Alzheimer Disease: Sanders L

Brickman AM, Honig LS, Scarmeas N, Tatarina O, Sanders L, Albert MS, Brandt J, Blacker D, Stern Y. · Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, 630 W 168th St, Campus Box 16, New York, NY 10032, USA. · Arch Neurol. · Pubmed #18779424 No free full text.

Abstract: OBJECTIVE: To determine if baseline measurements of cerebral atrophy and severity of white matter hyperintensity (WMH) predict the rate of future cognitive decline in patients with Alzheimer disease (AD). DESIGN: Data were drawn from the Predictors Study, a longitudinal study that enrolls patients with mild AD and reassesses them every 6 months with use of the Columbia modified Mini-Mental State (mMMS) examination (score range, 0-57). Magnetic resonance images were analyzed to determine the severity of WMH, using the Scheltens scale, and the degree of atrophy, using the bicaudate ratio. Generalized estimating equations were used to determine whether severity of baseline magnetic resonance image measurements and their interaction predicted the rate of mMMS score decline at subsequent visits. SETTING: Three university-based AD centers in the United States. PARTICIPANTS: At baseline, 84 patients with AD from the Predictors Study received structural magnetic resonance imaging and were selected for analysis. They had a mean of 6 follow-up evaluations. Main Outcome Measure The mMMS score. RESULTS: Generalized estimating equation models demonstrated that the degree of baseline atrophy (beta = -0.316; P = .04), the severity of WMH (beta = -0.173; P = .03), and their interaction (beta = -6.061; P = .02) predicted the rate of decline in mMMS scores. CONCLUSIONS: Both degree of cerebral atrophy and severity of WMH are associated with the rapidity of cognitive decline in AD. Atrophy and WMH may have a synergistic effect on future decline in AD, such that patients with a high degree of both have a particularly precipitous cognitive course. These findings lend further support to the hypothesis that cerebrovascular pathological abnormalities contribute to the clinical syndrome of AD.

Granholm AC, Sanders L, Seo H, Lin L, Ford K, Isacson O. · Department of Physiology and Neuroscience and the Center on Aging, Medical University of South Carolina, Charleston, South Carolina 29425, USA. · Hippocampus. · Pubmed #14750653 No free full text.

Abstract: Individuals with Down syndrome (DS) develop the pathological hallmarks of Alzheimer's disease at an early age, later followed by memory decline and dementia. Women with DS are twice as likely to undergo early menopause, and levels of estradiol correlate with onset of cognitive decline in these women. We have demonstrated that a mouse model of DS, mice with segmental trisomy of chromosome 16 (Ts65Dn), develop a significant deficit in both reference and working memory as young adults (6-10 months of age), coupled with phenotypic loss of cholinergic neurons in the basal forebrain and altered growth factor levels. In the present study we examined cholinergic and dendritic markers in the hippocampal formation and levels of the amyloid precursor protein (APP) in different brain regions of Ts65Dn mice treated with estradiol for 60 days. The density of the dendritic marker Map2 was significantly decreased in the hippocampal formation of middle-aged trisomic mice (9-15 months old), and the density of cholinergic neurites (acetylcholinesterase [AChE] histochemistry) was also decreased in specific layers of the hippocampus. Treatment with 17beta-estradiol alleviated the decreases in Map2 and AChE staining, but had no effect on full-length APP levels in the hippocampus. In contrast, a main effect of treatment on APP levels in the striatum was noted, with significant elevations observed in controls and trisomics. These findings demonstrate that estrogen can alleviate deficits in cholinergic and dendritic elements in the hippocampal formation and further strengthens the rationale to explore estrogen replacement therapy in women with DS.