play an important role in preservation of cognitive ability.
doi:10.1161/HYPERTENSIONAHA.108.126342
PMCID: PMC2716128  PMID: 19237680
pulse wave velocity; hypertension; age; cognitive performance; cognitive functioning; cognition; blood pressure
3.  An action research protocol to strengthen system-wide inter-professional learning and practice [LP0775514] 
Background
Inter-professional learning (IPL) and inter-professional practice (IPP) are thought to be critical determinants of effective care, improved quality and safety and enhanced provider morale, yet few empirical studies have demonstrated this. Whole-of-system research is even less prevalent. We aim to provide a four year, multi-method, multi-collaborator action research program of IPL and IPP in defined, bounded health and education systems located in the Australian Capital Territory (ACT). The project is funded by the Australian Research Council under its industry Linkage Program.
Methods/Design
The program of research will examine in four inter-related, prospective studies, progress with IPL and IPP across tertiary education providers, professional education, regulatory and registration bodies, the ACT health system's streams of care activities and teams, units and wards of the provider facilities of the ACT health system. One key focus will be on push-pull mechanisms, ie, how the education sector creates student-enabled IPP and the health sector demands IPL-oriented practitioners. The studies will examine four research aims and meet 20 research project objectives in a comprehensive evaluation of ongoing progress with IPL and IPP.
Discussion
IPP and IPL are said to be cornerstones of health system reforms. We will measure progress across an entire health system and the clinical and professional education systems that feed into it. The value of multi-methods, partnership research and a bi-directional push-pull model of IPL and IPP will be tested. Widespread dissemination of results to practitioners, policymakers, managers and researchers will be a key project goal.
doi:10.1186/1472-6963-7-144
PMCID: PMC2212639  PMID: 17854507
4.  NAT gene polymorphisms and susceptibility to Alzheimer's disease: identification of a novel NAT1 allelic variant 
Background
Alzheimer's disease is multifactorial, having environmental, toxicological and genetic risk factors. Impaired folate and homocysteine metabolism has been hypothesised to increase risk. In addition to its xenobiotic-metabolising capacity, human arylamine N-acetyltransferase type-1 (NAT1) acetylates the folate catabolite para-aminobenzoylglutamate and is implicated in folate metabolism. The purpose of this study was to determine whether polymorphisms in the human NAT genes influence susceptibility to Alzheimer's disease.
Methods
Elderly individuals with and without Alzheimer's disease were genotyped at the polymorphic NAT1 (147 cases; 111 controls) and NAT2 (45 cases; 63 controls) loci by polymerase chain reaction-restriction fragment length polymorphism, and the genotype and allele frequencies were compared using the chi-squared test.
Results
Although a trend towards fast NAT2 acetylator-associated Alzheimer's disease susceptibility was indicated and the NAT1*10/1*10 genotype was observed only in cases of Alzheimer's disease (6/147, 4.1%), no significant difference in the frequency of NAT2 (p = 0.835) or NAT1 (p = 0.371) genotypes was observed between cases and controls. In addition, a novel NAT1 variant, NAT1*11B, was identified.
Conclusions
These results suggest that genetic polymorphisms in NAT1 and NAT2 do not influence susceptibility to Alzheimer's disease, although the increase in frequency of the NAT1*10 allele in Alzheimer's disease is worthy of further investigation. Due to its similarity with the NAT1*11A allele, NAT1*11B is likely to encode an enzyme with reduced NAT1 activity.
doi:10.1186/1471-2350-5-6
PMCID: PMC395831  PMID: 15142281

Results 1-4 (4)