Cost-effective strategies to maintain healthy active lifestyle in aging populations are required to address the global burden of age-related diseases. ASPREE will examine whether the potential primary prevention benefits of low dose aspirin outweigh the risks in older healthy individuals. Our primary hypothesis is that daily oral 100 mg enteric-coated aspirin will extend a composite primary endpoint termed ‘disability-free life’ including onset of dementia, total mortality, or persistent disability in at least one of the Katz Activities of Daily Living in 19,000 healthy participants aged 65 years and above (‘US minorities’) and 70 years and above (non ‘US minorities’). ASPREE is a double-blind, randomized, placebo-controlled trial of oral 100 mg enteric-coated acetyl salicylic acid (ASA) or matching placebo being conducted in Australian and US community settings on individuals free of dementia, disability and cardiovascular disease (CVD) events. Secondary endpoints are all-cause and cause specific mortality, fatal and non-fatal cardiovascular events, fatal and non-fatal cancer (excluding non-melanoma skin cancer), dementia, mild cognitive impairment, depression, physical disability, and clinically significant bleeding. To 20 September 2013 14383 participants have been recruited. Recruitment and study completion is anticipated in July 2014 and December 2018 respectively. In contrast to other aspirin trials that have largely focused on cardiovascular endpoints, ASPREE has a unique composite primary endpoint to better capture the overall risk and benefit of aspirin to extend healthy independent lifespan in older adults in the US and Australia.

13ecker, RE., J. Colliver, R. Elble, E. Feldman, E. Giacobini, V. Kumar, S. Markwell, P. Moriearty, R. Parks, S.D. Shillcutt, L. Unni, S. Vicari, C. Womack, and R.F. Zec: Effects of metrifonate, a long-acting cholinesterase inhibitor, in Alzheimer disease: Report of an open trial. Drug Dev. Res. 19:425-434, 1990. This is the first study of a multiple-dose trial of metrifonate (Met), a long-acting cholinesterase (ChE) inhibitor, conducted over a prolonged period of time in humans. We have administered Met to 20 patients who met NINCDS-ADRDA criteria for probable Alzheimer disease (AD). Patients were given, under open conditions, single oral doses of Met, 2.5, 5, '7.5, and 15 mgikgiwk. A statistically significant improvement in the Alzheimer Disease Assessment Scale (ADAS) scores was observed with the 5 mgikgiwk dose. Maximal im-Iprovement on the ADAS was associated with a mean 55.9% (2 12.6% standard deviation) ;activity level of red blood cell (RBC) acetylcholinesterase (AChE). Over 80% inhibition of plasma and RBC ChE was achieved with only minor side effects. Cholinesterate inhibition in the CSF of two patients was 37% and 47.5% 24 hr after a second dose of 5 mgikglwk of IMet separated by 7 days from the first dose.Twenty-seven minor side effects were reported: none on 2.5 mg, 5 on 5 mg, 9 on 7.5 mg, and 13 on the 15 mg dose. None of the side effects was clinically significant or drug related or required termination of treatment or dosage adjustment. We conclude that Met is 426 Becker et al.a useful new pharmacological probe of cholinergic function in the central nervous system and that a double-blind evaluation of Met in AD is warranted.

Acetylcholinesterase (AChE; EC 3.1.1.7) is present in both primitive and mature erythroid cells, and a role has been suggested for the enzyme in regulation of differentiation in the human erythron. AChE is also a major enzyme in the central nervous system; alteration of its activity has been proposed as a therapeutic strategy in Alzheimer disease. We recently treated 18 Alzheimer disease patients with metrifonate, a long-acting AChE inhibitor, over periods up to 7 months, with resulting erythrocyte AChE inhibition as high as 82 per cent of baseline values. Despite chronic reduction of enzyme activity, no significant alterations were noted in erythrocyte, leukocyte or platelet characteristics or numbers that would suggest a deleterious effect of AChE inhibition on normal differentiation. Thus, any modification of developmental pathways appears to be compensated by other regulatory mechanisms in the intact organism.

Background: Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB) differ in their memory, attention, and visuoconstructional characteristics. The subscales of the well-known Mini-Mental State Examination (MMSE) provide an opportunity to assess these characteristics. Previous research has shown that analysis of the MMSE subscale performance of AD and DLB patients helps to differentiate them. Objective: Study the MMSE scores of AD and DLB patients to see if the ability of previously reported analyses to differentiate them could be improved. Include other dementia patients for perspective. Methods: We studied the MMSEs of all patients seen in our clinics during an 18-month period. Different equations were studied, derived from the subscales of Memory (M, 3 points maximum), Attention (A, 5 points maximum), and Pentagon-copying (P, 1 point maximum). Results: We obtained 400 MMSEs, 136 from AD patients and 24 from DLB patients, scoring range 1–30. The equation P minus M provided the best discrimination between AD and DLB. Using a P-M score = 1 to identify AD, the positive predictive value was 0.97, negative predictive value 0.22, specificity 0.92, and sensitivity 0.43. As a secondary finding, the P-M = 1 equation was also helpful to differentiate AD from Parkinson’s disease dementia. Conclusion: Considering AD versus DLB in our clinic population, a demented patient who was unable to recall the three memory words on the MMSE but able to copy the intersecting pentagons had a 97% likelihood of having AD. Additional work is needed to improve the sensitivity of the P-M = 1 equation.

No abstract