Alzheimer Disease: Berg JD

Aisen PS, Berg JD, Craft S, Peskind ER, Sano M, Teri L, Mulnard RA, Thomas RG, Thal LJ. · Department of Neurology, Georgetown University Medical Center, 1Bles Building, 3800 Reservoir Road NW, Washington, DC 20007, USA. · Psychoneuroendocrinology. · Pubmed #12445840 No free full text.

Abstract: Glucose and insulin may play an important role in the pathophysiology and symptomatology of Alzheimers disease (AD), and prior studies suggest interactions among glucose, insulin, gender and apolipoprotein E genotype. We analyzed the relationship between steroid-induced glucose elevation and gender, presence of the apolipoprotein E epsilon 4 (APOE-4) allele and cognition using data from a multicenter trial of prednisone therapy in AD. The low-dose prednisone regimen (initial dose: 20 mg/day, maintenance dose: 10 mg/day) caused a moderate increase in random blood glucose (mean post-baseline glucose 115 mg/dl). There was a significant interaction between rise in glucose, gender and presence of the APOE-4 allele. There was no important relationship between glucose and cognitive function at baseline or with prednisone treatment. Meta-analysis including data from three other AD trials showed a small influence of random blood glucose on cognitive scores. These results support a relationship between gender, apolipoprotein E genotype and glucose metabolism, but do not indicate that mild changes in glucose have an important impact on cognitive function.

Aisen PS, Davis KL, Berg JD, Schafer K, Campbell K, Thomas RG, Weiner MF, Farlow MR, Sano M, Grundman M, Thal LJ. · Department of Neurology, Georgetown University Medical Center, Washington, DC 20007, USA. · Neurology. · Pubmed #10680787 No free full text.

Abstract: BACKGROUND: Laboratory and epidemiologic studies suggest that anti-inflammatory/immunosuppressive therapy may be useful in the treatment of AD. In preliminary studies, a regimen of low to moderate dose prednisone was found to suppress peripheral inflammatory markers without adverse effects in subjects with AD. METHODS: We conducted a randomized, placebo-controlled multicenter trial to determine whether prednisone treatment slowed the rate of cognitive decline in AD. The active treatment regimen consisted of an initial dose of 20 mg of prednisone daily for 4 weeks tapered to a maintenance dose of 10 mg daily for 1 year, followed by gradual withdrawal during an additional 16 weeks. The primary outcome measure was the 1-year change in the cognitive subscale of the AD Assessment Scale. RESULTS: A total of 138 subjects were randomized to the drug and placebo groups. There was no difference in cognitive decline between the prednisone and placebo treatment groups in the primary intent-to-treat analysis, or in a secondary analysis considering completers only. Subjects treated with prednisone showed behavioral decline compared with those in the placebo group. CONCLUSION: A low-dose regimen of prednisone is not useful in the treatment of AD.

Thomas RG, Berg JD, Sano M, Thal L. · Alzheimer's Disease Co-operative Study, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0949, USA. · Stat Med. · Pubmed #10844708 No free full text.

Abstract: Evidence of delayed progression is the primary mechanism for demonstrating therapeutic efficacy in clinical trials in Alzheimer's disease. In the major trials of therapeutic treatment of AD, to date, measures based on clinical judgement and cognitive performance, instead of mortality, have been used as the primary response measures. There is good reason for this since the course of the disease is quite long, and AD trials designed around mortality would require either very large sample sizes or very long follow-up in order to have adequate power. However, the evaluation of progression in AD using clinical markers is subject to a number of challenges often found in longitudinal databases, for example, missing data, floor and ceiling effects and non-linearity. Unfortunately, few of these issues are being addressed in the typical analysis of progression data. This paper explores these analytic issues in the context of the recently completed Alzheimer's Disease Cooperative Study trial of vitamin E and Selegeline in moderate AD patients.