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OBJECTIVE:To determine the influence of apolipoprotein E on cognitive decline in a cohort of elderly men and women. DESIGN: Prospective study. SETTING: Scotland, Ireland, and the Netherlands. PARTICIPANTS: Five thousand eight hundred four subjects aged 70 to 82 from the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER). MEASUREMENTS: Subjects were assessed at baseline and over a mean 3.2-year (range 0.7-4.2) follow-up for memory (Picture-Word Recall), speed of information processing (Stroop and Letter-Digit Coding), global cognitive function (Mini-Mental State Examination), and activities of daily living. RESULTS: At baseline, subjects with apolipoprotein E 4 versus those without E 4 had poorer memory performance (mean score difference À 0.20 (95% confidence interval (CI) 5 À 0.31 to À 0.09) for immediate recall and À 0.32 (95% CI 5 À 0.48 to À 0.16) for delayed recall and slower information processing (difference in Stroop, 2.79 seconds, (95% CI 5 1.20-4.28); Letter-Digit score, À 0.36, (95% CI 5 À 0.77-0.05). Subjects with apolipoprotein E 4 showed a greater decline in immediate ( À 0.22, 95% CI 5 À 0.33 to À 0.11) and delayed ( À 0.30, 95% CI 5 À 0.46 to À 0.15) memory scores but no significant change in speed of information processing (Stroop, P 5.17; Letter-Digit, P 5.06). Memory scores decreased 2.5% from baseline in those without E 4 , 4.3% in E 4 heterozygotes (P 5.01 for immediate and P 5.03 for delayed, vs no E 4 ) and 8.9% to 13.8% in E 4 homozygotes (P 5.04 for immediate and P 5.004 for delayed, vs heterozygotes). Apolipoprotein E 4 was associated with greater decline in instrumental activities of daily living (Po.001). Cognitive decline was not associated with lipoprotein levels. CONCLUSION: Findings in PROSPER indicate that E 4 is associated with more-rapid cognitive decline and may, therefore, predispose to dementia. J Am Geriatr Soc 55:1777-1785, 2007. Key words: memory; dementia; trial; statin A major challenge in the quest to promote healthy aging is to uncover the determinants of cognitive decline in the general population and the risk factors that lead to the development of frank dementia. Although age is the main predictor of cognitive function, investigators have also reported that a history of hypertension, diabetes mellitus, stroke, depression, and lack of physical activity are factors. [1][2][3][4][5][6] The apolipoprotein E phenotype (apolipoprotein E is coded by a gene (e) that exhibits allelic variants e 2 , e 3 , and e 4 ) has been linked consistently and strongly to the appearance of Alzheimer's disease and to some aspects of cognitive decline in elderly cohorts. 1,2,[5][6][7][8][9] Inheritance of E 4 (the product of e 4 ) especially in the homozygous form, has been associated in cross-sectional studies with risk of Alzheimer's disease and poorer global cognitive function, episodic memory, and executive function, although the magnitude of the effect is modest. 10,11 Longitudinal data also show good evidence of an association between E 4 and risk of Alzheimer's diseas...

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for the PROSPER Study GroupBackground-The role of C-reactive protein (CRP) in predicting vascular events and response to statin therapy remains uncertain. Additional large prospective studies are required. Methods and Results-Baseline CRP was related to risk over 3.2 years for primary a combined end point (definite or suspected death from coronary heart disease, nonfatal myocardial infarction, and fatal or nonfatal stroke; nϭ865 events) and secondary (coronary heart disease events or stroke alone) and tertiary (stroke plus transient ischemic attack) end points in the

Background-Statins are important in vascular disease prevention in the elderly. However, the best method of selecting older patients for treatment is uncertain. We assessed the role of plasma lipoproteins as predictors of risk and of treatment benefit in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). Method and Results-The association of LDLc and HDLc with risk was examined in the 5804 70-to 82-year-old subjects of PROSPER. Baseline LDLc showed no relation to risk of the primary end point in the placebo group (Pϭ0.27), nor did on-treatment LDLc in the pravastatin group (Pϭ0.12). HDLc was inversely associated with risk in subjects on placebo (Pϭ0.0019) but not in those on pravastatin (Pϭ0.24). Risk reduction on pravastatin treatment was unrelated to baseline LDLc (Pϭ0.38) but exhibited a significant interaction with HDLc (Pϭ0.012

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Abnormalities at cerebral proton spectroscopy occur in patients with the acquired immunodeficiency syndrome (AIDS). N-acetyl aspartate (NAA) is believed to be a neuronal marker, and neuronal loss is thought to underlie the human immunodeficiency virus (HIV)-associated cognitive/motor complex. The proton spectra in 103 HIV-seropositive patients and 23 control subjects were compared and correlated with clinical, immunologic, and radiologic measures of HIV infection. Significant (P < .05) reductions in the mean NAA/choline (Cho) and NAA/creatine (Cr) ratios were seen in patients with immune suppression and neurologic signs. Significant increases in the Cho/Cr ratios were seen in patients with low CD4 lymphocyte counts and abnormal magnetic resonance (MR) images. Reduced NAA ratios correlated with diffuse but not focal MR imaging abnormalities. Combined MR imaging and spectroscopy provides closer relationships to clinical and immunologic measures of disease than either modality alone. Spectroscopy is an adjunct to MR imaging and augments the value of an MR imaging study.

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